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Am J Hum Genet. 1989 March; 44(3): 344–352. | PMCID: PMC1715442 |
Gyrate atrophy of the choroid and retina: characterization of mutant ornithine aminotransferase and mechanism of response to vitamin B6. N G Kennaway, L Stankova, M K Wirtz, and R G Weleber Department of Medical Genetics, Oregon Health Sciences University, Portland 97201. Abstract The purpose of this study was to characterize the mutant enzyme in nine patients with gyrate atrophy of the choroid and retina associated with ornithine aminotransferase (OAT) deficiency, to elucidate the mechanism of response to pyridoxine in four pyridoxine-responsive patients, and to determine the extent of genetic heterogeneity in both groups of patients. We have measured the apparent Km for pyridoxal phosphate (PLP) in fibroblast mitochondria and the heat stability of OAT at 45 degrees C in the presence and absence of PLP, using a sensitive radiochemical assay. The apparent Km for PLP was higher in pyridoxine-responsive patients than in nonresponsive patients whose apparent Km for PLP was normal. In contrast, the apparent Km for ornithine was normal in the seven patients studied. Surprisingly, the responsive patient with mildest clinical disease had the highest Km for PLP. However, she had the most stable enzyme, which presumably contributed to her milder phenotype. Western blot analyses of mitochondrial proteins, using antibody to human OAT, indicated clearly detectable OAT protein in pyridoxine-responsive patients and in two of five nonresponders, but low or undetectable levels in the other three patients. These data clarify the mechanism of pyridoxine response and indicate heterogeneity within as well as between the pyridoxine-responsive and the nonresponsive patients with gyrate atrophy. Full text Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.4M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References. Images in this article Click on the image to see a larger version. These references are in PubMed. This may not be the complete list of references from this article. - Hayasaka S, Saito T, Nakajima H, Takaku Y, Shiono T, Mizuno K, Ohmura K, Tada K. Gyrate atrophy with hyperornithinaemia: different types of responsiveness to vitamin B6. Br J Ophthalmol. 1981 Jul;65(7):478–483. [PubMed]
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