Central nervous system involvement in gyrate atrophy of the choroid and retina with hyperornithinaemia

In gyrate atrophy of the choroid and retina with hyperornithinaemia (GA), a genetically determined deficiency of ornithine delta-aminotransferase acti vity leads to high ornithine concentrations in body fluids. GA is character ized by centripetally progressing retinal and choroidal destruction and sel ective atrophy with tubular aggregates in type II skeletal muscle fibres. T hese findings have been suggested to be mediated by hyperornithinaemia-indu ced deficiency of high-energy creatine phosphate. As abnormal brain magneti c resonance images and electroencephalograms are found in another disorder of creatine metabolism, guanidinoacetate methyltransferase deficiency, we i nvestigated 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 pat ients who had received creatine or creatine precursor supplementation daily for several years. The mean age of the patients (32 +/- 18 years) was simi lar to that of the controls (36 +/- 22 years). The MRI or EEG findings of t he patients on creatine supplementation did not differ from those of the un treated group. Brain MRI revealed degenerative lesions in the white matter in 50% of the GA patients, and 70% of the patients had premature atrophic c hanges, 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 mu V). 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 ar e thus features of GA, in addition to the well-characterized eye and muscle manifestations.