Hypoxanthine-Guanine Phosphoribosyltransferase Deficiency: Biochemical and Molecular Findings in Six Argentine Patients

Abstract

Hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency is an inborn error of purine metabolism responsible for Lesch-Nyhan Disease (LND) and its partial phenotypes, HPRT-related hyperuricemia with neurologic dysfunction (HRND) and hyperuricemia alone. We report here the recognition of six Argentine patients, two with LND and four with HRND. All patients presented elevated excretion of uric acid, hypoxanthine, and xanthine and decreased HPRT enzyme activities <1 nmol/h/mg Hb. The molecular analysis demonstrated in the two LND patients a novel inherited transition mutation, c.203T >C (L68P), in one subject and a germline transition mutation, c.209G >A (G70E), in the other. In the HRND patients a novel transversion mutation, c.584 A >C (Y195S), was found in three related patients and an inherited transition mutation, c.143G >A (R48H), in the fourth subject.

Keywords:

• HPRT
• hypoxanthine-guanine phosphoribosyltransferase deficiency
• Lesch-Nyhan disease
• Lesch-Nyhan variant
• HPRT mutation

Acknowledgments

This research was supported by grants from the Lesch-Nyhan Syndrome Children's Research Foundation (USA), and SECYT, UNC (Argentina). The DNA sequencing was performed in the Vermont Cancer Center DNA Analysis Facility and we thank Tim Hunter for expediting the sequencing process.