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 K(m) for pyridoxal phosphate (PLP) in fibroblast mitochondria and the heat stability of OAT at 45°C in the presence and absence of PLP, using a sensitive radiochemical assay. The apparent K(m) for PLP was higher in pyridoxine-responsive patients than in nonresponsive patients whose apparent K(m) for PLP was normal. In contrast, the apparent K(m) for ornithine was normal in the seven patients studied. Surprisingly, the responsive patient with mildest clinical disease had the highest K(m) 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.
|Original language||English (US)|
|Number of pages||9|
|Journal||American Journal of Human Genetics|
|State||Published - 1989|
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