Gregoric Alojz, Rabelink Gwenda M, Kokalj Vokac Nadja, Varda Natasa Marcun, Zagradisnik Boris
Department of Pediatrics, Maribor Teaching Hospital, Ljubljanska 5, 2000 Maribor, Slovenia.
Pediatr Nephrol. 2005 Sep;20(9):1346-8. doi: 10.1007/s00467-005-1935-4. Epub 2005 Jun 18.
Hypoxanthine phosphoribosyltransferase (HPRT) deficiency is an inherited disorder. Complete deficiency of HPRT activity is phenotypically expressed as the devastating Lesch-Nyhan syndrome. Partial HPRT deficiency usually causes hyperuricemia, precocious gout, and uric acid nephrolithiasis. We describe an 18-year follow-up of a 5-year old boy with partial HPRT deficiency and report a novel mutation in his HPRT gene. He presented with overproduction of uric acid and passage of uric acid renal stones, and without gout or neurological and behavioral abnormalities. Treatment with allopurinol, adequate hydration, urinary alkalization, and a low-purine diet was started. No subsequent nephrolithiasis has occurred. After 18-year of this therapy his physical and neuropsychological status were normal, merely his glomerular filtration rate (GFR, normal 97-137 mL min(-1)/1.73 m(2)) fell from normal to 65.1 mL min(-1). The most likely cause of initial renal impairment in our patient is uric and/or xanthine crystalluria. A missense and transition mutation 169A>G (57ATG>GTG, 57met>val) in exon 3 of the patient's HPRT gene was identified and the mother was the carrier of the mutation. As far as we are aware, the identified mutation has not previously been reported. We named the mutant HPRT Maribor.
次黄嘌呤磷酸核糖转移酶(HPRT)缺乏症是一种遗传性疾病。HPRT活性完全缺乏在表型上表现为严重的莱施-奈恩综合征。HPRT部分缺乏通常会导致高尿酸血症、早熟性痛风和尿酸肾结石。我们描述了一名5岁HPRT部分缺乏男孩的18年随访情况,并报告了其HPRT基因中的一个新突变。他表现为尿酸生成过多和尿酸肾结石排出,无痛风或神经及行为异常。开始使用别嘌醇、充足补液、尿液碱化和低嘌呤饮食进行治疗。此后未再发生肾结石。经过18年的这种治疗,他的身体和神经心理状况正常,只是他的肾小球滤过率(GFR,正常为97 - 137 mL·min⁻¹/1.73 m²)从正常降至65.1 mL·min⁻¹。我们患者最初肾功能损害最可能的原因是尿酸和/或黄嘌呤结晶尿。在患者HPRT基因第3外显子中鉴定出一个错义转换突变169A>G(57ATG>GTG,57met>val),其母亲是该突变的携带者。据我们所知,并未能发现之前有过该突变的报道。我们将该突变的HPRT命名为马里博尔。