ABSTRACT
The overactivity of PRPP synthetase is transmitted as a sex-linked abnormality, being characterized by uric acid overproduction and, in some patients, by muscular hypotonia, neurosensitive deafness and/or ataxia. The pathogenesis of these neurologic abnormalities is not yet known. The CSF concentrations of end products of the neuronal metabolism of purines--hypoxanthine for the adenine nucleotides and xanthine for guanine nucleotides--have not been previously studied in patients with overactivity of PRPP synthetase. We have evaluated the plasma and CSF levels of hypoxanthine and xanthine in a 8-year-old male with tophaceous gout and neurosensitive deafness and in his mother, who had gout without neurological involvement. PRPP synthetase overactivity was demonstrated in fibroblast culture; the male was hemizygote and his mother was heterozygotic. In 4 normal individuals, the plasma levels of hypoxanthine and xanthine were 1.7 +/- 0.4 microM and 0.9 +/- 0.2 microM (mean +/- SEM), respectively, while in in CSF they were 3.3 +/- 1.1 microM and 2.0 +/- 0.2 microM. The hemizygote male showed a considerable increase in hypoxanthine level (5.6 microM in plasma and 22.1 microM in CSF); the plasma and CSF xanthine levels were 1.8 and 4.5 microM, respectively. The heterozygotic female showed moderately increased plasma hypoxanthine levels (3.9 and 10.6 microM) and normal xanthine levels (1.3 and 1.8 microM). These results suggest an increase in the degradation of purine nucleotides in the central nervous system of patients with PRPP synthetase overactivity and neurological symptoms. The predominance of hypoxanthine over xanthine may indicate a greater increase of the degradation of adenine rather than guanine nucleotides.
