Recurrent EIARF and PRES With Severe Renal Hypouricemia by Compound Heterozygous SLC2A9 Mutation
Recurrent EIARF and PRES With Severe Renal Hypouricemia by Compound Heterozygous SLC2A9 Mutation
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DOI：
10.1542/peds.2010-2592
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发表时间：
2011-06-01
期刊：
影响因子：
8
通讯作者：
Yoshikawa, Norishige
中科院分区：
文献类型：
--
作者：
Shima, Yuko;Nozu, Kandai;Yoshikawa, Norishige
肾性低尿酸血症（RHU）是一种遗传性疾病，易使受影响的人发生运动诱发的急性肾功能衰竭（EIARF）。在大多数RHU患者中，这种疾病是由SLC 22 A12（溶质载体家族22，成员12）的功能缺失突变引起的，该突变编码尿酸盐转运蛋白1（URAT 1）。最近发现URAT 1基因无任何突变的RHU患者在葡萄糖转运蛋白9（GLUT 9）基因（SLC 2A 9 [溶质载体家族2，成员9]）中存在突变。在具有SLC 22 A12突变的RHU患者中，中枢神经系统并发症似乎很少见。在这里，我们报告的情况下，一个女孩与严重的RHU（血清尿酸盐：5.9 μ mol/L [0.1 mg/dL]）与复发性EIARF相关，其中疾病是由SLC 2A 9复合杂合突变（父亲等位基因的无义突变）引起的通过逆转录聚合酶链反应（PCR）、半定量PCR、长链PCR和直接测序检测到在母亲等位基因中存在一个大的重复（c.1-2981_1204 + 16502）。EIARF的发作并发可逆性后部脑病综合征（PRES），这表明PRES与GLUT 9或严重低尿酸血症有关。这是第二次报告的突变的两个等位基因的SLC 2A 9，导致严重的低尿酸血症。我们的研究结果表明，即使是SLC 2A 9杂合状态的无义突变也不会导致严重的低尿酸血症，并且支持了先前的推测，即两个SLC 2A 9等位基因的突变都会导致严重的低尿酸血症。我们的病例表明，GLUT 9与URAT 1不同，可能在运动诱导的PRES中发挥特定作用。儿科2011; 127：e1621-e1625
Renal hypouricemia (RHU) is a hereditary disease that predisposes affected people to exercise-induced acute renal failure (EIARF). In most patients with RHU, the disorder is caused by loss-of-function mutations in SLC22A12 (solute carrier family 22, member 12), which encodes urate transporter 1 (URAT1). Patients with RHU without any mutations in the URAT1 gene were recently found to have a mutation in the glucose transporter 9 (GLUT9) gene (SLC2A9 [solute carrier family 2, member 9]). Central nervous system complications seem to be rare in patients with RHU with SLC22A12 mutations. Here, we report the case of a girl with severe RHU (serum urate: 5.9 mu mol/L [0.1 mg/dL]) associated with recurrent EIARF in whom the disease was caused by a compound heterozygous mutation in SLC2A9, a nonsense mutation in the paternal allele (p.G207X in exon 7), and a large duplication (c.1-2981_1204 + 16502) in the maternal allele detected by reverse-transcription polymerase chain reaction (PCR), semiquantitative PCR, long PCR, and direct sequencing. The episodes of EIARF were complicated by posterior reversible encephalopathy syndrome (PRES), which suggested a relationship between PRES and GLUT9 or severe hypouricemia. This is the second report of mutations of both alleles of SLC2A9 that resulted in severe hypouricemia. Our findings indicate that even a nonsense mutation responsible for the heterozygous status of SLC2A9 did not cause severe hypouricemia, and they lend support to previous speculation that mutations of both SLC2A9 alleles cause severe hypouricemia. Our case shows that GLUT9, unlike URAT1, may play a specific role in exercise-induced PRES. Pediatrics 2011; 127:e1621-e1625