Abstract
The end products of purine metabolism in the CNS are hypoxanthine for adenine nucleotides and xanthine for guanine nucleotides. Previous reports of two families with PRPP synthetase superactivity associated with neurodevelopmental defects have not documented metabolism of purines in the CNS. Fibroblasts extracts from an eight-year-old male with tophaceous gout and sensorineural deafness and from his mother with gout showed an aberrant PRPP synthetase characterized by resistance to purine nucleotide inhibition of enzyme activity. Hypoxanthine and xanthine concentrations in plasma and cerebrospinal fluid (CSF) were simultaneously measured by HPLC in both patients. In 4 normal subjects hypoxanthine and xanthine levels in plasma were (mean±SEM) 1.7±0.4 μM and 0.9±0.2 μM, respectively, and 3.3±1.1 and 2.0±0.2 μM in CSF. The hemizigous male showed a substantially increased hypoxanthine concentration of 5.6 μM in plasma and of 22.1 μM in CSF. Xanthine levels were 1.8 μM in plasma and 4.5 μM in CSF. The heterozigous female had moderately elevated plasma and CSF hypoxanthine concentrations (3.9 and 10.6 μM) and normal xanthine levels (1.3 and 1.8 μM).
These results suggest an increased purine nucleotide degradation in the CNS of patients with PRPP synthetase superactivity and neurological symptoms. The predominance of hypoxanthine over xanthine may indicate a relatively enhanced adenine nucleotide over guanine nucleotide degradation.
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Jiménez, M., Puig, J., Mateos, F. et al. 68 INCREASED PURINE NUCLEOTIDE DEGRADATION IN THE CENTRAL NERVOUS SYSTEM (CNS) IN PRPP SYNTHETASE SUPERACTIVITY. Pediatr Res 24, 122 (1988). https://doi.org/10.1203/00006450-198807000-00092
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DOI: https://doi.org/10.1203/00006450-198807000-00092