Reduced brain creatine in gyrate atrophy of the choroid and retina with hyperornithinemia

Objective: To analyze in vivo brain creatine (Cr) content in gyrate atrophy of the choroid and retina with hyperornithinemia (GA). Background: GA is caused by inherited deficiency of ornithine-delta-aminotransferase activity. Patients lose their vision by middle age and develop selective atrophy of type II skeletal muscle fibers. As demonstrated by MRS, the patients' skeletal muscles have diminished stores of high-energy Cr phosphate. Minor structural and electrophysiologic abnormalities in the brain of these patients also imply that the CNS may be affected, Methods: The authors acquired proton MR spectra of the basal ganglia of 22 healthy control subjects and 20 GA patients. Nine patients received supplementary Cr or its precursors, and one child was on an arginine-restricted diet to normalize plasma ornithine concentration. The ratios of N-acetylaspartate (NAA) to Cr, NAA to choline (Cho), and Cho to Cr, and the ratios of NAA, Cho, and Cr to tissue water were calculated. Results: NAA/Cr (Cho/Cr) in the untreated and treated patients and control subjects were (mean +/- SD) 3.3 +/- 0.4, 2.0 +/- 0.4, and 1.5 +/- 0.7 (1.9 +/- 0.3, 1.3 +/- 0.4, and 0.9 +/- 0.2), indicating that Cr content in untreated GA patients was proportionally and markedly diminished, and partially corrected by therapy (p < 0.0001). NAA/Cho was similar in all three groups. Cr/water in the untreated patients was only 46%, and increased to 75% of the control ratios in the treated patients (p < 0.0001). Conclusions: Hyperornithinemia-associated Cr deficiency in GA also affects the CNS, further supporting the possibility that Cr deficiency also has a pathogenetic role in the retina. The deficiency was partially corrected by Cr supplementation and an arginine-restricted diet.