Gyrate Atrophy

Clinical Characteristics
Ocular Features: 

Gyrate atrophy is characterized by night blindness, myopia, and multiple round islands of peripheral chorioretinal degeneration which often appear in the first decade of life, sometimes as early as five years of age. Night blindness often begins in late childhood. The atrophic areas slowly progress to the posterior pole and may eventually affect central vision. Both eyes are usually symmetrically affected. All patients have myopia, some with refractive errors ranging up to -20 D. Fluorescein angiography shows hyperfluorescent at the edges of the peripheral atrophy. A zone of pigmentary changes can be seen between normal and atrophic areas.  The electroretinogram may show reduced rod and cone responses with rods affected more than cones in early phases. Dark-adapted ERG documents elevated rod thresholds.  Swollen mitochondria have been described in photoreceptors, corneal epithelium, and in the nonpigmented ciliary epithelium.  Elevated levels of ornithine are found in plasma, urine, spinal fluid and aqueous humor.  Macular edema is commonly present and posterior subcapsular cataracts requiring surgery are common.

Systemic Features: 

Mild muscle weakness may occur due to tubular aggregates in type 2 muscle fibers, which can be visualized with electron microscopy and may lead to loss of these fibers and muscle wasting. Fine, straight hairs have been observed with patches of alopecia. Slow wave background changes on EEG have been described in about one-third of patients and peripheral neuropathy is sometimes a feature.  Hearing loss has been described as well. Some newborns have a temporary elevation of plasma ammonia but once treated usually does not recur.

Genetics

Gyrate atrophy is an autosomal recessive disorder, caused by mutations in the OAT (ornithine aminotransferase) gene on chromosome 10 (10q26).  The enzyme is part of a nuclear-encoded mitochondrial matrix complex.  Many allelic variants have been found.  A large number of affected patients of Finnish origin, most of who share the common L402P mutation, have been described.

Treatment
Treatment Options: 

A low protein and especially an arginine-restricted diet have been shown to slow loss of function as measured by ERG and visual field changes.
 

References
Article Title: 

References

Kaiser-Kupfer MI, Caruso RC, Valle D, Reed GF. Use of an arginine-restricted
diet to slow progression of visual loss in patients with gyrate atrophy. Arch
Ophthalmol. 2004 Jul;122(7):982-4.

PubMedID: 15249361

Potter MJ, Berson EL. Diagnosis and treatment of gyrate atrophy. Int
Ophthalmol Clin. 1993 Spring;33(2):229-36. Review.

PubMedID: 8325736

Weleber RG, Kurz DE, Trzupek KM. Treatment of retinal and choroidal
degenerations and dystrophies: current status and prospects for gene-based
therapy. Ophthalmol Clin North Am. 2003 Dec;16(4):583-93, vii. Review.

PubMedID: 14740999

Brody LC, Mitchell GA, Obie C, Michaud J, Steel G, Fontaine G, Robert MF,
Sipila I, Kaiser-Kupfer M, Valle D. Ornithine delta-aminotransferase mutations in
gyrate atrophy. Allelic heterogeneity and functional consequences. J Biol Chem.
1992 Feb 15;267(5):3302-7.

PubMedID: 1737786