Muscle creatine phosphate in gyrate atrophy of the choroid and retina withhyperornithinaemia-clues to pathogenesis

Background In gyrate atrophy of the choroid and retina with hyperornithinae mia (GA), inherited deficiency of ornithine-delta-aminotransferase leads to progressive fundus destruction and atrophy of type II skeletal muscle fibr es. Because high ornithine concentrations inhibit creatine biosynthesis, th e ensuing deficiency of high-energy creatine phosphate may mediate the path ogenesis. Materials and methods Relative concentrations of inorganic phosphate (P-i), creatine phosphate (PCr) and ATP in resting calf muscle were recorded in 2 3 GA patients and 33 control subjects using P-31-magnetic resonance spectro scopy (MRS). Eight patients with autosomal recessive retinitis pigmentosa w ith matched control subjects constituted an additional reference group. Results The PCr/P-i and PCr/ATP ratios (means +/- SD) were lower for the GA patients than for healthy control subjects [4.66 +/- 0.37 vs. 9.75 +/- 2.1 7 (P < 0.0001) and 2.85 +/- 0.37 vs. 3.70 +/- 0.50 (P < 0.05) respectively] . In retinitis pigmentosa the respective values were 9.12 +/- 2.57 and 4.25 +/- 0.45. Age and stage of the disease had no effect. Conclusion Muscle P-31-MRS spectra were markedly abnormal in all GA patient s.