Gout or Kelley-Seegmiller Syndrome


Gout, or Kelley-Seegmiller syndrome, is caused by a partial defect in the HPRT1 gene which codes for hypoxanthine-guanine phosphoribosyltransferase. Hypoxanthine-guanine phosphoribosyltransferase is an enzyme in purine metabolism. Its primarily functions to salvage purines from degraded DNA to renewed purine synthesis. In this role, it acts as a catalyst in the reaction between guanine and phosphoribosyl pyrophosphate (PRPP) to form GMP. A partial deficiency in this enzyme causes overproduction of uric acid, therefore it results in accumulation of uric acid in serum and increase urinary excretion of uric acid. Symptoms and signs include excruciating, sudden, unexpected, burning pain, as well as swelling, redness, warmth, and stiffness in the affected joint, usually in the great toe, tophi in the helix or antihelix of the ear, along the ulnar surface of the forearm, in the olecranon bursa, or in other tissues. Treatment has three objectives: manage symptoms of acute attacks, prevent acute attacks, and reduce serum uric acid.

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References

  1. OMIM: Entry 300323
  2. Zoref-Shani E, Feinstein S, Frishberg Y, Bromberg Y, Sperling O: Kelley-Seegmiller syndrome due to a unique variant of hypoxanthine-guanine phosphoribosyltransferase: reduced affinity for 5-phosphoribosyl-1-pyrophosphate manifested only at low, physiological substrate concentrations. Biochim Biophys Acta. 2000 Feb 21;1500(2):197-203. Pubmed
  3. Kelley WN, Rosenbloom FM, Henderson JF, Seegmiller JE: A specific enzyme defect in gout associated with overproduction of uric acid. Proc Natl Acad Sci U S A. 1967 Jun;57(6):1735-9. Pubmed