Primary hyperoxaluria, type I- MedGen UID:
- 75658
- •Concept ID:
- C0268164
- •
- Disease or Syndrome
Primary hyperoxaluria type 1 (PH1) is caused by deficiency of the liver peroxisomal enzyme alanine-glyoxylate aminotransferase (AGT), which catalyzes the conversion of glyoxylate to glycine. When AGT activity is reduced or absent, glyoxylate is converted to oxalate, which cannot be metabolized and must be excreted by the kidneys. Insoluble calcium oxalate crystals form due to high urinary oxalate concentration. Urinary crystals aggregate, leading to nephrolithiasis (i.e., calcium oxalate kidney stones) in the renal pelvis / urinary tract; often the crystals deposit in kidney parenchyma (nephrocalcinosis). The age at presentation of PH1 ranges from infancy (age <12 months) in 10% of individuals, childhood/adolescence (age 1-17 years) in 70%, and adulthood (age =18 years) in 20%. The natural history of untreated PH1 is (1) progressive decline in kidney function due to complications of nephrolithiasis (e.g., urinary obstruction, infection) and nephrocalcinosis, and (2) in persons with advanced chronic kidney disease (CKD), high plasma oxalate concentrations result in other organ and tissue damage from calcium oxalate deposition (i.e., "oxalosis"), most commonly in the bones, heart, and retina. In the absence of treatment, progression of oxalosis results in death from kidney failure and/or other organ involvement.
Primary hyperoxaluria, type II- MedGen UID:
- 120616
- •Concept ID:
- C0268165
- •
- Disease or Syndrome
Primary hyperoxaluria type 2 (PH2), caused by deficiency of the enzyme glyoxylate reductase/hydroxypyruvate reductase (GR/HPR), is characterized by recurrent nephrolithiasis (deposition of calcium oxalate in the renal pelvis / urinary tract), nephrocalcinosis (deposition of calcium oxalate in the renal parenchyma), and end-stage kidney disease (ESKD). After ESKD, oxalosis (widespread tissue deposition of calcium oxalate) usually develops. Symptom onset is typically in childhood.
Peroxisome biogenesis disorder 1B- MedGen UID:
- 79470
- •Concept ID:
- C0282527
- •
- Disease or Syndrome
Zellweger spectrum disorder (ZSD) is a phenotypic continuum ranging from severe to mild. While individual phenotypes (e.g., Zellweger syndrome [ZS], neonatal adrenoleukodystrophy [NALD], and infantile Refsum disease [IRD]) were described in the past before the biochemical and molecular bases of this spectrum were fully determined, the term "ZSD" is now used to refer to all individuals with a defect in one of the ZSD-PEX genes regardless of phenotype. Individuals with ZSD usually come to clinical attention in the newborn period or later in childhood. Affected newborns are hypotonic and feed poorly. They have distinctive facies, congenital malformations (neuronal migration defects associated with neonatal-onset seizures, renal cysts, and bony stippling [chondrodysplasia punctata] of the patella[e] and the long bones), and liver disease that can be severe. Infants with severe ZSD are significantly impaired and typically die during the first year of life, usually having made no developmental progress. Individuals with intermediate/milder ZSD do not have congenital malformations, but rather progressive peroxisome dysfunction variably manifest as sensory loss (secondary to retinal dystrophy and sensorineural hearing loss), neurologic involvement (ataxia, polyneuropathy, and leukodystrophy), liver dysfunction, adrenal insufficiency, and renal oxalate stones. While hypotonia and developmental delays are typical, intellect can be normal. Some have osteopenia; almost all have ameleogenesis imperfecta in the secondary teeth.
Primary hyperoxaluria type 3- MedGen UID:
- 462228
- •Concept ID:
- C3150878
- •
- Disease or Syndrome
Primary hyperoxaluria is an autosomal recessive disorder of glyoxylate metabolism that results in excessive endogenous oxalate synthesis and the formation of calcium oxalate kidney stones. Progressive renal inflammation and interstitial fibrosis from advanced nephrocalcinosis, recurrent urolithiasis, and urinary tract infections can cause reduced renal function, systemic oxalate deposition, and end-stage renal failure. Compared to hyperoxaluria type I (HP1; 259900) and type II (HP2; 260000), HP3 appears to be the least severe, with good preservation of kidney function in most patients. The typical clinical characteristic is early onset of recurrent urolithiasis, but less active stone formation later (summary by Wang et al., 2015).
For a discussion of genetic heterogeneity of primary hyperoxaluria, see 259900.
Nephrolithiasis susceptibility caused by SLC26A1- MedGen UID:
- 1830325
- •Concept ID:
- C5779632
- •
- Disease or Syndrome
Nephrolithiasis, calcium oxalate, 2, with or without nephrocalcinosis- MedGen UID:
- 1841152
- •Concept ID:
- C5830516
- •
- Disease or Syndrome
Calcium oxalate nephrolithiasis-2 with or without nephrocalcinosis (CAON2) is an autosomal dominant disorder of renal function characterized by the recurrent formation of CaOx kidney stones. The age at onset is highly variable, ranging from childhood to adult. Most affected individuals have concurrent nephrocalcinosis. Renal function is generally preserved (Majmundar et al., 2023).
See also CAON1 (167030).