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Gyrate atrophy of choroid and retina

ORPHA414
Synonym(s) HOGA
Hyperornithinemia
Hyperornithinemia - gyrate atrophy of choroid and retina
Ornithine aminotransferase deficiency
Prevalence Unknown
Inheritance Autosomal recessive
Age of onset Childhood
ICD-10
  • E72.4
OMIM
UMLS
  • C0599035
MeSH
  • C537132
MedDRA -

Summary

Gyrate atrophy of the choroid and retina (GACR) is a very rare, inherited retinal dystrophy, characterized by progressive chorioretinal atrophy, myopia and early cataract.

Prevalence has been estimated to be 1/50,000 in Finland. More than 200 biochemically-confirmed cases have been reported in the international literature. Cases have also been reported from Canada, Germany, Italy, Israel, Japan, the Netherlands and the USA.

Age at diagnosis is highly variable (1 month - 44 years). High phenotypic variability is noted among patients even within the same family, as well variable disease progression. The first complaints of the patients are night blindness (nyctalopia) and constriction of the visual field caused by multiple round areas of chorioretinal atrophy in the periphery. Over the years, the atrophic areas increase, coalesce and spread towards the macula leading to central visual loss in the 4th to 7th decade of life. Other ocular manifestations include myopia with marked astigmatism, early posterior subcapsular cataract, and cystoid macular edema.

GACR is caused by homozygous or compound heterozygous mutations in the ornithine aminotransferase OAT gene (10q26) which codes for the ornithine-degrading, pyridoxal phosphate-dependent enzyme ornithine aminotransferase. More than 60 OAT mutations have been identified to date. Deficient OAT enzyme activity results in hyperornithinemia. The exact mechanism leading to chorioretinal atrophy is still unknown.

Diagnosis is based on ophthalmological examination showing the typical sharply demarcated round patches of chorioretinal atrophy located circumferentially in the periphery, and the other clinical manifestations such as myopia and early cataract. Cystoid macular edema can be detected with optical coherence tomography. Fundus autofluorescence is absent in the atrophic areas. The full-field electroretinogram shows severely reduced or undetectable amplitudes even at an early stage of the disease. Serum, urine, and spinal fluid ornithine levels are 10 to 20 times higher than those in healthy subjects. The diagnosis can be confirmed by molecular genetic testing of the OAT gene.

Careful funduscopy, fundus autofluorescence images and pointed family history help to delimit autosomal recessive GACR from X-chromosomal choroideremia. At the slightest suspicion of GACR, serum ornithine levels should be measured to detect hyperornithinemia.

GACR follows an autosomal recessive pattern of inheritance. Genetic counseling should be provided to affected families.

Patients with GACR should be referred to a diet expert, because several studies report that an arginine-restricted diet (precursor of ornithine) or a low-protein diet may reduce the ornithine serum level and may slow the progression of chorioretinal atrophy and visual loss. Pyridoxine (vitamin B6) supplementation may also be given but most patients appear to be non-responsive. Cataract surgery may be required. In late stages with visual loss, magnifying visual devices should be provided.

The ocular prognosis is poor because constriction of the visual field and visual loss are progressive and can cause blindness. Early diagnosis and successful diet treatment are important prognostic factors.

Expert reviewer(s)

  • Dr Agnes RENNER

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