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In gyrate atrophy of the choroid and retina with hyperornithinaemia (GA), a genetically determined deficiency of ornithine delta-aminotransferase activity leads to high ornithine concentrations in body fluids. GA is characterized by centripetally progressing retinal and choroidal destruction and selective atrophy with tubular aggregates in type II skeletal muscle fibres. These findings have been suggested to be mediated by hyperornithinaemia-induced deficiency of high-energy creatine phosphate. As abnormal brain magnetic resonance images and electroencephalograms are found in another disorder of creatine metabolism, guanidinoacetate methyltransferase deficiency, we investigated the central nervous system involvement in GA, which seems to be associated with a milder degree of phosphocreatine deficiency. We compared 23 untreated GA patients with age-matched healthy controls, and with 9 patients who had received creatine or creatine precursor supplementation daily for several years. The mean age of the patients (32 +/- 18 years) was similar to that of the controls (36 +/- 22 years). The MRI or EEG findings of the patients on creatine supplementation did not differ from those of the untreated group. Brain MRI revealed degenerative lesions in the white matter in 50% of the GA patients, and 70% of the patients had premature atrophic changes, with a striking increase in the number of Virchow's spaces. Of the patients whose EEG was recorded, 58% had abnormal slow background activity, focal lesions or high-amplitude beta rhythm (50 microV). The EEG findings were not associated with the MRI changes or with the age or the sex of the patients. Early degenerative and atrophic brain changes and abnormal EEG are thus features of GA, in addition to the well-characterized eye and muscle manifestations.

Gyrate atrophy of the choroid and retina with hyperornithinaemia (GA), an autosomal recessive disease, affects skeletal muscle in addition to the eye. Muscle biopsy samples show prominent type 2 muscle fibre atrophy. Atrophic fibres also contain accumulations of tubular aggregates in electron microscopy. To evaluate skeletal muscle involvement in detail, the thigh muscles of 7 patients with GA were examined using semi-open conchotome muscle biopsies, computed tomography (CT) and ultralow-field magnetic resonance imaging (MRI) at 0.02 T. In MRI, the T1 and T2 proton relaxation times were measured. Type 2 muscle fibre atrophy was found in all biopsy samples (100%) and tubular aggregates in 6 of the 7 samples studied (87%). The CT density of the muscle tissue was increased in the only child of the study, decreased in 3 elderly subjects, and normal in the remaining 3 patients. Mean T1 relaxation times of the patients were decreased (135 +/- 5 ms) as compared to those of 6 healthy controls (157 +/- 12 ms) (p = 0.002). The T2 relaxation time was slightly increased (40 +/- 3 ms) as compared to the controls (35 +/- 7 ms; not significant, p = 0.3). Our findings suggest that the thigh muscles of the patients with GA universally show changes in CT and MRI studies, but relaxation time measurements gave little additional information on the muscle metabolism.