99 LATE ONSET EPISODIC LOSS OF CONSCIOUSNESS IN PATIENTS WITH COUT AND HYPOXANTHINE CUANINE PHOSPHORIBOSYL TRANSFERASE (HPRT) DEFICIENCY: ?ASSOCIATED WITH MARKEDLY RAISED CEREBROSPINAL FLUID (CSF) HYPOXANITHINE CONCENTRATIONS

Abstract

Two men (ages 24 and 45) with gout and HPRT deficiency (RBC extracts <1% normal) but no previous evidence of neurolcgical disturbatice began to develop episodes of loss of consciousness without movement disorder 19 and 22 years after starting treatment with allopurinol. Cardiovascular and neurological examination were normal, as were EOGs, EEGs, CT scans and plasma glucose, electrolytes, urate and creatinine. CSF amino acid concentrations were normal. HPLC measurements of CSF and plasma purines off allopurinol therapy are shown in the table.As in previous studies of CSF oxypurines in Lesch-Nyhan syndrome CSF hypoxaithine concentrations were 4-6 fold higher than those in plasma suggesting local CNS production. Brain eventrations of hypoxanthine may be high enough in patients with gout and HPRT deficiency to trigger seizures by interfering with diazepam receptor biiiding and gamma-amniobutyric acid (GABA) function1,2