Purine and pyridine nucleotide metabolism in the erythrocytes of patients with Rett syndrome.

The possible involvement of purine and pyridine metabolism in Rett syndrome, a neurodegenerative disorder of unknown aetiology affecting females, was investigated. The levels of purine and pyridine nucleotides and their metabolites were determined by HPLC in the erythrocytes and plasma of 31 Rett patients and of 17 age-matched controls. Nucleotide production rate from extracellular precursors was determined in intact cells and enzyme activities were assayed in crude lysates using the same HPLC method. Decreased plasma nicotinamide concentrations and lower erythrocyte activities of hypoxanthine phosphoribosyl transferase, adenine phosphoribosyl transferase and phosphoribosylpyrophosphate synthetase were observed in Rett children compared with age-matched controls, while the production rate of IMP from hypoxanthine and of total pyridine nucleotides from nicotinic acid by intact erythrocytes was significantly increased. No significant difference was found in any of the other parameters examined. These findings give a new contribution to the knowledge of the biochemical alterations in Rett syndrome and encourage further investigations in the nucleotide field.