title: Hyperuricemia and gout due to deficiency of hypoxanthine-guanine phosphoribosyltransferase in female carriers: New insight to differential diagnosis.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Inherited Metabolic Disorders, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Kostalova
authors.affiliation: Institute of Rheumatology, Prague, Czech Republic.
authors.forename: Karel
authors.initials: K
authors.lastname: Pavelka
authors.affiliation: Institute of Inherited Metabolic Disorders, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic.
authors.forename: Hana
authors.initials: H
authors.lastname: Vlaskova
authors.forename: Dita
authors.initials: D
authors.lastname: Musalkova
authors.affiliation: Institute of Inherited Metabolic Disorders, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic; Institute of Rheumatology, Prague, Czech Republic. Electronic address: stiburkova@revma.cz.
authors.forename: Blanka
authors.initials: B
authors.lastname: Stiburkova
mesh_terms: D000328:Adult; D002648:Child; D003937:Diagnosis, Differential; D005260:Female; D006073:Gout / Q000209:etiology* / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D033461:Hyperuricemia / Q000175:diagnosis / Q000209:etiology*; D019271:Hypoxanthine / Q000652:urine; D007041:Hypoxanthine Phosphoribosyltransferase / Q000172:deficiency* / Q000235:genetics*; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D010375:Pedigree; D019820:Xanthine / Q000652:urine
chemical_list: D019820:Xanthine; D019271:Hypoxanthine; D007041:Hypoxanthine Phosphoribosyltransferase
keywords: Gout; Hyperuricemia; Hypoxanthine–guanine phosphoribosyltransferase deficiency; Lesch–Nyhan syndrome; Purine metabolism