Severe Gouty Arthritis and Mild Neurologic Symptoms Due to F199C, a Newly Identified Variant of the Hypoxanthine Guanine Phosphoribosyltransferase
Severe Gouty Arthritis and Mild Neurologic Symptoms Due to F199C, a Newly Identified Variant of the Hypoxanthine Guanine Phosphoribosyltransferase
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DOI：
10.1002/art.24617
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发表时间：
2009-07-01
影响因子：
--
通讯作者：
Ceballos-Picot, Irene
中科院分区：
文献类型：
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作者：
Ea, Hang-Korng;Bardin, Thomas;Ceballos-Picot, Irene
次黄嘌呤鸟嘌呤磷酸核糖转移酶（HPRT）活性的缺乏导致尿酸的过度产生。根据酶缺乏的程度，还可以观察到大量的神经系统特征，从轻度或无神经系统受累到完全的莱施尼汉病。在此，我们描述了一个高尿酸血症，青少年发病痛风性关节炎，肾结石，和轻度神经系统症状的患者，归因于一个新发现的hprt基因的变异，c.596T>G，导致氨基酸变化p.F199C。残余HPRT活性（8%）保护了该患者免于严重神经系统受累。突变蛋白的建模用于预测导致部分酶活性的机制。在青少年和中年痛风患者中，仔细的神经系统检查是必要的，以检测可能导致HPRT缺乏症诊断的轻微症状。
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.