Pyridoxine-responsive gyrate atrophy of the choroid and retina: Clinical and biochemical correlates of the mutation A226V

We discovered the missense mutation, A226V, in the ornithine-δ- aminotransferase (OAT) genes of two unrelated patients with gyrate atrophy of the choroid and retina (GA). One patient, who was a compound for A226V and for the premature termination allele R398ter, showed a significant (P < .01) decrease in mean plasma ornithine levels, following pyridoxine supplementation with a constant protein intake: 826 ± 128 μM (4 = 5; no pyridoxine supplementation) versus 504 ± 112 μM (n = 6; 500 mg pyridoxine/d) and 546 ± 19 μM (n = 6; 1,000 mg pyridoxine/d). In extracts of fibroblasts from a second GA patient homozygous for A226V and from Chinese hamster ovary cells expressing an OAT-cDNA-containing A226V, we found that OAT activity increased from undetectable levels to ~10% of normal when the concentration of pyridoxal phosphate was increased from 50 to 600 μM. A226V is the fourth disease-causing pyridoxine-responsive human mutation to be reported.