Godefroid Nathalie, Riveira-Munoz Eva, Saint-Martin Christine, Nassogne Marie-Cécile, Dahan Karin, Devuyst Olivier
Department of Pediatrics, Division of Nephrology, Center for Human Genetics, Université catholique de Louvain Medical School, Saint-Luc Academic Hospital, Brussels, Belgium.
Am J Kidney Dis. 2006 Nov;48(5):e73-9. doi: 10.1053/j.ajkd.2006.08.005.
We report a case of Gitelman syndrome (GS) in a dizygotic twin who presented at 12 years of age with growth delay, metabolic alkalosis, hypomagnesemia and hypokalemia with inappropriate kaliuresis, and idiopathic intracranial hypertension with bilateral papilledema (pseudotumor cerebri). The patient, her twin sister, and her mother also presented with cerebral cavernous malformations. Based on the early onset and normocalciuria, Bartter syndrome was diagnosed first. However, mutation analysis showed that the proband is a compound heterozygote for 2 mutations in SLC12A3: a substitution of serine by leucine at amino acid position 555 (p.Ser555Leu) and a novel guanine to cytosine transition at the 5' splice site of intron 22 (c.2633+1G>C), providing the molecular diagnosis of GS. These mutations were not detected in 200 normal chromosomes and cosegregated within the family. Analysis of complementary DNA showed that the heterozygous nucleotide change c.2633+1G>C caused the appearance of 2 RNA molecules, 1 normal transcript and 1 skipping the entire exon 22 (r.2521_2634del). Supplementation with potassium and magnesium improved clinical symptoms and resulted in catch-up growth, but vision remained impaired. Three similar associations of Bartter syndrome/GS with pseudotumor cerebri were found in the literature, suggesting that electrolyte abnormalities and secondary aldosteronism may have a role in idiopathic intracranial hypertension. This study provides further evidence for the phenotypical heterogeneity of GS and its association with severe manifestations in children. It also shows the independent segregation of familial cavernomatosis and GS.
我们报告了一例双卵双胞胎中的吉特曼综合征（GS）病例，该患者12岁时出现生长发育迟缓、代谢性碱中毒、低镁血症、低钾血症伴不适当的尿钾增多，以及伴有双侧视乳头水肿的特发性颅内高压（假性脑瘤）。该患者、她的双胞胎姐妹以及她的母亲还患有脑海绵状畸形。基于起病早和正常尿钙，最初诊断为巴特综合征。然而，突变分析显示先证者是SLC12A3基因2个突变的复合杂合子：第555位氨基酸丝氨酸被亮氨酸替代（p.Ser555Leu），以及内含子22的5'剪接位点处新出现的鸟嘌呤到胞嘧啶的转换（c.2633 + 1G>C），从而作出了GS的分子诊断。这些突变在200条正常染色体中未检测到，且在家族中呈共分离。互补DNA分析显示，杂合核苷酸变化c.2633 + 1G>C导致出现2种RNA分子，1种正常转录本和1种跳过整个外显子22的转录本（r.2521_2634del）。补充钾和镁改善了临床症状并实现了追赶生长，但视力仍受损。文献中发现了3例巴特综合征/GS与假性脑瘤的类似关联，提示电解质异常和继发性醛固酮增多症可能在特发性颅内高压中起作用。本研究为GS的表型异质性及其与儿童严重表现的关联提供了进一步证据。它还显示了家族性海绵状血管瘤病和GS各自独立分离。
