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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. 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.
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.
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.
Some patients benefit from oral pyridoxine (B6) treatment in type I hyperoxaluria. Renal transplantation by itself is only temporarily helpful since the enzymatic defect remains and the donor tissue becomes damaged as well. Combined renal-liver transplantation should be considered instead because it corrects the primary metabolic error and can even reverse the accumulation of oxalate crystals.
North Carolina macular dystrophy is characterized by central macular defects that are present at birth but rarely progress. The fundus findings are highly variable and are usually more dramatic than expected from the visual acuity, which ranges from 20/40 to 20/200, with an average around 20/50. The clinical findings have been classified into different grades: In Grade I, fine drusen-like lesions at the level of the retinal pigmented epithelium are found in the central macular area. Grade II exhibits central confluent drusen with or without pigmentary changes, retinal pigment epithelium atrophy, disciform scar formation or neovascularization. Grade III is characterized by a well-delineated chorioretinal degeneration with hyperpigmentation at the border of the lesion. A central crater-like lesion that affects all retinal layers, as well as the deep choroidal tissue, is a typical finding. It is surrounded by an elevated ridge, which is 3-4 disc diameter is diameter. Color vision and electrophysiological testing are usually normal.
Although first described in a 4 generation North Carolina family, it has since been found in a variety of ethnic groups and geographic locations.
No general systemic manifestations are associated with North Carolina macular dystrophy.
North Carolina macular dystrophy is an autosomal dominant disorder with high penetration. The genetic locus for the disorder is designated MCDR1, for macular degeneration locus 1, and has been mapped to 6q14-q16.2. Candidate genes in this region have been screened for disease causing mutations, but none have been identified so far. The disorder was initially described in a family of Irish descent in North Carolina, and affected individuals have been identified in European, Asian and South American families as well.
For patients with Grade II disease with choroidal neovascularization, standard treatment for neovascularization may be used. Low vision aids can be useful for other forms of the disorder with decreased visual acuity.