Gyrate atrophy is a rare hereditary disease of the eye's retina (the layer of
light-sensitive tissue that lines the inside of the eyeball) and choroid (a vascular layer
of tissue behind the retina). Degeneration of these structures causes near-sightedness,
cataracts and progressive loss of vision. This study will examine eye function and chemical
and molecular abnormalities in patients with gyrate atrophy to try to better understand,
diagnose, and treat the condition. Patients with other degenerative diseases of the choroid
and retina, such as retinitis pigmentosa, choroideremia, and others, will also be studied
for comparison. Family members of patients will be studied, when possible, to try to
identify the genetic basis of the disease and gain information that will aid in genetic
Study participants will undergo a physical examination and eye examination, including tests
of color vision, field of vision, and ability to see in the dark. An electroretinogram and
electrooculogram will measure visual cell function. Photographs of the retina will be
taken. Blood will be drawn for biochemical study and gene research. Family members who
agree to participate in the study will undergo the same eye tests and will also have blood
drawn for genetic studies. Patients with gyrate atrophy will also be asked to undergo a
small skin biopsy for biochemical and genetic study. They will provide a family history in
order to draw a family tree showing how the disease is distributed among family members.
Patients with gyrate atrophy may also participate in studies of the effect of vitamin B6 and
diet on blood levels of the amino acid ornithine, which is elevated in patients with gyrate
atrophy. Participants will take 500 mg of vitamin B6 by mouth every day for 3 to 6 months.
If this study confirms a reduction of ornithine levels, then long-term studies of the
vitamin as a possible treatment for the disease may be started.
After the vitamin B6 study, patients will start a nearly protein-free diet to lower
ornithine blood levels. More than 2,000 calories are carbohydrate and fat. Some special
low-protein foods and limited fruit is included, plus amino acid supplements. Patients who
have carefully adhered to this diet have lowered their ornithine levels and slowed disease
progression. Patients will be hospitalized for the first 1 to 3 weeks for close monitoring
with frequent urine and blood tests. When the blood ornithine level is normalized, a less
restricted low protein diet will be prescribed. Participants will have monthly blood tests
and a complete eye examination every 6 months to 1 year to evaluate disease progression.
Gyrate atrophy of the choroid and retina (GA) is a rare autosomal recessive chorioretinal
degeneration characterized by myopia, cataract, varying degrees of night blindness, and
progressive constriction of visual fields associated with chorioretinal atrophy resulting in
blindness. The objectives of this protocol are threefold:
1. Document the natural history of gyrate atrophy.
2. Relate the clinical course to the gene defect to explore the genetic heterogeneity
inherent in this disease.
3. Assess the clinical course and laboratory findings of the effects of an
arginine-deficient diet. The study population is patients with elevated plasma
ornithine and absence of ornithine-delta-aminotransferase activity. This is a natural
history study, with a nested intervention study, non-randomized, with the outcome
parameters being psychophysical, electrophysiological and ophthalmoscopic examination.
Patients must have hyperornithemia and a deficiency of OAT activity to enter the study.