TY - JOUR T1 - New Mutation Affecting Hypoxanthine Phosphoribosyltransferase Responsible for Severe Tophaceous Gout JF - The Journal of Rheumatology JO - J Rheumatol SP - 1252 LP - 1254 DO - 10.3899/jrheum.131168 VL - 41 IS - 6 AU - CLÉMENT LAHAYE AU - FRANCK AUGÉ AU - MARTIN SOUBRIER AU - IRÈNE CEBALLOS-PICOT Y1 - 2014/06/01 UR - http://www.jrheum.org/content/41/6/1252.2.abstract N2 - To the Editor:Hypoxanthine phosphoribosyltransferase (HPRT) deficiency, which is due to mutations of the HPRT1 gene, is a rare cause of inherited hyperuricemia and gouty arthritis1. Different HPRT1 mutations induce various levels of residual HPRT enzymatic activity, resulting in clinical symptoms of various severity2. Complete HPRT deficiency leads to the classic clinical phenotype of Lesch-Nyhan disease (LND), characterized by uric acid overproduction and its sequelae (nephrolithiasis, gout, and tophi), motor dysfunction, and behavioral problems including recurrent self-injury3. However, there also are attenuated clinical variants in which some of these clinical features are either absent or clinically insignificant. Collectively, patients with attenuated phenotypes are designated Lesch-Nyhan variants (LNV)4. The mildest form of LNV includes only overproduction of uric acid and its associated problems. These patients do not have clinically overt neurological or behavioral abnormalities, and most often are described as having HPRT-related hyperuricemia (HRH). Between the 2 extreme phenotypes of LND and HRH is a spectrum of phenotypes with varying degrees of neurological abnormalities, designated HPRT-related neurological dysfunction (HRND). Patients with HRND have an overproduction of uric acid along with some neurological difficulties, but they do not exhibit the self-injurious behaviors seen in classic LND. Patients with LND or LNV have both increased monosodium urate monohydrate (MSU) crystal formation that leads to gouty arthritis and arthropathy, tophi, and/or nephrolithiasis4,5,6. The gout resulting from HPRT deficiency is remarkable in its severity and its propensity to form tophi5,6. Its juvenile onset in a male is an important diagnostic clue for HPRT deficiency. The discovery of more than 600 mutations in the HPRT1 gene and their … Address correspondence to Dr. I. Ceballos-Picot, Laboratoire de Biochimie métabolique, Hôpital Necker-Enfants malades, 149 rue de Sèvres, 75015 Paris, France. E-mail: irene.ceballos{at}nck.aphp.fr ER -