What are the causes of uric acid overproduction in hyperuricemia?

Updated: Nov 03, 2020
  • Author: James W Lohr, MD; Chief Editor: Vecihi Batuman, MD, FASN  more...
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Uric acid overproduction may be idiopathic. Known causes include the following:

  • Hypoxanthine guanine phosphoribosyltransferase (HGPRT) deficiency (Lesch-Nyhan syndrome): This is an inherited X-linked disorder. HGRPT catalyzes the conversion of hypoxanthine to inosinic acid, in which PRPP serves as the phosphate donor. The deficiency of HGPRT results in accumulation of 5-phospho-alpha-d-ribosyl pyrophosphate (PRPP), which accelerates purine biosynthesis with a resultant increase in uric acid production. In addition to gout and uric acid nephrolithiasis, these patients develop a neurologic disorder that is characterized by choreoathetosis, spasticity, growth, mental function retardation, and, occasionally, self-mutilation.

  • Partial deficiency of HGPRT (Kelley-Seegmiller syndrome): This is also an X-linked disorder. Patients typically develop gouty arthritis in the second or third decade of life, have a high incidence of uric acid nephrolithiasis, and may have mild neurologic deficits.

  • Increased activity of PRPP synthetase: This is a rare X-linked disorder in which patients make mutated PRPP synthetase enzymes with increased activity. These patients develop gout when aged 15-30 years and have a high incidence of uric acid kidney stones.

  • Diet: A diet rich in high-purine meats, organ foods, and legumes can result in an overproduction of uric acid.

  • Increased nucleic acid turnover: This may be observed in persons with hemolytic anemia and hematologic malignancies such as lymphoma, myeloma, or leukemia.

  • Tumor lysis syndrome: This may produce the most serious complications of hyperuricemia.

  • Glycogenoses III, V, and VII

  • Exposure to persistent organic pollutants (eg, organochlorine pesticides) [14]

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