Gyrate atrophy of the choroid and retina is an autosomal recessive chorioretinal dystrophy which leads to a slowly progressive loss of vision. The primary defect is due to a deficiency of the
enzyme ornithine delta-
aminotransferase, which is responsible for markedly elevated levels of
ornithine in plasma and other body fluids. Although several therapeutic regimens have been proposed, the reduction in
ornithine accumulation obtained by reducing the intake of its precursor
arginine (semisynthetic low-
arginine diet) is the one most practised. In this clinical and molecular study we report a patient with hyperornithinaemia and
gyrate atrophy of the choroid and retina who had been diagnosed when she was 3 years 9 months old. She also presented mild
mental retardation, delayed language development and speech defects. The patient has recently been found to be homozygous for the new Gly91Arg amino acid substitution of the
enzyme ornithine delta-
aminotransferase. This mutation lies in a region of the mature
protein that is considered crucial for the mitochondrial targeting activity. In this patient, a 28-year treatment with a completely natural
low-protein diet (0.8 g/kg per day of natural
protein) has been able to significantly reduce
ornithine plasma levels, and to greatly delay the natural progression of the chorioretinal changes. This study suggests that, in the long-term treatment of
gyrate atrophy, the efficacy in slowing the progression of chorioretinal changes and the palatability of a completely natural
low-protein diet make this treatment a potentially viable alternative in patients refusing the semisynthetic diet.