Abstract
GA patients exhibit chorioretinal degeneration and histologic muscle abnormalities. Owing to an inherited deficiency of ornithine aminotransferase, they accumulate ornithine to levels which are 10× normal and well above the Ki of glycine transamidinase, the first enzyme in the creatine biosynthetic pathway. Previous work utilizing an insensitive assay has shown reduced levels of the creatine (cr) presursor guanidinoacetic acid (gaa) in the urine of patients with GA (Sipila et al, J.Clin.Invest. 67: 1805,1981). We developed a specific HPLC/fluorometric method for measuring these compounds in biologic samples. The lower limit of detectability for cr is 0.1 pmol and for gaa 3 pmol. We found subnormal levels of both cr and gaa in patients with GA.
In addition, we found reduced levels of total cr in adult GA skeletal muscle: patients (n=3) mean (range) is 6.5 nmol/mg prot (5.1-7.8); control (n=3) 31.4 (23.5-42.0). We conclude from the reduced levels of gaa that cr synthesis is impaired in GA and that this eventually leads to reduction of tissue levels of cr despite normal dietary intake. These results support the hypothesis that cr deficiency is an important pathophysiologic factor in GA.
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Sipila, I., Valle, D., Brusilow, S. et al. DEFECTIVE CREATINE METABOLISM IN GYRATE ATROPHY OF THE CHOROID AND RETINA (GA). Pediatr Res 18 (Suppl 4), 226 (1984). https://doi.org/10.1203/00006450-198404001-00798
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DOI: https://doi.org/10.1203/00006450-198404001-00798