Müller T, Wijmenga C, Phillips A D, Janecke A, Houwen R H, Fischer H, Ellemunter H, Frühwirth M, Offner F, Hofer S, Müller W, Booth I W, Heinz-Erian P
Department of Pediatrics, University of Innsbruck, Innsbruck, Austria.
Gastroenterology. 2000 Dec;119(6):1506-13. doi: 10.1053/gast.2000.20514.
BACKGROUND & AIMS: Congenital sodium diarrhea (CSD) is caused by defective sodium/proton exchange with only 6 sporadic cases reported. The genetics of the disease have not been established. We studied 5 infants with secretory diarrhea, identified in a circumscribed rural area in Austria, to define the mode of transmission and the involvement of candidate genes known to encode for sodium/proton exchangers (NHEs).
We collected clinical and laboratory data from 5 affected patients, analyzed the pedigrees of their families, and performed homozygosity mapping and multipoint linkage analysis studies in 4 candidate regions known to contain NHE genes.
The diagnosis of CSD in 4 of 5 patients was based on daily fecal sodium excretion between 98 and 190 mmol/L, hyponatremia, metabolic acidosis, and low-to-normal urinary sodium concentrations. Pedigree analysis of the affected 2 CSD families revealed parental consanguinity and a common single ancestor 5 generations ago. Homozygosity mapping and/or multipoint linkage analysis excluded the NHE1 locus on chromosome 1, NHE2 locus on chromosome 2, NHE3 locus on chromosome 5, and NHE5 locus on chromosome 16 as potential candidate genes for CSD in this pedigree. Results on NHE4 were inconclusive because the precise chromosomal location of this NHE gene in humans is currently unknown.
Our data indicate that CSD is an autosomal recessive disorder but is not related to mutations in the NHE1, NHE2, NHE3, and NHE5 genes encoding for currently known sodium/proton exchangers.
先天性钠腹泻（CSD）由钠/质子交换缺陷引起，仅报告了6例散发病例。该疾病的遗传学尚未明确。我们研究了在奥地利一个特定农村地区发现的5例分泌性腹泻婴儿，以确定其传播方式以及已知编码钠/质子交换体（NHEs）的候选基因的参与情况。
我们收集了5例受影响患者的临床和实验室数据，分析了他们家族的谱系，并在已知包含NHE基因的4个候选区域进行了纯合性定位和多点连锁分析研究。
5例患者中有4例的CSD诊断基于每日粪便钠排泄量在98至190 mmol/L之间、低钠血症、代谢性酸中毒以及尿钠浓度低至正常。对2个受影响的CSD家族的谱系分析显示父母近亲结婚以及5代前有一个共同的单一祖先。纯合性定位和/或多点连锁分析排除了1号染色体上的NHE1位点、2号染色体上的NHE2位点、5号染色体上的NHE3位点和16号染色体上的NHE5位点作为该谱系中CSD的潜在候选基因。关于NHE4的结果尚无定论，因为该NHE基因在人类中的精确染色体位置目前尚不清楚。
我们的数据表明CSD是一种常染色体隐性疾病，但与目前已知的编码钠/质子交换体的NHE1、NHE2、NHE3和NHE5基因的突变无关。
