Genetic background of uric acid metabolism in a patient with severe chronic tophaceous gout

Clin Chim Acta. 2016 Sep 1:460:46-9. doi: 10.1016/j.cca.2016.06.007. Epub 2016 Jun 9.

Abstract

Hyperuricemia depends on the balance of endogenous production and renal excretion of uric acid. Transporters for urate are located in the proximal tubule where uric acid is secreted and extensively reabsorbed: secretion is principally ensured by the highly variable ABCG2 gene. Enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT) plays a central role in purine metabolism and its deficiency is an X-linked inherited metabolic disorder associated with clinical manifestations of purine overproduction. Here we report the case of a middle-aged man with severe chronic tophaceous gout with a poor response to allopurinol and requiring repeated surgical intervention. We identified the causal mutations in the HPRT1 gene, variant c.481G>T (p.A161S), and in the crucial urate transporter ABCG2, a heterozygous variant c.421C>A (p.Q141K). This case shows the value of an analysis of the genetic background of serum uric acid.

Keywords: ABCG2; Gout; Hyperuricemia; Hypoxanthine-guanine phosphoribosyltransferase deficiency; Tophi; Urate transporter.

Publication types

  • Case Reports

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2 / genetics
  • Chronic Disease
  • Genetic Background*
  • Gout / genetics*
  • Gout / metabolism
  • Humans
  • Hypoxanthine Phosphoribosyltransferase / deficiency
  • Hypoxanthine Phosphoribosyltransferase / genetics
  • Hypoxanthine Phosphoribosyltransferase / metabolism
  • Male
  • Middle Aged
  • Mutation
  • Neoplasm Proteins / genetics
  • Organic Anion Transporters / genetics
  • Uric Acid / metabolism*

Substances

  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • Neoplasm Proteins
  • Organic Anion Transporters
  • urate transporter
  • Uric Acid
  • Hypoxanthine Phosphoribosyltransferase

Supplementary concepts

  • Gout, HPRT-Related