Open AccessSevere gouty arthritis and mild neurologic symptoms due to F199C, a newly identified variant of the hypoxanthine guanine phosphoribosyltransferase
Author(s) -
Ea HangKorng,
Bardin Thomas,
Jinnah H. A.,
Aral Bernard,
Lioté Frédéric,
CeballosPicot Irène
Publication year - 2009
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.24617
Subject(s) - hypoxanthine guanine phosphoribosyltransferase , gout , phosphoribosyltransferase , hyperuricemia , lesch–nyhan syndrome , uric acid , medicine , gouty arthritis , arthritis , hypoxanthine phosphoribosyltransferase , hypoxanthine , gastroenterology , endocrinology , enzyme , biochemistry , biology , gene , mutant
A deficiency in hypoxanthine guanine phosphoribosyltransferase (HPRT) activity leads to overproduction of uric acid. According to the degree of enzymatic deficiency, a large spectrum of neurologic features can also be observed, ranging from mild or no neurologic involvement to complete Lesch‐Nyhan disease. Herein, we describe a patient with hyperuricemia, juvenile‐onset gouty arthritis, nephrolithiasis, and mild neurologic symptoms, attributed to a newly identified variant of the hprt gene, c.596T>G, resulting in the amino acid change p.F199C. Residual HPRT activity (8%) protected against severe neurologic involvement in this patient. Modeling of the mutated protein was used to predict the mechanisms that led to partial enzymatic activity. Careful neurologic examination is warranted in juvenile and middle‐aged patients with gout, in order to detect mild symptoms that may lead to a diagnosis of HPRT deficiency.