OMIM ID:
Hyperoxaluria, Primary, Type I
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
About 30% of patients with type I develop retinopathy and about half of those have a diffuse optic atrophy. Oxalate crystal deposition can cause a ‘fleck retina’ picture sometimes described as a crystalline retinopathy. There is wide variation in the retinal phenotype. Retinal toxicity leads to early and progressive vision loss. The RPE may respond with hyperpigmentation in the form of 'ringlets' in the posterior pole. Retinal fibrosis has been described. Some patients develop choroidal neovascularization.
Evaluation using EDI-OCT shows progressive deposition of oxalate crystals throughout the retina, pigment epiithelium, and choroid.
Systemic Features
The onset of this disease can occur any time from infancy to 25 years of age. Failure to thrive can be a presenting sign in infants. Most patients have glycolic aciduria and hyperoxaluria as the result of failure to transaminate glyoxylate to form glycine. The result is deposition of insoluble oxalate crystals in various body tissues with nephrolithiasis and nephrocalcinosis often early signs. Neurologic, cardiac, vascular, and kidney disease is often the result although oxalate crystals can be found throughout the body. Arteriole occlusive disease may lead to gangrene, Raynaud phenomena, acrocyanosis and intermittent claudication. Renal failure is common.
Genetics
Inheritance
Hyperoxaluria type I is an autosomal recessive disorder resulting from a mutation in the alanine-glyoxylate aminotransferase gene (AGXT) located at 2q36-q37. Failure of this liver peroxisomal enzyme to transaminate glyoxylate results in oxidation of this molecule to form oxalate.
Hyperoxaluria type II (260000) is caused by mutations in the GRHPR gene (9cen) and type III (613616) by mutations in DHDPSL (HOGA1) (10q24.2). Urolithiasis is the only clinical feature in these types.
Pedigree
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.