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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1135/ | vMOr8p4 | Primary Congenital Glaucoma | C1533041 | 17 | primary congenital glaucoma. 4.2% of all childhood blindness In Saudi Arabia and in the Rom population of Slovakia, PCG is the most common cause of childhood blindness .Differential DiagnosisA number of congenital ocular conditions can mimic PCG and must be considered by the clinician . For example, the nonspecific findings of tearing and redness of the eyes may mimic more common conditions such as conjunctivitis or congenital nasolacrimal duct obstruction; ocular irritation with photophobia and redness may mimic the more frequent problem of corneal abrasion.Congenital glaucoma can be subcategorized by age of onset into the following three types:Primary "newborn"-type congenital glaucoma. The most severe type; clinically apparent between birth and age one monthPrimary "infantile" glaucoma (or infantile PCG) as described by Walton & Katsavounidou . Clinically recognized between age one month and two years"Juvenile" ("late-recognized") primary infantile | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1135/ | vMOr8p4 | Primary Congenital Glaucoma | C1533041 | 17 | primary congenital glaucoma. may mimic the more frequent problem of corneal abrasion.Congenital glaucoma can be subcategorized by age of onset into the following three types:Primary "newborn"-type congenital glaucoma. The most severe type; clinically apparent between birth and age one monthPrimary "infantile" glaucoma (or infantile PCG) as described by Walton & Katsavounidou . Clinically recognized between age one month and two years"Juvenile" ("late-recognized") primary infantile glaucoma. Onset clinically apparent after age two yearsThe types do not correlate with a specific genetic cause, although primary "newborn"-type congenital glaucoma is more likely to be caused by mutation of CYP1B1 than the other types of congenital glaucoma in some populations.In the older child with juvenile onset, or in less severely affected individuals, the increase in intraocular pressure (IOP) is gradual; thus, corneal edema and opacity may be less obvious than in the newborn type. | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1135/ | vMOr8p4 | Primary Congenital Glaucoma | C1533041 | 17 | primary congenital glaucoma. -recognized") primary infantile glaucoma. Onset clinically apparent after age two yearsThe types do not correlate with a specific genetic cause, although primary "newborn"-type congenital glaucoma is more likely to be caused by mutation of CYP1B1 than the other types of congenital glaucoma in some populations.In the older child with juvenile onset, or in less severely affected individuals, the increase in intraocular pressure (IOP) is gradual; thus, corneal edema and opacity may be less obvious than in the newborn type. Progressive enlargement of the globe or "buphthalmos" usually does not occur after age three to four years .Conditions/syndromes associated with infantile glaucoma. A number of well-recognized conditions and syndromes may present with infantile glaucoma, along with other ocular and/or systemic findings. Some conditions may not be compatible with life (e.g., trisomy 13, trisomy 18, Walker-Warburg syndrome, and Zellweger Syndrome); others may be | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1135/ | vMOr8p4 | Primary Congenital Glaucoma | C1533041 | 17 | primary congenital glaucoma. than in the newborn type. Progressive enlargement of the globe or "buphthalmos" usually does not occur after age three to four years .Conditions/syndromes associated with infantile glaucoma. A number of well-recognized conditions and syndromes may present with infantile glaucoma, along with other ocular and/or systemic findings. Some conditions may not be compatible with life (e.g., trisomy 13, trisomy 18, Walker-Warburg syndrome, and Zellweger Syndrome); others may be less severe or confined only to the eye.It is important to establish the diagnosis of an associated syndrome because of the implications for genetic counseling and treatment (see Table 2).Table 2. Conditions/Syndromes Associated with Infantile GlaucomaView in own windowDisorderGene(s)MOIClinical FeaturesEye FindingsOtherAniridiaPAX6WT1 1ADComplete or partial iris hypoplasia w/associated foveal hypoplasia, resulting in reduced visual acuity & nystagmus | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1135/ | vMOr8p4 | Primary Congenital Glaucoma | C1533041 | 17 | primary congenital glaucoma. Syndrome); others may be less severe or confined only to the eye.It is important to establish the diagnosis of an associated syndrome because of the implications for genetic counseling and treatment (see Table 2).Table 2. Conditions/Syndromes Associated with Infantile GlaucomaView in own windowDisorderGene(s)MOIClinical FeaturesEye FindingsOtherAniridiaPAX6WT1 1ADComplete or partial iris hypoplasia w/associated foveal hypoplasia, resulting in reduced visual acuity & nystagmusPresents in early infancyFrequently associated w/other ocular abnormalities, often of later onset, incl cataract, glaucoma, & corneal opacification& vascularization
May occur either as an isolated ocular abnormality w/out systemic involvement or as part of WAGR syndrome 1Anterior segment dysgenesis syndromes(e.g., Peters Plus syndrome)See footnote 2Phenotypically & genotypically distinct from PCG in | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1135/ | vMOr8p4 | Primary Congenital Glaucoma | C1533041 | 17 | primary congenital glaucoma. visual acuity & nystagmusPresents in early infancyFrequently associated w/other ocular abnormalities, often of later onset, incl cataract, glaucoma, & corneal opacification& vascularization
May occur either as an isolated ocular abnormality w/out systemic involvement or as part of WAGR syndrome 1Anterior segment dysgenesis syndromes(e.g., Peters Plus syndrome)See footnote 2Phenotypically & genotypically distinct from PCG in general, but severe or advanced PCG can be difficult to distinguish clinically from some of the anterior segment dysgenesis syndromes; e.g., Peters anomalyPeters Plus syndrome: developmental delay, mild to severe ID, cleft lip, cleft palateAxenfeld-Rieger anomaly (anterior segment disorder)FOXC1PITX2ADPresents w/posterior embryotoxon & (variably) iris strands adherent to Schwalbe' | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1135/ | vMOr8p4 | Primary Congenital Glaucoma | C1533041 | 17 | primary congenital glaucoma. ally distinct from PCG in general, but severe or advanced PCG can be difficult to distinguish clinically from some of the anterior segment dysgenesis syndromes; e.g., Peters anomalyPeters Plus syndrome: developmental delay, mild to severe ID, cleft lip, cleft palateAxenfeld-Rieger anomaly (anterior segment disorder)FOXC1PITX2ADPresents w/posterior embryotoxon & (variably) iris strands adherent to Schwalbe's line, iris hypoplasia, focal iris atrophy, & ectropion uveae.Glaucoma develops in ~50% of affected individuals but is more common in those w/central iris changes & marked anterior iris insertionAlways bilateral, but may be distinctly asymmetric
May occur in the setting of Axenfeld-Rieger syndrome (OMIM 180500): dysmorphic features, dental anomalies, sensorineural hearing loss, cardiac malformations, endocrine & | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1135/ | vMOr8p4 | Primary Congenital Glaucoma | C1533041 | 17 | primary congenital glaucoma. adherent to Schwalbe's line, iris hypoplasia, focal iris atrophy, & ectropion uveae.Glaucoma develops in ~50% of affected individuals but is more common in those w/central iris changes & marked anterior iris insertionAlways bilateral, but may be distinctly asymmetric
May occur in the setting of Axenfeld-Rieger syndrome (OMIM 180500): dysmorphic features, dental anomalies, sensorineural hearing loss, cardiac malformations, endocrine & orthopedic abnormalitiesMicrocorneaUnknown 3Corneal diameter <10 mmCan be associated w/glaucoma & other ocular anomalies incl congenital cataracts, sclerocornea, & corneal plana
May be a feature of systemic syndromesCongenital hereditary endothelial dystrophy (CHED; OMIM 217700)SLC4A11ARBilateral corneal opacificationMay be difficult to distinguish from microcornea, but corneal diameter & IOP are | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1135/ | vMOr8p4 | Primary Congenital Glaucoma | C1533041 | 17 | primary congenital glaucoma. malformations, endocrine & orthopedic abnormalitiesMicrocorneaUnknown 3Corneal diameter <10 mmCan be associated w/glaucoma & other ocular anomalies incl congenital cataracts, sclerocornea, & corneal plana
May be a feature of systemic syndromesCongenital hereditary endothelial dystrophy (CHED; OMIM 217700)SLC4A11ARBilateral corneal opacificationMay be difficult to distinguish from microcornea, but corneal diameter & IOP are usually normal in CHEDThe primary defect in the corneal endothelium leads to corneal edema & opacification.CHED & CG are known to coexist; exact incidence unknown 4
Sensorineural hearing lossLowe syndromeOCRLXLDense congenital cataracts are found in all affected boys, infantile glaucoma in ~50%All boys have impaired vision; corrected acuity rarely >20/100Almost all affected males have some ID
Congenital hypotonia, delayed development, proximal renal | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1135/ | vMOr8p4 | Primary Congenital Glaucoma | C1533041 | 17 | primary congenital glaucoma. diameter & IOP are usually normal in CHEDThe primary defect in the corneal endothelium leads to corneal edema & opacification.CHED & CG are known to coexist; exact incidence unknown 4
Sensorineural hearing lossLowe syndromeOCRLXLDense congenital cataracts are found in all affected boys, infantile glaucoma in ~50%All boys have impaired vision; corrected acuity rarely >20/100Almost all affected males have some ID
Congenital hypotonia, delayed development, proximal renal tubular dysfunction (renal Fanconi type), progressive chronic renal failure and ESRD after age 10-20 yrsNeurofibromatosis type 1NF1ADIris Lisch nodulesCG rarely observed
Multiple café au lait spots, axillary & inguinal freckling, cutaneous neurofibromas, learning disabilities in ≥50% of individualsNance-Horan syndrome (OMIM 302350)NHSXLCataract and microcorneaSkeletal featuresSt | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1135/ | vMOr8p4 | Primary Congenital Glaucoma | C1533041 | 17 | primary congenital glaucoma. , delayed development, proximal renal tubular dysfunction (renal Fanconi type), progressive chronic renal failure and ESRD after age 10-20 yrsNeurofibromatosis type 1NF1ADIris Lisch nodulesCG rarely observed
Multiple café au lait spots, axillary & inguinal freckling, cutaneous neurofibromas, learning disabilities in ≥50% of individualsNance-Horan syndrome (OMIM 302350)NHSXLCataract and microcorneaSkeletal featuresSturge-Weber syndrome (OMIM 185300)GNAQSee footnote 5CG w/associated angle anomalies in ≤60% of affected individualsNevus flammeus of the face, angioma of the meningesAD = autosomal dominant; AR = autosomal recessive; CG = congenital glaucoma; ESRD = end-stage renal disease; ID = intellectual disability; MOI = mode of inheritance; WAGR = Wilms tumor-aniridia | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1135/ | vMOr8p4 | Primary Congenital Glaucoma | C1533041 | 17 | primary congenital glaucoma. microcorneaSkeletal featuresSturge-Weber syndrome (OMIM 185300)GNAQSee footnote 5CG w/associated angle anomalies in ≤60% of affected individualsNevus flammeus of the face, angioma of the meningesAD = autosomal dominant; AR = autosomal recessive; CG = congenital glaucoma; ESRD = end-stage renal disease; ID = intellectual disability; MOI = mode of inheritance; WAGR = Wilms tumor-aniridia-genital anomalies-retardation; XL = X-linked1. Pathogenic variants or deletions in PAX6 or its control elements are associated with isolated aniridia. Contiguous gene deletions including PAX6 and WT1 are associated with aniridia and the risk of one or more additional manifestations of WAGR.2. Anterior segment dysgenesis syndromes are a heterogeneous group of disorders that are usually inherited in an autosomal dominant manner with reduced penetrance.3. Huang et al 4. Ram | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1135/ | vMOr8p4 | Primary Congenital Glaucoma | C1533041 | 17 | primary congenital glaucoma. Wilms tumor-aniridia-genital anomalies-retardation; XL = X-linked1. Pathogenic variants or deletions in PAX6 or its control elements are associated with isolated aniridia. Contiguous gene deletions including PAX6 and WT1 are associated with aniridia and the risk of one or more additional manifestations of WAGR.2. Anterior segment dysgenesis syndromes are a heterogeneous group of disorders that are usually inherited in an autosomal dominant manner with reduced penetrance.3. Huang et al 4. Ramamurthy et al 5. Somatic mosaic pathogenic variants in GNAQ have been reported in individuals with Sturge-Weber syndrome.ManagementEvaluations Following Initial DiagnosisTo establish the extent of disease and needs in an individual diagnosed with primary congenital glaucoma (PCG), examination under anesthesia or sedation is warranted to make a complete assessment of both eyes. The examination includes the following:Measurement of intraocular pressure (IOP) within the first few minutes of anesthesiaMeasurement of | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1135/ | vMOr8p4 | Primary Congenital Glaucoma | C1533041 | 17 | primary congenital glaucoma. ang et al 4. Ramamurthy et al 5. Somatic mosaic pathogenic variants in GNAQ have been reported in individuals with Sturge-Weber syndrome.ManagementEvaluations Following Initial DiagnosisTo establish the extent of disease and needs in an individual diagnosed with primary congenital glaucoma (PCG), examination under anesthesia or sedation is warranted to make a complete assessment of both eyes. The examination includes the following:Measurement of intraocular pressure (IOP) within the first few minutes of anesthesiaMeasurement of corneal diameterExamination of the anterior segmentDirect gonioscopy to rule out secondary glaucomaDilated fundus examination to evaluate for optic nerve damageIf the cornea is opaque, ultrasound biomicroscopy or optical coherence tomography to aid in evaluating the anterior segment structuresMeasurement of axial lengthIf the child is examined under anesthesia, consent may be obtained to perform the appropriate surgical procedure after evaluation under anesthesia.Consultation with a clinical geneticist and/or genetic counselor is recommended. | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1135/ | vMOr8p4 | Primary Congenital Glaucoma | C1533041 | 17 | primary congenital glaucoma. minutes of anesthesiaMeasurement of corneal diameterExamination of the anterior segmentDirect gonioscopy to rule out secondary glaucomaDilated fundus examination to evaluate for optic nerve damageIf the cornea is opaque, ultrasound biomicroscopy or optical coherence tomography to aid in evaluating the anterior segment structuresMeasurement of axial lengthIf the child is examined under anesthesia, consent may be obtained to perform the appropriate surgical procedure after evaluation under anesthesia.Consultation with a clinical geneticist and/or genetic counselor is recommended.Treatment of ManifestationsThe primary goal of treatment is to decrease IOP to prevent vision-threatening complications including corneal opacification and glaucomatous optic atrophy. Early treatment to control IOP will reverse some of these complications in children. A Cochcrane review analyzed the literature that addressed the surgical management of congenital glaucoma but could not draw any conclusions from the analysis .Surgical treatment. The following approach is based on the work of deLuise & Anderson , Ho & Walton , | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1135/ | vMOr8p4 | Primary Congenital Glaucoma | C1533041 | 17 | primary congenital glaucoma. genetic counselor is recommended.Treatment of ManifestationsThe primary goal of treatment is to decrease IOP to prevent vision-threatening complications including corneal opacification and glaucomatous optic atrophy. Early treatment to control IOP will reverse some of these complications in children. A Cochcrane review analyzed the literature that addressed the surgical management of congenital glaucoma but could not draw any conclusions from the analysis .Surgical treatment. The following approach is based on the work of deLuise & Anderson , Ho & Walton , Bowman et al , Sharaawy & Bhartiya , and Al-Obeidan et al .PCG is almost always managed surgically. The primary goal of surgery is to eliminate the resistance to aqueous outflow caused by the structural abnormalities in the anterior chamber angle. This goal may be accomplished through an internal approach (goniotomy) or an external approach (trabeculotomy or trabeculectomy).In goniotomy, | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1135/ | vMOr8p4 | Primary Congenital Glaucoma | C1533041 | 17 | primary congenital glaucoma. & Walton , Bowman et al , Sharaawy & Bhartiya , and Al-Obeidan et al .PCG is almost always managed surgically. The primary goal of surgery is to eliminate the resistance to aqueous outflow caused by the structural abnormalities in the anterior chamber angle. This goal may be accomplished through an internal approach (goniotomy) or an external approach (trabeculotomy or trabeculectomy).In goniotomy, the surgeon visualizes the anterior chamber structures through a special lens (goniolens) to create openings in the trabecular meshwork. The goal of the procedure is to eliminate any resistance imposed by the abnormal trabecular meshwork. A clear cornea is necessary for direct visualization of the anterior chamber structures during this procedure.In trabeculotomy, the trabecular meshwork is incised by cannulating Schlemm's canal with a metal probe or suture via an external opening | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1135/ | vMOr8p4 | Primary Congenital Glaucoma | C1533041 | 17 | primary congenital glaucoma. In goniotomy, the surgeon visualizes the anterior chamber structures through a special lens (goniolens) to create openings in the trabecular meshwork. The goal of the procedure is to eliminate any resistance imposed by the abnormal trabecular meshwork. A clear cornea is necessary for direct visualization of the anterior chamber structures during this procedure.In trabeculotomy, the trabecular meshwork is incised by cannulating Schlemm's canal with a metal probe or suture via an external opening in the sclera.In trabeculectomy, a section of trabecular meshwork and Schlemm's canal is removed under a partial thickness sclera flap to create a wound fistula .In deep sclerectomy the dissection of a deep scleral flap, deroofing of Schlemm's canal, and preserving the structural integrity of the trabecular meshwork results in improved aqueous outflow outside the anterior chamber.Note: In contrast to goniotomy, deep sclerectomy | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1135/ | vMOr8p4 | Primary Congenital Glaucoma | C1533041 | 17 | primary congenital glaucoma. or suture via an external opening in the sclera.In trabeculectomy, a section of trabecular meshwork and Schlemm's canal is removed under a partial thickness sclera flap to create a wound fistula .In deep sclerectomy the dissection of a deep scleral flap, deroofing of Schlemm's canal, and preserving the structural integrity of the trabecular meshwork results in improved aqueous outflow outside the anterior chamber.Note: In contrast to goniotomy, deep sclerectomy, trabeculotomy, and trabeculectomy can be performed in individuals with advanced glaucoma and cloudy corneas.Glaucoma drainage implants or cyclodestruction may be used to control IOP when initial surgical procedures have failed.More than one surgical intervention may be necessary to control IOP; thus, significant morbidity is associated with both PCG and the currently available surgical treatment options. Individuals with milder forms of disease who present later in childhood often do well with a single surgical procedure and have | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1135/ | vMOr8p4 | Primary Congenital Glaucoma | C1533041 | 17 | primary congenital glaucoma. tomy, deep sclerectomy, trabeculotomy, and trabeculectomy can be performed in individuals with advanced glaucoma and cloudy corneas.Glaucoma drainage implants or cyclodestruction may be used to control IOP when initial surgical procedures have failed.More than one surgical intervention may be necessary to control IOP; thus, significant morbidity is associated with both PCG and the currently available surgical treatment options. Individuals with milder forms of disease who present later in childhood often do well with a single surgical procedure and have an excellent visual prognosis later in life.Clarity of the cornea and other ocular media, control of the ocular dimensions (corneal diameters and axial lengths), and optic nerve damage are important indicators of the course of the disease following surgery. Reported success rates for each (initial) procedure are approximately 80%. Infants with elevated IOP and cloudy corneas at birth have the poorest prognosis. The most favorable outcome is seen in infants in whom surgery is performed between the second and eighth | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1135/ | vMOr8p4 | Primary Congenital Glaucoma | C1533041 | 17 | primary congenital glaucoma. a single surgical procedure and have an excellent visual prognosis later in life.Clarity of the cornea and other ocular media, control of the ocular dimensions (corneal diameters and axial lengths), and optic nerve damage are important indicators of the course of the disease following surgery. Reported success rates for each (initial) procedure are approximately 80%. Infants with elevated IOP and cloudy corneas at birth have the poorest prognosis. The most favorable outcome is seen in infants in whom surgery is performed between the second and eighth month of life. With increasing age, surgery is less effective in preserving vision.Medications. Beta-blockers (e.g., timolol), parasympathomimetics (e.g., pilocarpine), sympathomimetics (e.g., adrenergic agonists and alpha-2 adrenergic receptor agonists), carbonic anhydrase inhibitors, and prostaglandin agonists have all been used. These medications, particularly the alpha-2 adrenergic receptor agonists, may have severe side effects and must | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1135/ | vMOr8p4 | Primary Congenital Glaucoma | C1533041 | 17 | primary congenital glaucoma. performed between the second and eighth month of life. With increasing age, surgery is less effective in preserving vision.Medications. Beta-blockers (e.g., timolol), parasympathomimetics (e.g., pilocarpine), sympathomimetics (e.g., adrenergic agonists and alpha-2 adrenergic receptor agonists), carbonic anhydrase inhibitors, and prostaglandin agonists have all been used. These medications, particularly the alpha-2 adrenergic receptor agonists, may have severe side effects and must be used with caution in infants and children .Surgery should not be delayed in an attempt to achieve medical control of IOP.Medication may be used preoperatively to lower the IOP to prevent optic nerve damage, to reduce the risk of sudden decompression of the globe, and to clear the cornea for better visualization during examination and surgery.Postoperatively, medication may help control IOP until the success of the surgical procedure is established.Medical therapy is also used when surgery may be life threatening or has led | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1135/ | vMOr8p4 | Primary Congenital Glaucoma | C1533041 | 17 | primary congenital glaucoma. have severe side effects and must be used with caution in infants and children .Surgery should not be delayed in an attempt to achieve medical control of IOP.Medication may be used preoperatively to lower the IOP to prevent optic nerve damage, to reduce the risk of sudden decompression of the globe, and to clear the cornea for better visualization during examination and surgery.Postoperatively, medication may help control IOP until the success of the surgical procedure is established.Medical therapy is also used when surgery may be life threatening or has led to incomplete control of the glaucoma .Treatment of refractive errors. Amblyopia from uncorrected refractive errors often associated with PCG must be treated to obtain optimal visual function.Prevention of Secondary ComplicationsMedications such as Phospholine Iodide® (echothiophate) need to be discontinued before surgery, especially if succinylcholine is used because of the danger of prolonged apnea.SurveillanceLifelong monitoring is necessary to ensure control of IOP to preserve remaining vision and to prevent further loss of vision | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1135/ | vMOr8p4 | Primary Congenital Glaucoma | C1533041 | 17 | primary congenital glaucoma. be life threatening or has led to incomplete control of the glaucoma .Treatment of refractive errors. Amblyopia from uncorrected refractive errors often associated with PCG must be treated to obtain optimal visual function.Prevention of Secondary ComplicationsMedications such as Phospholine Iodide® (echothiophate) need to be discontinued before surgery, especially if succinylcholine is used because of the danger of prolonged apnea.SurveillanceLifelong monitoring is necessary to ensure control of IOP to preserve remaining vision and to prevent further loss of vision; the intervals at which monitoring needs to be performed vary depending on the severity of disease and control of IOP.Once IOP is controlled and the child is visually rehabilitated, follow up is typically every three months to keep IOP at the "target" level, which depends on the severity of the glaucomatous optic nerve damage and the age of the individual. Standard clinical follow-up tests include optic nerve photography and visual field testing. The complete ophthalmic evaluation often requires examination under anesthesia or | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1135/ | vMOr8p4 | Primary Congenital Glaucoma | C1533041 | 17 | primary congenital glaucoma. to prevent further loss of vision; the intervals at which monitoring needs to be performed vary depending on the severity of disease and control of IOP.Once IOP is controlled and the child is visually rehabilitated, follow up is typically every three months to keep IOP at the "target" level, which depends on the severity of the glaucomatous optic nerve damage and the age of the individual. Standard clinical follow-up tests include optic nerve photography and visual field testing. The complete ophthalmic evaluation often requires examination under anesthesia or sedation in infants and in young and uncooperative children. This process may be challenging to the individual, the family, and the treating physician .Agents/Circumstances to AvoidAlpha-2 agonists should be avoided in children in the treatment of elevated IOP because of the risk for apnea and bradycardia.Evaluation of Relatives at RiskTesting at-risk sibs in the neonatal period may be helpful in establishing the diagnosis of PCG early and in avoiding repeated examinations under anesthesia in at- | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1135/ | vMOr8p4 | Primary Congenital Glaucoma | C1533041 | 17 | primary congenital glaucoma. often requires examination under anesthesia or sedation in infants and in young and uncooperative children. This process may be challenging to the individual, the family, and the treating physician .Agents/Circumstances to AvoidAlpha-2 agonists should be avoided in children in the treatment of elevated IOP because of the risk for apnea and bradycardia.Evaluation of Relatives at RiskTesting at-risk sibs in the neonatal period may be helpful in establishing the diagnosis of PCG early and in avoiding repeated examinations under anesthesia in at-risk young children.Molecular genetic testing alone is appropriate in sibs of affected individuals in whom the pathogenic variant(s) have been identified.If the PCG-related pathogenic variant(s) have not been identified in an affected family member (i.e., no definitive exclusion of the disease is possible by molecular genetic testing), screening including IOP measurements under anesthesia/sedation may be necessary.Note: The literature is unclear as to timing of the onset of glaucoma | [
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] |
gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1135/ | vMOr8p4 | Primary Congenital Glaucoma | C1533041 | 17 | primary congenital glaucoma. examinations under anesthesia in at-risk young children.Molecular genetic testing alone is appropriate in sibs of affected individuals in whom the pathogenic variant(s) have been identified.If the PCG-related pathogenic variant(s) have not been identified in an affected family member (i.e., no definitive exclusion of the disease is possible by molecular genetic testing), screening including IOP measurements under anesthesia/sedation may be necessary.Note: The literature is unclear as to timing of the onset of glaucoma, especially in families in whom pathogenic variants have been identified. In this high-risk group, it may be appropriate to perform yearly glaucoma screening into young adulthood.See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.Therapies Under InvestigationSearch ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1135/ | vMOr8p4 | Primary Congenital Glaucoma | C1533041 | 17 | primary congenital glaucoma. timing of the onset of glaucoma, especially in families in whom pathogenic variants have been identified. In this high-risk group, it may be appropriate to perform yearly glaucoma screening into young adulthood.See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.Therapies Under InvestigationSearch ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder. | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. SummaryClinical characteristics.Primary hyperoxaluria type 1 (PH1) is caused by a deficiency of the liver peroxisomal enzyme alanine:glyoxylate-aminotransferase (AGT), which catalyzes the conversion of glyoxylate to glycine. When AGT activity is absent, glyoxylate is converted to oxalate, which forms insoluble calcium oxalate crystals that accumulate in the kidney and other organs. Individuals with PH1 are at risk for recurrent nephrolithiasis (deposition of calcium oxalate in the renal pelvis / urinary tract), nephrocalcinosis (deposition of calcium oxalate in the renal parenchyma), or end-stage renal disease (ESRD). Age at onset of symptoms ranges from infancy to the sixth decade. Approximately 10% of affected individuals present in infancy or early childhood with nephrocalcinosis, with or without nephrolithiasis, and failure to thrive related to renal failure. The majority of individuals with PH1 present in childhood or early adolescence, usually with | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. deposition of calcium oxalate in the renal pelvis / urinary tract), nephrocalcinosis (deposition of calcium oxalate in the renal parenchyma), or end-stage renal disease (ESRD). Age at onset of symptoms ranges from infancy to the sixth decade. Approximately 10% of affected individuals present in infancy or early childhood with nephrocalcinosis, with or without nephrolithiasis, and failure to thrive related to renal failure. The majority of individuals with PH1 present in childhood or early adolescence, usually with symptomatic nephrolithiasis and normal or reduced kidney function. The remainder of affected individuals present in adulthood with recurrent renal stones and a mild-to-moderate reduction in kidney function. The natural history of untreated PH1 is one of progressive decline in renal function as a result of calcium oxalate deposits in kidney tissue and complications of nephrolithiasis (e.g., obstruction and infection) with eventual progression to oxalosis (widespread tissue deposition of calcium oxalate) and | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. present in childhood or early adolescence, usually with symptomatic nephrolithiasis and normal or reduced kidney function. The remainder of affected individuals present in adulthood with recurrent renal stones and a mild-to-moderate reduction in kidney function. The natural history of untreated PH1 is one of progressive decline in renal function as a result of calcium oxalate deposits in kidney tissue and complications of nephrolithiasis (e.g., obstruction and infection) with eventual progression to oxalosis (widespread tissue deposition of calcium oxalate) and death from ESRD and/or complications of oxalosis.Diagnosis/testing.The diagnosis of PH1 is established in a proband with hyperoxaluria or hyperoxalemia by identification biallelic pathogenic variants in AGXT on molecular genetic testing. Failure to identify at least one AGXT pathogenic variant should prompt examination for other types of primary hyperoxaluria and in occasional circumstances may require consideration of liver biopsy to assay the activity of the enzyme alanine:glyoxylate | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. (widespread tissue deposition of calcium oxalate) and death from ESRD and/or complications of oxalosis.Diagnosis/testing.The diagnosis of PH1 is established in a proband with hyperoxaluria or hyperoxalemia by identification biallelic pathogenic variants in AGXT on molecular genetic testing. Failure to identify at least one AGXT pathogenic variant should prompt examination for other types of primary hyperoxaluria and in occasional circumstances may require consideration of liver biopsy to assay the activity of the enzyme alanine:glyoxylate-aminotransferase (AGT). However, given the wide availability of genetic testing, liver biopsy to obtain tissue for enzymatic activity is now rarely employed.Management.Treatment of manifestations: Reduction of calcium oxalate supersaturation in the urine to minimize stone formation; reduction of calcium oxalate supersaturation in the plasma in individuals with ESRD to minimize systemic deposition of calcium oxalate crystals; treatment of kidney stones; reduction of oxalate biosynthesis; dialysis; organ transplantation as either liver transplantation or | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. activity of the enzyme alanine:glyoxylate-aminotransferase (AGT). However, given the wide availability of genetic testing, liver biopsy to obtain tissue for enzymatic activity is now rarely employed.Management.Treatment of manifestations: Reduction of calcium oxalate supersaturation in the urine to minimize stone formation; reduction of calcium oxalate supersaturation in the plasma in individuals with ESRD to minimize systemic deposition of calcium oxalate crystals; treatment of kidney stones; reduction of oxalate biosynthesis; dialysis; organ transplantation as either liver transplantation or combined liver/kidney transplantation.Prevention of primary manifestations: To reduce calcium oxalate supersaturation in the urine: maintenance of high fluid intake; inhibition of calcium oxalate crystal formation with potassium or sodium citrate, pyrophosphate-containing solutions. To reduce oxalate biosynthesis: pyridoxine supplements for those who are pyridoxine responsive.Surveillance: At regular intervals, obtain serum creatinine to estimate glomerular filtration rate (GFR), renal ultrasound examinations or other kidney imaging, urinalysis; and | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. dialysis; organ transplantation as either liver transplantation or combined liver/kidney transplantation.Prevention of primary manifestations: To reduce calcium oxalate supersaturation in the urine: maintenance of high fluid intake; inhibition of calcium oxalate crystal formation with potassium or sodium citrate, pyrophosphate-containing solutions. To reduce oxalate biosynthesis: pyridoxine supplements for those who are pyridoxine responsive.Surveillance: At regular intervals, obtain serum creatinine to estimate glomerular filtration rate (GFR), renal ultrasound examinations or other kidney imaging, urinalysis; and periodic fundoscopic eye examinations. Additionally:In those with reduced GFR (<60 mL/min/1.73 m2): regular measurement of plasma oxalate and more frequent monitoring of kidney function.In individuals with greatly reduced GFR (<30 mL/min/1.73 m2) or rapid deterioration in function: frequent assessment of serum creatinine and plasma oxalate. At regular intervals obtain x-ray examination of the long bones, electrocardiogram for | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. other kidney imaging, urinalysis; and periodic fundoscopic eye examinations. Additionally:In those with reduced GFR (<60 mL/min/1.73 m2): regular measurement of plasma oxalate and more frequent monitoring of kidney function.In individuals with greatly reduced GFR (<30 mL/min/1.73 m2) or rapid deterioration in function: frequent assessment of serum creatinine and plasma oxalate. At regular intervals obtain x-ray examination of the long bones, electrocardiogram for conduction abnormalities, echocardiogram for evidence of oxalate cardiomyopathy, hemoglobin, thyroid function testing, and frequent clinical evaluation for additional complications of oxalosis.Agents/circumstances to avoid: Dehydration from any cause can lead to irreversible kidney failure and should be strictly avoided. Individuals with PH1 should avoid intake of vitamin C that exceeds the recommended daily allowance, loop diuretics, high doses of nonsteroidal anti-inflammatory medications or other medications that can compromise kidney function; and large intake of | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. ray examination of the long bones, electrocardiogram for conduction abnormalities, echocardiogram for evidence of oxalate cardiomyopathy, hemoglobin, thyroid function testing, and frequent clinical evaluation for additional complications of oxalosis.Agents/circumstances to avoid: Dehydration from any cause can lead to irreversible kidney failure and should be strictly avoided. Individuals with PH1 should avoid intake of vitamin C that exceeds the recommended daily allowance, loop diuretics, high doses of nonsteroidal anti-inflammatory medications or other medications that can compromise kidney function; and large intake of foods high in oxalate (e.g., chocolate, rhubarb, starfruit).Evaluation of relatives at risk: Early diagnosis of at-risk relatives enables early institution of treatment and preventive measures.Genetic counseling.PH1 is inherited in an autosomal recessive manner. At conception, each sib of a proband with PH1 has a 25% risk of being affected, a 50% risk of being an asymptomatic carrier, and a | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. can compromise kidney function; and large intake of foods high in oxalate (e.g., chocolate, rhubarb, starfruit).Evaluation of relatives at risk: Early diagnosis of at-risk relatives enables early institution of treatment and preventive measures.Genetic counseling.PH1 is inherited in an autosomal recessive manner. At conception, each sib of a proband with PH1 has a 25% risk of being affected, a 50% risk of being an asymptomatic carrier, and a 25% risk of being unaffected and not a carrier. Carrier testing for at-risk relatives and prenatal diagnosis for pregnancies at increased risk are possible if both pathogenic variants have been identified in a family. Assay of AGT enzymatic activity prenatally is not generally offered because it requires a fetal liver biopsy.DiagnosisSuggestive FindingsPrimary hyperoxaluria type 1 (PH1) should be suspected in a proband with any of the following clinical, radiographic, and | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. risk of being an asymptomatic carrier, and a 25% risk of being unaffected and not a carrier. Carrier testing for at-risk relatives and prenatal diagnosis for pregnancies at increased risk are possible if both pathogenic variants have been identified in a family. Assay of AGT enzymatic activity prenatally is not generally offered because it requires a fetal liver biopsy.DiagnosisSuggestive FindingsPrimary hyperoxaluria type 1 (PH1) should be suspected in a proband with any of the following clinical, radiographic, and/or laboratory features.Clinical and radiographic featuresRecurrent nephrolithiasis. Renal ultrasound examination often reveals multiple bilateral radiopaque calculi (computed tomography and kidney ureter bladder x-ray may demonstrate similar findings).Nephrocalcinosis. In older children or adults, the strongest echoes are from the corticomedullary regions, whereas in infants the pattern is more likely to be that of diffuse nephrocalcinosis with few if any observable discrete stones.A child with | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. any of the following clinical, radiographic, and/or laboratory features.Clinical and radiographic featuresRecurrent nephrolithiasis. Renal ultrasound examination often reveals multiple bilateral radiopaque calculi (computed tomography and kidney ureter bladder x-ray may demonstrate similar findings).Nephrocalcinosis. In older children or adults, the strongest echoes are from the corticomedullary regions, whereas in infants the pattern is more likely to be that of diffuse nephrocalcinosis with few if any observable discrete stones.A child with a first kidney stone A child younger than age 12 months with failure to thrive and impaired kidney functionReduced kidney function or end-stage renal disease at any age with a history of renal stones or nephrocalcinosis Stone composition of pure calcium oxalate monohydrate (whewellite)Oxalate crystals identified in any biologic fluid or tissue Laboratory findingsElevated urinary oxalate excretion persistently >0.7 mmol/1.73 m2/day or above | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. if any observable discrete stones.A child with a first kidney stone A child younger than age 12 months with failure to thrive and impaired kidney functionReduced kidney function or end-stage renal disease at any age with a history of renal stones or nephrocalcinosis Stone composition of pure calcium oxalate monohydrate (whewellite)Oxalate crystals identified in any biologic fluid or tissue Laboratory findingsElevated urinary oxalate excretion persistently >0.7 mmol/1.73 m2/day or above the age-related reference range(s) (see Table 1)Elevated urinary glycolic acid (glycolate) concentration; occurs in approximately 75% of individuals with PH1 (see Table 1).Elevated plasma oxalate concentration. Individuals with PH1 and well-preserved GFR typically have mildly elevated values. Substantially elevated values are the rule when GFR is <30 mL/min/1.73 m2 (CKD stages 4 and 5). Plasma | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. /1.73 m2/day or above the age-related reference range(s) (see Table 1)Elevated urinary glycolic acid (glycolate) concentration; occurs in approximately 75% of individuals with PH1 (see Table 1).Elevated plasma oxalate concentration. Individuals with PH1 and well-preserved GFR typically have mildly elevated values. Substantially elevated values are the rule when GFR is <30 mL/min/1.73 m2 (CKD stages 4 and 5). Plasma oxalate concentrations >50 µmol/L are very suggestive of PH1 .Table 1. Normal Values for Urinary Oxalate, Glycolate, and L-Glycerate Excretion in 24-Hour Urine and Spot (Random) Urine SamplesView in own windowParameterAgeNormal Values 1Urinary oxalate excretion 2All agesIn 24-hoururinesamples<0.50 mmol (<45 mg)/1.73 m2/ | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. (CKD stages 4 and 5). Plasma oxalate concentrations >50 µmol/L are very suggestive of PH1 .Table 1. Normal Values for Urinary Oxalate, Glycolate, and L-Glycerate Excretion in 24-Hour Urine and Spot (Random) Urine SamplesView in own windowParameterAgeNormal Values 1Urinary oxalate excretion 2All agesIn 24-hoururinesamples<0.50 mmol (<45 mg)/1.73 m2/dayUrinary glycolate excretion<0.50 mmol (<45 mg)/1.73 m2/dayUrinary L-glycerateconcentration<5 μmol/LSpot urinary oxalate-to-creatinine molar ratio 30-6 mos 4In spoturinesamples 2<325-360 mmol/mol (<253-282 mg/g)7-24 mos 4< | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. 45 mg)/1.73 m2/dayUrinary glycolate excretion<0.50 mmol (<45 mg)/1.73 m2/dayUrinary L-glycerateconcentration<5 μmol/LSpot urinary oxalate-to-creatinine molar ratio 30-6 mos 4In spoturinesamples 2<325-360 mmol/mol (<253-282 mg/g)7-24 mos 4<132-174 mmol/mol (<103-136 mg/g)2-5 yrs<98-101 mmol/mol (<76-79 mg/g)5-14 yrs<70-82 mmol/mol (<55-64 mg/g)>16 yrs<40 mmol/mol (<32 mg/g)Spot urinary glycolate- | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. )7-24 mos 4<132-174 mmol/mol (<103-136 mg/g)2-5 yrs<98-101 mmol/mol (<76-79 mg/g)5-14 yrs<70-82 mmol/mol (<55-64 mg/g)>16 yrs<40 mmol/mol (<32 mg/g)Spot urinary glycolate-tocreatinine molar ratio0-6 mos 4<363-425 mmol/mol (<241-282 mg/g)7-24 mos 4<245-293 mmol/mol (<163-194 mg/g)2-5 yrs<191-229 mmol/mol (<127-152 mg/g)5-14 yrs<166-186 | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. mg/g)Spot urinary glycolate-tocreatinine molar ratio0-6 mos 4<363-425 mmol/mol (<241-282 mg/g)7-24 mos 4<245-293 mmol/mol (<163-194 mg/g)2-5 yrs<191-229 mmol/mol (<127-152 mg/g)5-14 yrs<166-186 mmol/mol (<110-123 mg/g)>16 yrs<99-125 mmol/mol (<66-83 mg/g)Spot urinary L-glycerate-tocreatinine molar ratio0-6 mos 414-205 mmol/mol (<13-192 mg/g)7-24 mos 414-205 mmol/mol (<13- | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. -14 yrs<166-186 mmol/mol (<110-123 mg/g)>16 yrs<99-125 mmol/mol (<66-83 mg/g)Spot urinary L-glycerate-tocreatinine molar ratio0-6 mos 414-205 mmol/mol (<13-192 mg/g)7-24 mos 414-205 mmol/mol (<13-192 mg/g)2-5 yrs14-205 mmol/mol (<13-192 mg/g)5-14 yrs23-138 mmol/mol (<22-129 mg/g)>16 yrs<138 mmol/mol (<129 mg/g)Adapted from Hoppe 1. Values are laboratory and method dependent.2. Urinary excretion of creatinine on a per- | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. mmol/mol (<13-192 mg/g)2-5 yrs14-205 mmol/mol (<13-192 mg/g)5-14 yrs23-138 mmol/mol (<22-129 mg/g)>16 yrs<138 mmol/mol (<129 mg/g)Adapted from Hoppe 1. Values are laboratory and method dependent.2. Urinary excretion of creatinine on a per-kg basis differs between males and females and does not stabilize until ages 14 to 18 years .3. To prevent alkaline conversion of ascorbate to oxalate in urine, the sample must be strongly acidified to stabilize ascorbate and minimize formation of calcium crystals .4. In children younger than age 1.5-2.0 years, interpretation of random urine oxalate/creatinine ratios is challenging due to rapid age-related changes associated with normal maturation. Normal newborns and young infants | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. . Urinary excretion of creatinine on a per-kg basis differs between males and females and does not stabilize until ages 14 to 18 years .3. To prevent alkaline conversion of ascorbate to oxalate in urine, the sample must be strongly acidified to stabilize ascorbate and minimize formation of calcium crystals .4. In children younger than age 1.5-2.0 years, interpretation of random urine oxalate/creatinine ratios is challenging due to rapid age-related changes associated with normal maturation. Normal newborns and young infants/children can excrete ≥3-5x the amount of oxalate excreted by adults; this amount slowly decreases into the normal adult range in the older child .Establishing the DiagnosisA guideline for diagnosis has been developed ; see Figure 1 for algorithm. The algorithm also assists the clinician in differentiating between PH types 1, 2, and 3.Figure 1. Algorithm for diagnostic evaluation of primary hyperoxaluria From Edvardsson et al . Published with perm | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. with normal maturation. Normal newborns and young infants/children can excrete ≥3-5x the amount of oxalate excreted by adults; this amount slowly decreases into the normal adult range in the older child .Establishing the DiagnosisA guideline for diagnosis has been developed ; see Figure 1 for algorithm. The algorithm also assists the clinician in differentiating between PH types 1, 2, and 3.Figure 1. Algorithm for diagnostic evaluation of primary hyperoxaluria From Edvardsson et al . Published with permission of SpringerNature.The diagnosis of PH1 is established in a proband with hyperoxaluria or hyperoxalemia by ONE of the following:Identification of biallelic pathogenic variants in AGXT on molecular genetic testing (see Table 2). Molecular genetic testing is indicated in all individuals as genotype information helps predict treatment responses (see Genotype-Phenotype Correlations).Identification of AGT enzyme deficiency on liver biopsy (see Liver biopsy)Molecular genetic testing approaches | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. rdsson et al . Published with permission of SpringerNature.The diagnosis of PH1 is established in a proband with hyperoxaluria or hyperoxalemia by ONE of the following:Identification of biallelic pathogenic variants in AGXT on molecular genetic testing (see Table 2). Molecular genetic testing is indicated in all individuals as genotype information helps predict treatment responses (see Genotype-Phenotype Correlations).Identification of AGT enzyme deficiency on liver biopsy (see Liver biopsy)Molecular genetic testing approaches can include single-gene testing, use of a multigene panel, and more comprehensive genomic testing:Single-gene testing. Sequence analysis of AGXT is performed first and followed by gene-targeted deletion/duplication analysis if only one or no pathogenic variant is found.Sequence analysis includes testing for the common AGXT polymorphic variant, p.Pro11Leu. Although p.Pro11Leu, referred to as the "minor allele," does not | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. (see Liver biopsy)Molecular genetic testing approaches can include single-gene testing, use of a multigene panel, and more comprehensive genomic testing:Single-gene testing. Sequence analysis of AGXT is performed first and followed by gene-targeted deletion/duplication analysis if only one or no pathogenic variant is found.Sequence analysis includes testing for the common AGXT polymorphic variant, p.Pro11Leu. Although p.Pro11Leu, referred to as the "minor allele," does not cause PH1 by itself, it is known to exacerbate the deleterious effects of other pathogenic variants in cis configuration (see Molecular Genetics).A multigene panel that includes AGXT and other genes of interest (e.g., GRHPR, HOGA1 ) is now recommended. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. as the "minor allele," does not cause PH1 by itself, it is known to exacerbate the deleterious effects of other pathogenic variants in cis configuration (see Molecular Genetics).A multigene panel that includes AGXT and other genes of interest (e.g., GRHPR, HOGA1 ) is now recommended. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview; thus, clinicians need to determine which multigene panel is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview; thus, clinicians need to determine which multigene panel is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.More comprehensive genomic testing (when available) including exome sequencing and genome sequencing may be considered. Such testing may provide or suggest a diagnosis | [
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] |
gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.More comprehensive genomic testing (when available) including exome sequencing and genome sequencing may be considered. Such testing may provide or suggest a diagnosis not previously considered (e.g., mutation of a different gene or genes that results in a similar clinical presentation For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here.Table 2. Molecular Genetic Testing Used in Primary Hyperoxaluria Type 1View in own windowGene 1MethodProportion of Probands with Pathogenic Variants 2 Detectable by MethodAGXTSequence analysis 3>97 | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. . Such testing may provide or suggest a diagnosis not previously considered (e.g., mutation of a different gene or genes that results in a similar clinical presentation For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here.Table 2. Molecular Genetic Testing Used in Primary Hyperoxaluria Type 1View in own windowGene 1MethodProportion of Probands with Pathogenic Variants 2 Detectable by MethodAGXTSequence analysis 3>97% 4Gene-targeted deletion/duplication analysis 5<3% 6Unknown 7NA1. See Table A. Genes and Databases for chromosome locus and protein.2. See Molecular Genetics for information on allelic variants detected in this gene.3. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. quence analysis 3>97% 4Gene-targeted deletion/duplication analysis 5<3% 6Unknown 7NA1. See Table A. Genes and Databases for chromosome locus and protein.2. See Molecular Genetics for information on allelic variants detected in this gene.3. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.4. Coulter-Mackie et al 5. Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.4. Coulter-Mackie et al 5. Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.6. Out of more than 170 known AGXT pathogenic variants, six large deletions have been reported .7. The phenotype in PH2 and PH3 can appear similar to PH1 (without detailed biochemical analysis), 11.3% of families with a PH-like phenotype were not found to have pathogenic variants in AGXT, GRHPR, or HOGA1 . It is not known what percentage of these individuals have | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. a gene-targeted microarray designed to detect single-exon deletions or duplications.6. Out of more than 170 known AGXT pathogenic variants, six large deletions have been reported .7. The phenotype in PH2 and PH3 can appear similar to PH1 (without detailed biochemical analysis), 11.3% of families with a PH-like phenotype were not found to have pathogenic variants in AGXT, GRHPR, or HOGA1 . It is not known what percentage of these individuals have PH1.Liver biopsy. If urinary glycerate, 4-hydroxyoxoglutarate (HOG), and dihydroxyglutarate (DHG) are normal, and no AGXT, GRHPR, or HOGA1 pathogenic variants are identified, liver biopsy can be performed to assay alanine:glyoxylate-aminotransferase (AGT), glyoxylate reductase (GR), and 4-hydroxy-2-oxoglutarate aldolase (HO | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. is not known what percentage of these individuals have PH1.Liver biopsy. If urinary glycerate, 4-hydroxyoxoglutarate (HOG), and dihydroxyglutarate (DHG) are normal, and no AGXT, GRHPR, or HOGA1 pathogenic variants are identified, liver biopsy can be performed to assay alanine:glyoxylate-aminotransferase (AGT), glyoxylate reductase (GR), and 4-hydroxy-2-oxoglutarate aldolase (HOGA) enzyme activity. Normal GR and HOGA enzyme activity will rule out PH types 2 and 3 as the cause of the hyperoxaluria (see Primary Hyperoxaluria Type 2 and Primary Hyperoxaluria Type 3). Individuals with clinical features suggestive of PH who have AGT enzyme deficiency on liver biopsy and do not have identified AGXT pathogenic variants have a presumed diagnosis of PH1. Individuals who do not have identifed pathogenic variants in AGXT, | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. 2-oxoglutarate aldolase (HOGA) enzyme activity. Normal GR and HOGA enzyme activity will rule out PH types 2 and 3 as the cause of the hyperoxaluria (see Primary Hyperoxaluria Type 2 and Primary Hyperoxaluria Type 3). Individuals with clinical features suggestive of PH who have AGT enzyme deficiency on liver biopsy and do not have identified AGXT pathogenic variants have a presumed diagnosis of PH1. Individuals who do not have identifed pathogenic variants in AGXT, GRHPR, or HOGA1 accounted for 11.3% of individuals with hyperoxaluria tested in one recent series .Clinical CharacteristicsClinical DescriptionIn primary hyperoxaluria type 1 (PH1), high concentrations of oxalate in the urine combine with calcium resulting in calcium oxalate crystal formation. Crystal deposition leads to nephrolithiasis in the urinary tract, renal tubular damage, and nephrocalcinosis when the crystals deposit in the renal parenchyma. Progressive kidney | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. have identifed pathogenic variants in AGXT, GRHPR, or HOGA1 accounted for 11.3% of individuals with hyperoxaluria tested in one recent series .Clinical CharacteristicsClinical DescriptionIn primary hyperoxaluria type 1 (PH1), high concentrations of oxalate in the urine combine with calcium resulting in calcium oxalate crystal formation. Crystal deposition leads to nephrolithiasis in the urinary tract, renal tubular damage, and nephrocalcinosis when the crystals deposit in the renal parenchyma. Progressive kidney damage and ultimately renal failure ensue. As declining glomerular filtration rate (GFR) limits excretion of the excess oxalate, plasma levels rise rapidly. Supersaturation of calcium oxalate in plasma then results in calcium oxalate deposition in many organs and tissues (oxalosis) with systemic manifestations.The clinical presentation of PH1 is variable. Age at onset of symptoms ranges from early infancy to the sixth decade (median age: 4-6 years) . The majority of individuals present | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. crystals deposit in the renal parenchyma. Progressive kidney damage and ultimately renal failure ensue. As declining glomerular filtration rate (GFR) limits excretion of the excess oxalate, plasma levels rise rapidly. Supersaturation of calcium oxalate in plasma then results in calcium oxalate deposition in many organs and tissues (oxalosis) with systemic manifestations.The clinical presentation of PH1 is variable. Age at onset of symptoms ranges from early infancy to the sixth decade (median age: 4-6 years) . The majority of individuals present with symptoms related to nephrolithiasis. Some present with a severe, very early-onset form of PH1 in the first year of life characterized by failure to thrive and end-stage renal disease (ESRD). At the other end of the spectrum of clinical severity seen in PH1, some individuals remain free of symptoms or minimally symptomatic into the sixth decade of life .Renal manifestations. The renal manifestations of PH1 can be quite variable, with individuals | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. 6 years) . The majority of individuals present with symptoms related to nephrolithiasis. Some present with a severe, very early-onset form of PH1 in the first year of life characterized by failure to thrive and end-stage renal disease (ESRD). At the other end of the spectrum of clinical severity seen in PH1, some individuals remain free of symptoms or minimally symptomatic into the sixth decade of life .Renal manifestations. The renal manifestations of PH1 can be quite variable, with individuals generally falling into one of five groups:Early nephrocalcinosis and renal failure in infancy or early childhood (accounts for ~10% of individuals with PH1 in Europe and North America)Recurrent nephrolithiasis and progressive renal failure with diagnosis in childhood, adolescence, or early to mid-adulthood (accounts for majority of affected individuals)Diagnosis after ESRD that is first recognized due to oxalate deposits on renal biopsy, recurrent oxalate nephropathy in a renal allograft following renal transplantation | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. PH1 can be quite variable, with individuals generally falling into one of five groups:Early nephrocalcinosis and renal failure in infancy or early childhood (accounts for ~10% of individuals with PH1 in Europe and North America)Recurrent nephrolithiasis and progressive renal failure with diagnosis in childhood, adolescence, or early to mid-adulthood (accounts for majority of affected individuals)Diagnosis after ESRD that is first recognized due to oxalate deposits on renal biopsy, recurrent oxalate nephropathy in a renal allograft following renal transplantation or due to systemic oxalosis developing during chronic dialysis. (~10% of affected individuals)Late-onset form with occasional stones diagnosed in adulthood (<10%)Diagnosis in a presymptomatic individual because of a positive family history (<10%)In individuals with severe, early-onset (infantile) disease, the presenting signs and symptoms include nephrocalcinosis with or without nephrolithiasis and failure to thrive related to | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. oxalate nephropathy in a renal allograft following renal transplantation or due to systemic oxalosis developing during chronic dialysis. (~10% of affected individuals)Late-onset form with occasional stones diagnosed in adulthood (<10%)Diagnosis in a presymptomatic individual because of a positive family history (<10%)In individuals with severe, early-onset (infantile) disease, the presenting signs and symptoms include nephrocalcinosis with or without nephrolithiasis and failure to thrive related to renal failure. ESRD can appear as early as age four to six months. In most series in Europe and the US severe infantile oxalosis with kidney failure accounts for 10% or less of individuals with PH1 . However, the proportion appears higher in some areas of the world . One limitation of current understanding of the natural history of PH1 is that a large majority of individuals and nearly all large reported series are from Europe and North America.Presenting symptoms from early | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. olithiasis and failure to thrive related to renal failure. ESRD can appear as early as age four to six months. In most series in Europe and the US severe infantile oxalosis with kidney failure accounts for 10% or less of individuals with PH1 . However, the proportion appears higher in some areas of the world . One limitation of current understanding of the natural history of PH1 is that a large majority of individuals and nearly all large reported series are from Europe and North America.Presenting symptoms from early childhood through adolescence are most often related to kidney stone disease including hematuria, dysuria, pain, urinary tract infection, or stone passage . Nephrocalcinosis is common . Initial symptoms occur in most individuals before age ten years, and in 85%-90% by age 20 years . Median age of onset of symptoms was 3.9 to 5.2 years .The remainder of affected individuals present in adulthood with recurrent renal stones . Many adults report a history of | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. Europe and North America.Presenting symptoms from early childhood through adolescence are most often related to kidney stone disease including hematuria, dysuria, pain, urinary tract infection, or stone passage . Nephrocalcinosis is common . Initial symptoms occur in most individuals before age ten years, and in 85%-90% by age 20 years . Median age of onset of symptoms was 3.9 to 5.2 years .The remainder of affected individuals present in adulthood with recurrent renal stones . Many adults report a history of unrecognized symptoms and missed or delayed diagnosis. A mild-to-moderate reduction in kidney function is common, though the rate of decline is highly variable. Some individuals, mainly adults, may present with acute renal failure secondary to bilateral renal obstruction caused by calcium oxalate stones or due to other illnesses that compromise fluid intake and thus urine volume. Acute renal failure has also been reported following stone removal procedures . Twenty percent to 50% of individuals with adult-onset PH1 | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. renal stones . Many adults report a history of unrecognized symptoms and missed or delayed diagnosis. A mild-to-moderate reduction in kidney function is common, though the rate of decline is highly variable. Some individuals, mainly adults, may present with acute renal failure secondary to bilateral renal obstruction caused by calcium oxalate stones or due to other illnesses that compromise fluid intake and thus urine volume. Acute renal failure has also been reported following stone removal procedures . Twenty percent to 50% of individuals with adult-onset PH1 were diagnosed when they presented in the late stages of chronic kidney disease (CKD) or ESRD . A higher prevalence of ESRD without a prior history of renal stones was observed in a national study of individuals with PH1 from the Netherlands . The proportion of individuals with ESRD at the time of diagnosis is higher in adults than in children . The median age of individuals with PH1 who reach ESRD prior to diagnosis is 25 years (range: early childhood to late middle age | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. % of individuals with adult-onset PH1 were diagnosed when they presented in the late stages of chronic kidney disease (CKD) or ESRD . A higher prevalence of ESRD without a prior history of renal stones was observed in a national study of individuals with PH1 from the Netherlands . The proportion of individuals with ESRD at the time of diagnosis is higher in adults than in children . The median age of individuals with PH1 who reach ESRD prior to diagnosis is 25 years (range: early childhood to late middle age) . In approximately 10% of individuals the diagnosis of PH1 is made only following recurrence in a renal transplant when calcium oxalate crystals are found on allograft biopsy performed for early nonfunction of the transplanted kidney or a subsequent increase in serum creatinine .Progression to renal failure has been shown to correlate with urine oxalate excretion rate and with nephrocalcinosis . AGXT pathogenic variant p.Gly170Arg is associated with a milder phenotype, with lower urine oxalate excretion, responsiveness | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. (range: early childhood to late middle age) . In approximately 10% of individuals the diagnosis of PH1 is made only following recurrence in a renal transplant when calcium oxalate crystals are found on allograft biopsy performed for early nonfunction of the transplanted kidney or a subsequent increase in serum creatinine .Progression to renal failure has been shown to correlate with urine oxalate excretion rate and with nephrocalcinosis . AGXT pathogenic variant p.Gly170Arg is associated with a milder phenotype, with lower urine oxalate excretion, responsiveness to pyridoxine treatment, and later onset of ESRD . Later onset of ESRD has also been reported with the mistargeting pathogenic variant p.Phe152Ile ; other mistargeting pathogenic variants do not appear to delay the onset of ESRD . The natural history of untreated PH1 is one of progressive decline in renal function as a result of calcium oxalate deposits in kidney tissue and complications of nephrolithiasis such as obstruction and infection. A recent study found renal survival in | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. phenotype, with lower urine oxalate excretion, responsiveness to pyridoxine treatment, and later onset of ESRD . Later onset of ESRD has also been reported with the mistargeting pathogenic variant p.Phe152Ile ; other mistargeting pathogenic variants do not appear to delay the onset of ESRD . The natural history of untreated PH1 is one of progressive decline in renal function as a result of calcium oxalate deposits in kidney tissue and complications of nephrolithiasis such as obstruction and infection. A recent study found renal survival in individuals with PH1 to be 76%, 43%, and 12% at ages 20, 40, and 60 years, respectively . Another study noted renal survival of 59%, 41%, and 10% at ages 20, 30, and 50 years, respectively . In the absence of treatment there is eventual progression to oxalosis and death from ESRD and/or complications of oxalosis .Among 54 children and adolescents with PH1 who developed ESRD from 2000 | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. infection. A recent study found renal survival in individuals with PH1 to be 76%, 43%, and 12% at ages 20, 40, and 60 years, respectively . Another study noted renal survival of 59%, 41%, and 10% at ages 20, 30, and 50 years, respectively . In the absence of treatment there is eventual progression to oxalosis and death from ESRD and/or complications of oxalosis .Among 54 children and adolescents with PH1 who developed ESRD from 2000 through 2009, five-year survival was 83% following initiation of renal replacement therapy. Results showed improvement compared with renal replacement therapy prior to 2000, particularly in children younger than age two years. However, outcomes were less favorable in children with PH1 who required renal replacement compared to children with other renal diseases . In a series of six individuals with PH1 with infantile oxalosis, excellent outcomes were reported following combined kidney/liver transplantation at a mean age of 14 | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. adolescents with PH1 who developed ESRD from 2000 through 2009, five-year survival was 83% following initiation of renal replacement therapy. Results showed improvement compared with renal replacement therapy prior to 2000, particularly in children younger than age two years. However, outcomes were less favorable in children with PH1 who required renal replacement compared to children with other renal diseases . In a series of six individuals with PH1 with infantile oxalosis, excellent outcomes were reported following combined kidney/liver transplantation at a mean age of 14.8 months following a mean of 11.8 months of dialysis .Oxalosis. When the GFR is <30 mL/min/1.73 m2, the daily production of oxalate outstrips renal oxalate clearance, resulting in acceleration of the rise in plasma oxalate concentration associated with declining GFR, and further loss in residual renal function. Supersaturation in plasma leads to deposition of calcium oxalate crystals in multiple body tissues (oxalosis), including the | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. /liver transplantation at a mean age of 14.8 months following a mean of 11.8 months of dialysis .Oxalosis. When the GFR is <30 mL/min/1.73 m2, the daily production of oxalate outstrips renal oxalate clearance, resulting in acceleration of the rise in plasma oxalate concentration associated with declining GFR, and further loss in residual renal function. Supersaturation in plasma leads to deposition of calcium oxalate crystals in multiple body tissues (oxalosis), including the kidneys, retina, myocardium, blood vessels, bone, bone marrow, and subcutaneous tissue . Peripheral nerves, synovia, and other tissues may also be involved . Clinical manifestations may include visual disturbance, cardiac conduction disturbances such as heart block, and cardiomyopathy. Vascular involvement can lead to ischemia, most often manifest as non-healing cutaneous ulcers. Though unusual, cerebral infarcts have been reported from calcium oxalate in cerebral vessels . Refractory hypotension can be seen in advanced oxalosis | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. body tissues (oxalosis), including the kidneys, retina, myocardium, blood vessels, bone, bone marrow, and subcutaneous tissue . Peripheral nerves, synovia, and other tissues may also be involved . Clinical manifestations may include visual disturbance, cardiac conduction disturbances such as heart block, and cardiomyopathy. Vascular involvement can lead to ischemia, most often manifest as non-healing cutaneous ulcers. Though unusual, cerebral infarcts have been reported from calcium oxalate in cerebral vessels . Refractory hypotension can be seen in advanced oxalosis. Bone is the largest repository for excess oxalate. Oxalate osteodystrophy causes bone pain and pathologic fractures. Involvement of bone marrow can result in anemia refractory to erythropoietin-stimulating agents (ESA). Dental pain due to oxalate deposition and root resorption have been described . Peripheral neuropathy can be caused by crystal deposition within nerve . Progressive oxalosis, observed over time in most individuals with PH on dialysis, eventually leads to death. Oxalosis is slowly reversible following successful | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. Refractory hypotension can be seen in advanced oxalosis. Bone is the largest repository for excess oxalate. Oxalate osteodystrophy causes bone pain and pathologic fractures. Involvement of bone marrow can result in anemia refractory to erythropoietin-stimulating agents (ESA). Dental pain due to oxalate deposition and root resorption have been described . Peripheral neuropathy can be caused by crystal deposition within nerve . Progressive oxalosis, observed over time in most individuals with PH on dialysis, eventually leads to death. Oxalosis is slowly reversible following successful liver and kidney transplantation, but mobilization of the tissue deposits poses risk for a transplanted kidney.Bone mineral density measurements, as opposed to the gold standard of bone biopsy, allow for noninvasive assessment of oxalate burden , though interpretation of bone density is complicated by multiple bone changes related to ESRD.PathophysiologyThe stone type most prevalent in individuals with PH1 is calcium oxalate monohydrate or whewellite . These authors noted that stones from individuals with PH1 differ in morphologic | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. death. Oxalosis is slowly reversible following successful liver and kidney transplantation, but mobilization of the tissue deposits poses risk for a transplanted kidney.Bone mineral density measurements, as opposed to the gold standard of bone biopsy, allow for noninvasive assessment of oxalate burden , though interpretation of bone density is complicated by multiple bone changes related to ESRD.PathophysiologyThe stone type most prevalent in individuals with PH1 is calcium oxalate monohydrate or whewellite . These authors noted that stones from individuals with PH1 differ in morphologic characteristics from idiopathic calcium oxalate stone formers: they appear white or pale yellow on the surface and form a loose, unorganized section whereas idiopathic oxalate stone formers appear as a dark-brown surface with a well-organized radiating inner structure. These differences in morphology suggest a different mechanism of stone formation from idiopathic oxalate stones.Genotype-Phenotype CorrelationsPathogenic variants that result in mistargeting of alanine:glyoxylate-aminotransferase (AGT) enzyme activity | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. stones from individuals with PH1 differ in morphologic characteristics from idiopathic calcium oxalate stone formers: they appear white or pale yellow on the surface and form a loose, unorganized section whereas idiopathic oxalate stone formers appear as a dark-brown surface with a well-organized radiating inner structure. These differences in morphology suggest a different mechanism of stone formation from idiopathic oxalate stones.Genotype-Phenotype CorrelationsPathogenic variants that result in mistargeting of alanine:glyoxylate-aminotransferase (AGT) enzyme activity (see Molecular Genetics, Abnormal gene product) are the most likely to be associated with B6 (pyridoxine) responsiveness .Homozygotes for either c.508G>A (p.Gly170Arg) or c.454T>A (p.Phe152Ile) show B6 responsiveness and benefit from early treatment (see Management).Response to B6 therapy is relative to the number of copies of the p.Gly170Arg | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. ate-aminotransferase (AGT) enzyme activity (see Molecular Genetics, Abnormal gene product) are the most likely to be associated with B6 (pyridoxine) responsiveness .Homozygotes for either c.508G>A (p.Gly170Arg) or c.454T>A (p.Phe152Ile) show B6 responsiveness and benefit from early treatment (see Management).Response to B6 therapy is relative to the number of copies of the p.Gly170Arg pathogenic variant present . Compound heterozygotes for these pathogenic variants also demonstrate a reduction in urine oxalate following B6 treatment, though less than observed in homozygotes.Results of in vitro studies suggest that additional pathogenic variants may respond to B6, reinforcing the recommendation of testing all individuals for B6 responsiveness .The presence of the p.Gly170Arg pathogenic variant is associated with lower urine oxalate excretion rates even in the absence of treatment and could even predict disease severity and/or rate of progression | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. of copies of the p.Gly170Arg pathogenic variant present . Compound heterozygotes for these pathogenic variants also demonstrate a reduction in urine oxalate following B6 treatment, though less than observed in homozygotes.Results of in vitro studies suggest that additional pathogenic variants may respond to B6, reinforcing the recommendation of testing all individuals for B6 responsiveness .The presence of the p.Gly170Arg pathogenic variant is associated with lower urine oxalate excretion rates even in the absence of treatment and could even predict disease severity and/or rate of progression . A large retrospective study of individuals with PH1 suggested that the p.Gly170Arg pathogenic variant is associated with longer preservation of renal function with conservative treatment compared to other pathogenic variants .Although it may be possible to establish a relationship between the AGXT genotype and AGT enzyme activity in vitro, in most cases it is difficult to correlate enzyme activity with clinical severity .The clinical course of PH1 in affected sibs is usually similar; however, families in | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. predict disease severity and/or rate of progression . A large retrospective study of individuals with PH1 suggested that the p.Gly170Arg pathogenic variant is associated with longer preservation of renal function with conservative treatment compared to other pathogenic variants .Although it may be possible to establish a relationship between the AGXT genotype and AGT enzyme activity in vitro, in most cases it is difficult to correlate enzyme activity with clinical severity .The clinical course of PH1 in affected sibs is usually similar; however, families in which affected relatives with identical pathogenic variants had different disease manifestations have been described . Possible causes of this intrafamilial variation include differences in activity level of other enzymes important in oxalate synthesis, modifier genes, the quantity of oxalate precursors in the diet, renal oxalate handling, absorption of dietary oxalate, hydration status, infections, and urinary crystallization factors .Other than potential delay in diagnosis due to the rarity of PH1, the reason for a poorer outcome in infants with the | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. s is usually similar; however, families in which affected relatives with identical pathogenic variants had different disease manifestations have been described . Possible causes of this intrafamilial variation include differences in activity level of other enzymes important in oxalate synthesis, modifier genes, the quantity of oxalate precursors in the diet, renal oxalate handling, absorption of dietary oxalate, hydration status, infections, and urinary crystallization factors .Other than potential delay in diagnosis due to the rarity of PH1, the reason for a poorer outcome in infants with the same pathogenic variants as older individuals is not clear. Possibilities include:The low glomerular filtration rate (both absolute and corrected) in children younger than age six to 12 months, which predisposes to earlier oxalate deposition ;High oxalate excretion in infants (Table 1);Reduced number of nephrons present at birth, which may be associated with low birth weight as well as environmental and genetic factors .NomenclatureWith the identification of oxalate in human urine in the 1800s, | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. reason for a poorer outcome in infants with the same pathogenic variants as older individuals is not clear. Possibilities include:The low glomerular filtration rate (both absolute and corrected) in children younger than age six to 12 months, which predisposes to earlier oxalate deposition ;High oxalate excretion in infants (Table 1);Reduced number of nephrons present at birth, which may be associated with low birth weight as well as environmental and genetic factors .NomenclatureWith the identification of oxalate in human urine in the 1800s, hyperoxaluria fell into a category referred to as "oxalate diathesis" – a catch-all term for a wide variety of ailments.PH1 can be considered a peroxisomal disorder, as it results from deficiency of a single peroxisomal enzyme. PH1, however, is distinct from disorders of peroxisomal biogenesis (see Peroxisomal Biogenesis Disorders, Zellweger Type and Rhizomelic Chondrodysplasia Punctata Type 1) in that a normal number | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. oxalate in human urine in the 1800s, hyperoxaluria fell into a category referred to as "oxalate diathesis" – a catch-all term for a wide variety of ailments.PH1 can be considered a peroxisomal disorder, as it results from deficiency of a single peroxisomal enzyme. PH1, however, is distinct from disorders of peroxisomal biogenesis (see Peroxisomal Biogenesis Disorders, Zellweger Type and Rhizomelic Chondrodysplasia Punctata Type 1) in that a normal number of relatively normal-looking peroxisomes are observed on liver biopsy.PrevalencePH1 is estimated to account for 1%-2% of children with end-stage renal disease (ESRD) .When considering the following statistics, it is important to remember that PH1 remains underdiagnosed because of the wide variability in its clinical presentation and age of onset.Clinical estimates of prevalence of PH1, primarily from European studies, range from one to three in 1,000, | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. ata Type 1) in that a normal number of relatively normal-looking peroxisomes are observed on liver biopsy.PrevalencePH1 is estimated to account for 1%-2% of children with end-stage renal disease (ESRD) .When considering the following statistics, it is important to remember that PH1 remains underdiagnosed because of the wide variability in its clinical presentation and age of onset.Clinical estimates of prevalence of PH1, primarily from European studies, range from one to three in 1,000,000 . PH1 is estimated to occur in 1:120,000 live births in Europe . Since phenotypic heterogeneity ranges from severe disease in infancy to adults with recurrent stones, and since advanced disease is present in 20%-50% at the time of diagnosis, underdiagnosis likely occurs. Population analysis based on AGXT pathogenic variants identified in the National Heart, Lung, and Blood Institute Exome Sequencing Project suggest a PH1 prevalence of 1:149,000 in | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. from one to three in 1,000,000 . PH1 is estimated to occur in 1:120,000 live births in Europe . Since phenotypic heterogeneity ranges from severe disease in infancy to adults with recurrent stones, and since advanced disease is present in 20%-50% at the time of diagnosis, underdiagnosis likely occurs. Population analysis based on AGXT pathogenic variants identified in the National Heart, Lung, and Blood Institute Exome Sequencing Project suggest a PH1 prevalence of 1:149,000 in European Americans and 1:157,000 in African Americans .A higher frequency of PH1 has been reported in Tunisia and Kuwait , in Arabs and Druze families of Israel , and in Iran as a result of the high rate of consanguinity in these populations. No common founder variant has been identified in these populations .Differential DiagnosisPrimary hyperoxaluria type 2
(PH2) is caused by pathogenic variants in GRHPR | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. 1 prevalence of 1:149,000 in European Americans and 1:157,000 in African Americans .A higher frequency of PH1 has been reported in Tunisia and Kuwait , in Arabs and Druze families of Israel , and in Iran as a result of the high rate of consanguinity in these populations. No common founder variant has been identified in these populations .Differential DiagnosisPrimary hyperoxaluria type 2
(PH2) is caused by pathogenic variants in GRHPR, resulting in deficiency of the cytosolic enzyme glyoxylate reductase/hydroxypyruvate reductase (GRHPR), which catalyzes the reduction of glyoxylate and hydroxypyruvate to D-glycerate. While found in many tissues, GRHPR is mainly found in hepatocytes with some expression in mitochondria. In PH2, glyoxylate removal is impaired, resulting in the metabolism of glyoxylate by lactate dehydrogenase to oxalate and L-glycerate. | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. is caused by pathogenic variants in GRHPR, resulting in deficiency of the cytosolic enzyme glyoxylate reductase/hydroxypyruvate reductase (GRHPR), which catalyzes the reduction of glyoxylate and hydroxypyruvate to D-glycerate. While found in many tissues, GRHPR is mainly found in hepatocytes with some expression in mitochondria. In PH2, glyoxylate removal is impaired, resulting in the metabolism of glyoxylate by lactate dehydrogenase to oxalate and L-glycerate.The diagnosis of PH2 can be established by sequence analysis of GHPRH or assay of GRHPR enzymatic activity in liver. Inheritance is autosomal recessive.PH2 is rarer than PH1. It is associated with better preservation of kidney function than PH1 .From a small cohort of individuals with PH1 and PH2 from one center, PH1 as a group appears to differ from PH2 in the following respects:PH2 is considered a less | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. dehydrogenase to oxalate and L-glycerate.The diagnosis of PH2 can be established by sequence analysis of GHPRH or assay of GRHPR enzymatic activity in liver. Inheritance is autosomal recessive.PH2 is rarer than PH1. It is associated with better preservation of kidney function than PH1 .From a small cohort of individuals with PH1 and PH2 from one center, PH1 as a group appears to differ from PH2 in the following respects:PH2 is considered a less aggressive disease than PH1, even when onset is early.Individuals with PH1 have statistically higher urine oxalate excretions and more stone-forming activity and thus require more frequent stone removal.Individuals with PH1 have statistically lower urine osmolalities and lower urine concentration of calcium, citrate, and magnesium. (For a single individual with hyperoxaluria, the differences observed cannot reliably distinguish PH1 from PH2.)In individuals with PH1, urinary glycol | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. following respects:PH2 is considered a less aggressive disease than PH1, even when onset is early.Individuals with PH1 have statistically higher urine oxalate excretions and more stone-forming activity and thus require more frequent stone removal.Individuals with PH1 have statistically lower urine osmolalities and lower urine concentration of calcium, citrate, and magnesium. (For a single individual with hyperoxaluria, the differences observed cannot reliably distinguish PH1 from PH2.)In individuals with PH1, urinary glycolate (as well as oxalate) is often elevated, although some individuals with PH1 have normal urine glycolate.In individuals with PH2, urinary L-glycerate and oxalate are generally elevated; a single individual with PH2 and normal urine glycerate has been reported .Primary hyperoxaluria type 3
(PH3) is caused by a defect in the hepatocyte-specific mitochondrial enzyme 4-hydroxy-2-oxoglutarate aldolase (HOGA | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. )In individuals with PH1, urinary glycolate (as well as oxalate) is often elevated, although some individuals with PH1 have normal urine glycolate.In individuals with PH2, urinary L-glycerate and oxalate are generally elevated; a single individual with PH2 and normal urine glycerate has been reported .Primary hyperoxaluria type 3
(PH3) is caused by a defect in the hepatocyte-specific mitochondrial enzyme 4-hydroxy-2-oxoglutarate aldolase (HOGA), which appears to lead to excess metabolism of hydroxyproline with the forward reaction product (HOG) itself being converted to pyruvate or glyoxalate or perhaps actually inhibiting mitochondrial GRHPR (effectively causing "secondary" PH2). Pathogenic variants in HOGA1 are causative. Diagnosis is by exclusion of PH1 and PH2 with confirmation by DNA sequence analysis of HOGA1. Inheritance is autosomal recessive.Enteric hyperoxaluria. Diseases affecting the small | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. -oxoglutarate aldolase (HOGA), which appears to lead to excess metabolism of hydroxyproline with the forward reaction product (HOG) itself being converted to pyruvate or glyoxalate or perhaps actually inhibiting mitochondrial GRHPR (effectively causing "secondary" PH2). Pathogenic variants in HOGA1 are causative. Diagnosis is by exclusion of PH1 and PH2 with confirmation by DNA sequence analysis of HOGA1. Inheritance is autosomal recessive.Enteric hyperoxaluria. Diseases affecting the small bowel that result in fat malabsorption including celiac disease, Crohn's disease, pancreatitis, and short bowel syndrome can be associated with hyperoxaluria. The precipitation of enteric calcium by non-absorbed free fatty acids leads to loss of the normal inhibition in oxalate reabsorption from the gut, increasing plasma oxalate concentration by increasing paracellular and transcellular transport. Delivery of excess fatty acids and bile salts to the colon also injures the mucosa and increases oxalate absorption . By contrast | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. Enteric hyperoxaluria. Diseases affecting the small bowel that result in fat malabsorption including celiac disease, Crohn's disease, pancreatitis, and short bowel syndrome can be associated with hyperoxaluria. The precipitation of enteric calcium by non-absorbed free fatty acids leads to loss of the normal inhibition in oxalate reabsorption from the gut, increasing plasma oxalate concentration by increasing paracellular and transcellular transport. Delivery of excess fatty acids and bile salts to the colon also injures the mucosa and increases oxalate absorption . By contrast, individuals with PH1 show low-to-normal levels of oxalate absorption . Gastric bypass procedures used in the treatment of obesity have been associated with increased oxalate absorption, high levels of hyperoxaluria, increased risk of kidney stone formation, and ESRD caused by oxalate nephropathy . Urinary risk factors for stones such as hyperoxaluria occur more commonly in individuals with Roux-en-Y gastric bypass than gastric banding .Dietary hyperoxaluria. Excess intake of foods high | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. the mucosa and increases oxalate absorption . By contrast, individuals with PH1 show low-to-normal levels of oxalate absorption . Gastric bypass procedures used in the treatment of obesity have been associated with increased oxalate absorption, high levels of hyperoxaluria, increased risk of kidney stone formation, and ESRD caused by oxalate nephropathy . Urinary risk factors for stones such as hyperoxaluria occur more commonly in individuals with Roux-en-Y gastric bypass than gastric banding .Dietary hyperoxaluria. Excess intake of foods high in oxalate including chocolate, cocoa, leafy greens (especially rhubarb and spinach), black tea, nuts, peanut butter, or starfruit may lead to elevated plasma concentration of oxalate and hence increased urinary concentration of oxalate. It was previously thought that dietary oxalate accounted for little of the oxalate in the urine (<10%), but Holmes et al showed that between 24% and 53% | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. hyperoxaluria. Excess intake of foods high in oxalate including chocolate, cocoa, leafy greens (especially rhubarb and spinach), black tea, nuts, peanut butter, or starfruit may lead to elevated plasma concentration of oxalate and hence increased urinary concentration of oxalate. It was previously thought that dietary oxalate accounted for little of the oxalate in the urine (<10%), but Holmes et al showed that between 24% and 53% of urinary oxalate is attributable to oxalate from the diet . Therapy consists of dietary oxalate restriction and use of calcium carbonate or calcium citrate at meal times to bind dietary oxalate .Idiopathic calcium oxalate urolithiasis is associated with "mild metabolic hyperoxaluria." Features that often differentiate this condition from PH1:Lower urinary oxalate excretionLess severe stone diseaseThe hyperoxaluria rarely leads to ESRD.Tendency to hypercalciuria (as opposed to hypocalciuria in | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. al showed that between 24% and 53% of urinary oxalate is attributable to oxalate from the diet . Therapy consists of dietary oxalate restriction and use of calcium carbonate or calcium citrate at meal times to bind dietary oxalate .Idiopathic calcium oxalate urolithiasis is associated with "mild metabolic hyperoxaluria." Features that often differentiate this condition from PH1:Lower urinary oxalate excretionLess severe stone diseaseThe hyperoxaluria rarely leads to ESRD.Tendency to hypercalciuria (as opposed to hypocalciuria in PH1)Day-to-day variability in the levels of urinary oxalate excretion (in contrast to PH1, in which levels are persistently elevated in the urine )Dent disease. The clinical features of Dent disease may overlap those of PH1. Both are associated with nephrocalcinosis and urolithiasis in childhood and progress to renal failure (see Table 3).Table 3. Clinical and Diagnostic Features of Dent Disease and Primary Hyperoxaluria Type 1 | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. uria (as opposed to hypocalciuria in PH1)Day-to-day variability in the levels of urinary oxalate excretion (in contrast to PH1, in which levels are persistently elevated in the urine )Dent disease. The clinical features of Dent disease may overlap those of PH1. Both are associated with nephrocalcinosis and urolithiasis in childhood and progress to renal failure (see Table 3).Table 3. Clinical and Diagnostic Features of Dent Disease and Primary Hyperoxaluria Type 1View in own windowClinical and Diagnostic FeaturesDent DiseasePH1Nephrocalcinosis3+2+Urolithiasis3+4+Osteodystrophy1+1+ 1Renal failure2+2+Hypercalciuria1+—Hyperoxaluria—3+Low-molecular-weight proteinuria1+— 2GeneCLCN5AGXTInheritanceX linkedAutosomal recessiveFrom Milliner 1. After renal failure | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. Dent Disease and Primary Hyperoxaluria Type 1View in own windowClinical and Diagnostic FeaturesDent DiseasePH1Nephrocalcinosis3+2+Urolithiasis3+4+Osteodystrophy1+1+ 1Renal failure2+2+Hypercalciuria1+—Hyperoxaluria—3+Low-molecular-weight proteinuria1+— 2GeneCLCN5AGXTInheritanceX linkedAutosomal recessiveFrom Milliner 1. After renal failure established2. May be observed following renal damage but not an early or characteristic findingOther hereditary causes of kidney stones. A number of common and rare forms of nephrocalcinosis or urolithiasis may be associated with kidney disease .Another condition that may present with findings of nephrolcalcinosis is familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) (OMIM 248250).While not associated with | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. om Milliner 1. After renal failure established2. May be observed following renal damage but not an early or characteristic findingOther hereditary causes of kidney stones. A number of common and rare forms of nephrocalcinosis or urolithiasis may be associated with kidney disease .Another condition that may present with findings of nephrolcalcinosis is familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) (OMIM 248250).While not associated with nephrocalcinosis, children with adenine phosphoribosyltransferase (APRT) deficiency (OMIM 614723) can develop crystal nephropathy and chronic kidney disease, as do children with PH1. Hyperoxaluria is not a feature of APRT deficiency, though 2,8-dihydroxyadenine (DHA) crystals in kidney tissue can resemble those of calcium oxalate.Other. Acute renal failure secondary to oxalate deposition in the kidneys has occurred in persons taking large doses | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1283/ | j4Rg9gA | Primary Hyperoxaluria Type 1 | C0268164 | 18 | primary hyperoxaluria type 1. 248250).While not associated with nephrocalcinosis, children with adenine phosphoribosyltransferase (APRT) deficiency (OMIM 614723) can develop crystal nephropathy and chronic kidney disease, as do children with PH1. Hyperoxaluria is not a feature of APRT deficiency, though 2,8-dihydroxyadenine (DHA) crystals in kidney tissue can resemble those of calcium oxalate.Other. Acute renal failure secondary to oxalate deposition in the kidneys has occurred in persons taking large doses ("megadoses") of ascorbic acid (vitamin C) as well as in a number of persons who were "juicing" (extraction of juice from vegetables or fruit) with high oxalate-containing foods .Ingestion of ethylene glycol, an oxalate precursor, can lead to excess production and increased concentrations of oxalate in both the plasma and urine .Hyperoxaluria in association with total parenteral nutrition has been described in premature infants and adults .Hyper | [
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