BACKGROUND: Eye fundus destruction and type II muscle fiber atrophy in gyrate atrophy of the choroid and retina with hyperornithinaemia (GA) may be mediated by elevated ornithine concentrations which strongly inhibit creatine biosynthesis. This results in deficiency of creatine phosphate (PCr), a key intracellular energy source, as we have demonstrated in skeletal muscle of the patients by 31P magnetic resonance spectroscopy (31P MRS). MATERIALS AND METHODS: Possible correction of the relative PCr deficiency by long-term daily exogenous supplementation of creatine or its precursors was investigated in four GA patients receiving creatine and in five patients treated with guanidinoacetic acid-methionine combination. The relative PCr concentration, expressed as PCr/Pi (Pi; inorganic phosphate) or as PCr/ATP ratios, was compared with the values of untreated GA patients, and matched healthy volunteers. RESULTS: Muscle PCr/Pi ratios (mean +/- SD) of the untreated and creatine supplemented GA patients and controls were 4.9 +/- 1.4, 7.9 +/- 0.4 and 8.4 +/- 1.3. Guanidinoacetate-methionine combination was similarly effective (respective PCr/Pi ratios: 4.9 +/- 0.7, 6.3 +/- 1.1 and 10.7 +/- 2.8). CONCLUSION: Supplementation with creatine or creatine precursors almost normalised low muscle PCr/Pi ratios of patients with GA.
BACKGROUND: Eye fundus destruction and type II muscle fiber atrophy in gyrateatrophy of the choroid and retina with hyperornithinaemia (GA) may be mediated by elevated ornithine concentrations which strongly inhibit creatine biosynthesis. This results in deficiency of creatine phosphate (PCr), a key intracellular energy source, as we have demonstrated in skeletal muscle of the patients by 31P magnetic resonance spectroscopy (31P MRS). MATERIALS AND METHODS: Possible correction of the relative PCr deficiency by long-term daily exogenous supplementation of creatine or its precursors was investigated in four GA patients receiving creatine and in five patients treated with guanidinoacetic acid-methionine combination. The relative PCr concentration, expressed as PCr/Pi (Pi; inorganic phosphate) or as PCr/ATP ratios, was compared with the values of untreated GA patients, and matched healthy volunteers. RESULTS: Muscle PCr/Pi ratios (mean +/- SD) of the untreated and creatine supplemented GA patients and controls were 4.9 +/- 1.4, 7.9 +/- 0.4 and 8.4 +/- 1.3. Guanidinoacetate-methionine combination was similarly effective (respective PCr/Pi ratios: 4.9 +/- 0.7, 6.3 +/- 1.1 and 10.7 +/- 2.8). CONCLUSION: Supplementation with creatine or creatine precursors almost normalised low muscle PCr/Pi ratios of patients with GA.
Authors: M A Cleary; L Dorland; T J de Koning; B T Poll-The; M Duran; R Mandell; V E Shih; R Berger; S E Olpin; G T N Besley Journal: J Inherit Metab Dis Date: 2005 Impact factor: 4.982
Authors: Roberta R Alfieri; Mara A Bonelli; Andrea Cavazzoni; Maurizio Brigotti; Claudia Fumarola; Piero Sestili; Paola Mozzoni; Giuseppe De Palma; Antonio Mutti; Domenica Carnicelli; Federica Vacondio; Claudia Silva; Angelo F Borghetti; Kenneth P Wheeler; Pier Giorgio Petronini Journal: J Physiol Date: 2006-07-27 Impact factor: 5.182
Authors: Richard B Kreider; Charles Melton; Christopher J Rasmussen; Michael Greenwood; Stacy Lancaster; Edward C Cantler; Pervis Milnor; Anthony L Almada Journal: Mol Cell Biochem Date: 2003-02 Impact factor: 3.396
Authors: M Valtonen; K Näntö-Salonen; S Jääskeläinen; K Heinänen; A Alanen; O J Heinonen; N Lundbom; M Erkintalo; O Simell Journal: J Inherit Metab Dis Date: 1999-12 Impact factor: 4.982