Andreas Schulze MD PhD (

Dr. Schulze of the University of Toronto and Section Head, Metabolic Genetics, and Medical Director, Newborn Screening Program, The Hospital for Sick Children, has no relevant financial relationships to disclose.

Tyler Reimschisel MD, editor. (Dr. Reimschisel of Vanderbilt University has received contracted research grants from Shire.)
Originally released April 24, 2006; last updated June 3, 2019; expires June 3, 2022

This article includes discussion of hyperornithinemia, atrophia gyrata, and gyrate atrophy of the choroid and retina. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.


Slowly progressive ophthalmological changes beginning in childhood and leading to blindness in the fifth decade are the characteristics of gyrate atrophy of the choroid and retina. Gyrate atrophy is an inherited metabolic disease that is caused by deficiency of the enzyme ornithine aminotransferase. The biochemical hallmark of the disease is the distinctly increased amino acid ornithine in plasma. In this article, the author provides an in-depth review of the clinical presentation, pathophysiology, diagnosis, and treatment options for gyrate atrophy.

Key points


• Hyperornithinemia is a slowly progressive disease, primarily of the eyes, with visual deterioration starting in late childhood and blindness around the fifth decade of life.


• It is an autosomal-recessive inborn error of metabolism due to deficiency of the enzyme ornithine aminotransferase.


• Chorioretinal degeneration and hyperornithinemia are diagnostic for the disease.


• Except for a few cases that respond to vitamin B6, treatment is strict protein restriction and supplementation of arginine-free amino acid mixture.


• Successful reduction of ornithine halts the progression of the disease.

Historical note and terminology

The report of a case of "atypical retinitis pigmentosa" by Jacobsohn in 1888 represents probably the first description of a patient with gyrate atrophy of the choroid and retina, as defined by the characteristic appearance of the ocular fundus and a typical history of visual deterioration (Jacobsohn 1888). Cutler in 1895 and Fuchs in 1896 were the first ophthalmologists to recognize this condition as a distinct entity (Cutler 1895; Fuchs 1896). Fuchs gave the disorder its euphonious appellation. Usher reviewed 26 cases in 1935, emphasizing the genetic aspects (Usher 1935). Despite of the observation in 1960 of an abnormally large lysine-ornithine spot in the urine of a patient with gyrate atrophy, hyperornithinemia and ornithinuria were not recognized as the biochemical counterparts of this disorder (Kurstjens 1965) until the report of Simell and Takki in 1973 (85 years after the initial ophthalmologic description). They postulated that the hyperornithinemia was presumably due to deficiency of ornithine aminotransferase (OAT) in 9 patients with gyrate atrophy of the choroid and retina (Simell and Takki 1973).

Ornithine aminotransferase was first described in animal tissues by Quastel and Witty and Meister (Quastel and Witty 1951; Meister 1954). The deficiency of the ornithine aminotransferase in a patient with gyrate atrophy was first demonstrated by Valle and colleagues (Valle et al 1977). Mitchell and colleagues identified the first mutations in the ornithine aminotransferase gene of patients with gyrate atrophy (Mitchell et al 1988). The quantitative importance of the ornithine aminotransferase transamination reaction in the regulation of ornithine homeostasis was first proven by Seiler and colleagues (Seiler et al 1989).

To elucidate the pathophysiology of the disease, animal models were implemented by initially using intravitreal injection of L-ornithine (Kuwabara et al 1981) and later application of 5FMOrn as selective ornithine aminotransferase inhibitor (Daune-Anglard et al 1993). Since 1995, the transgenic mouse model for ornithine aminotransferase deficiency has provided an opportunity to glean deeper insights (Wang et al 1995). The retarded hair growth (rhg) mutant mouse may offer an ideal model for gyrate atrophy of the choroid and retina in humans. This mouse mutant is caused by the same missense mutation that is known in some families (Bisaillon et al 2014).

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