Recurrent exercise-induced acute renal failure in a young Pakistani man with severe renal hypouricemia and SLC2A9 compound heterozygosity.
Recurrent exercise-induced acute renal failure in a young Pakistani man with severe renal hypouricemia and SLC2A9 compound heterozygosity.
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重复运动引起的运动引起的急性肾衰竭，患有严重的肾脏低血症和SLC2A9复合杂合性的年轻男子。
DOI：
10.1186/1471-2350-15-3
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发表时间：
2014-01-07
影响因子：
--
通讯作者：
Cancarini G
中科院分区：
文献类型：
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作者：
Jeannin G;Chiarelli N;Gaggiotti M;Ritelli M;Maiorca P;Quinzani S;Verzeletti F;Possenti S;Colombi M;Cancarini G
家族性肾性低尿酸血症（RHUC）是一种以低尿酸血症、高肾尿酸排泄分数（FE-UA）为特征的遗传性疾病，可并发急性肾功能衰竭和肾结石。 SLC22A12 基因的功能丧失突变导致 1 型肾性低尿酸血症 (RHUC1)，而 2 型肾性低尿酸血症 (RHUC2) 则由 SLC2A9 基因突变引起。我们描述了一名 24 岁巴基斯坦男子，他因严重运动性急性肾衰竭 (EIARF)、腹痛和发烧两次入院；他的血清 UA 水平非常低（第一次 0.2 mg/dl，第二次 0.09 mg/dl）和高 FE-UA（分别为 200% 和 732%），提示 RHUC。对两种尿酸转运蛋白的突变分析揭示了 SLC2A9 基因中两个不同错义突变的新复合杂合性：p.Arg380Trp（已在杂合性中鉴定）和 p.Gly216Arg（先前在一些 RHUC2 患者中发现纯合性或复合杂合性）。与之前报道的携带这些突变的患者相比，我们的先证者表现出最高的 FE-UA 水平，表明 p.Arg380Trp 和 p.Gly216Arg 突变的组合最严重地影响 UA 的肾脏处理。该患者的临床和分子发现以及文献综述为该疾病的基因型-表型相关性提供了新的见解，支持 RHUC2 常染色体隐性遗传模式的证据。需要对 GLUT9、URAT1 和其他尿酸盐转运蛋白的功能特性进行进一步研究，以评估其潜在的研究和临床意义。
Familial renal hypouricemia (RHUC) is a hereditary disease characterized by hypouricemia, high renal fractional excretion of uric acid (FE-UA) and can be complicated by acute kidney failure and nephrolithiasis. Loss-of-function mutations in the SLC22A12 gene cause renal hypouricemia type 1 (RHUC1), whereas renal hypouricemia type 2 (RHUC2) is caused by mutations in the SLC2A9 gene. We describe a 24-year-old Pakistani man who was admitted twice to our hospital for severe exercise-induced acute renal failure (EIARF), abdominal pain and fever; he had very low serum UA levels (0.2 mg/dl the first time and 0.09 mg/dl the second time) and high FE-UA (200% and 732% respectively), suggestive of RHUC. Mutational analyses of both urate transporters revealed a new compound heterozygosity for two distinct missense mutations in the SLC2A9 gene: p.Arg380Trp, already identified in heterozygosity, and p.Gly216Arg, previously found in homozygosity or compound heterozygosity in some RHUC2 patients. Compared with previously reported patients harbouring these mutations, our proband showed the highest FE-UA levels, suggesting that the combination of p.Arg380Trp and p.Gly216Arg mutations most severely affects the renal handling of UA. The clinical and molecular findings from this patient and a review of the literature provide new insights into the genotype-phenotype correlation of this disorder, supporting the evidence of an autosomal recessive inheritance pattern for RHUC2. Further investigations into the functional properties of GLUT9, URAT1 and other urate transporters are required to assess their potential research and clinical implications.