X-linked hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency in an inherited disorder of purine metabolism is usually associated with the clinical manifestations of hyperuricemia. A variable spectrum of neurological involvement occurs predominantly in males. Females are usually asymptomatic. Carrier status cannot be confirmed by biochemical and enzymatic methods reliably.
We studied clinical, biochemical and molecular genetic characteristics of Czech families with hyperuricemia and HPRT deficiency. We analyzed age at diagnosis, clinical symptoms, uricemia, urinary hypoxanthine and xanthine, HPRT activity in erythrocytes, mutation in the HPRT1 gene, X-inactivation, and major urate transporters.
A mutation in the HPRT1 gene in family A was confirmed in one boy and four females. Three females with hyperuricemia had normal excretion of purine. One female was normouricemic. An 8-month-old boy with neurological symptoms showed hyperuricemia, increased excretion of urinary hypoxanthine and xanthine and a very low HPRT activity in erythrocytes. We have found three other unrelated female carriers with hyperuricemia and normal excretion of hypoxanthine and xanthine among other families with HPRT deficiency.
HPRT deficiency needs to be considered in females with hyperuricemia with normal excretion of purine metabolites. Familiar hyperuricemia and/or nonfamiliar gout should always be further investigated, especially in children.