Gyrate atrophy of the choroid and retina. Long-term reduction of ornithine slows retinal degeneration
M. I. Kaiser-Kupfer, R. C. Caruso and D. Valle
National Eye Institute, National Institutes of Health, Bethesda, MD 20892.
Gyrate atrophy of the choroid and retina is an autosomal recessive,
chorioretinal dystrophy that begins in childhood and leads to blindness in
the fourth to seventh decade of life. The primary defect is deficiency of
ornithine-delta-amino-transferase, which results in accumulation of
ornithine. We examined six pairs of affected siblings to determine if
intrafamilial variability in the phenotype was less than interfamilial, and
to determine if long-term (5- to 7-year) reduction of ornithine with an
arginine-restricted diet had an effect on the progression of the
chorioretinal degeneration. All but one set of siblings underwent periodic
ophthalmologic examinations. The clinical diagnosis was confirmed with the
demonstration of hyperornithinemia and deficiency of
ornithine-delta-aminotransferase. The molecular defects in their
ornithine-delta-amino-transferase genes also were determined. The two
younger pairs of siblings were given an arginine-restricted diet and
followed up for 5 to 7 years. We found strikingly similar phenotypes in
affected members of the same pair of siblings. In the young patients
receiving the diet, there was substantial reduction of ornithine levels.
These children had only modest progression of their ocular disease during
this period. Furthermore, a comparison of the outcome of the younger with
their older siblings at an equivalent age showed that the younger siblings,
who started receiving the diet at an earlier age, had much less ocular
disease. We conclude that intrafamilial phenotypic variation in gyrate
atrophy is less than interfamilial and, therefore, that genetic
heterogeneity plays a role in the phenotypic variability of gyrate atrophy.
Furthermore, we conclude that chronic reduction of ornithine with an
arginine-restricted diet dramatically slows the progression of the
chorioretinal dystrophy.
