title: Low-protein diet and progression of retinal degeneration in gyrate atrophy of the choroid and retina: a twenty-six-year follow-up.
abstract: 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.
authors.affiliation: Department of Pediatrics, Second University of Naples, Naples, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Santinelli
authors.forename: C
authors.initials: C
authors.lastname: Costagliola
authors.forename: C
authors.initials: C
authors.lastname: Tolone
authors.forename: A
authors.initials: A
authors.lastname: D'Aloia
authors.forename: A
authors.initials: A
authors.lastname: D'Avanzo
authors.forename: F
authors.initials: F
authors.lastname: Prisco
authors.forename: L
authors.initials: L
authors.lastname: Perrone
authors.forename: E Miraglia
authors.initials: EM
authors.lastname: del Giudice
mesh_terms: D000328:Adult; D002675:Child, Preschool; D002829:Choroid / Q000473:pathology; D018753:Diet, Protein-Restricted; D004585:Electrooculography; D005260:Female; D005500:Follow-Up Studies; D015799:Gyrate Atrophy / Q000178:diet therapy* / Q000235:genetics / Q000473:pathology*; D006720:Homozygote; D006801:Humans; D009952:Ornithine / Q000097:blood; D009953:Ornithine-Oxo-Acid Transaminase / Q000235:genetics; D012160:Retina / Q000473:pathology; D012162:Retinal Degeneration / Q000178:diet therapy* / Q000235:genetics / Q000473:pathology*; D014794:Visual Fields
chemical_list: D009952:Ornithine; D009953:Ornithine-Oxo-Acid Transaminase