Genetic background of uric acid metabolism in a patient with severe chronic tophaceous gout.
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.
Institute of Rheumatology, Prague, Czech Republic; Department of Rheumatology, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
Lenka
L
Petru
Institute of Rheumatology, Prague, Czech Republic; Department of Rheumatology, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
Katerina
K
Pavelcova
Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic; Institute of Inherited Metabolic Disorders, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic.
Ivan
I
Sebesta
Institute of Rheumatology, Prague, Czech Republic; Institute of Inherited Metabolic Disorders, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic. Electronic address: stiburkova@revma.cz.
Blanka
B
Stiburkova
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2 / Q000235:genetics; D002908:Chronic Disease; D000068617:Genetic Background; D006073:Gout / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics; D027361:Organic Anion Transporters / Q000235:genetics; D014527:Uric Acid / Q000378:metabolism*
C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D009363:Neoplasm Proteins; D027361:Organic Anion Transporters; C103862:urate transporter; D014527:Uric Acid; D007041:Hypoxanthine Phosphoribosyltransferase
ABCG2; Gout; Hyperuricemia; Hypoxanthine-guanine phosphoribosyltransferase deficiency; Tophi; Urate transporter