Phenotypic variability in Bartter syndrome type I
Phenotypic variability in Bartter syndrome type I
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DOI：
10.1007/pl00013418
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发表时间：
2000-09-01
影响因子：
3
通讯作者：
Casari, G
中科院分区：
文献类型：
--
作者：
Bettinelli, A;Ciarmatori, S;Casari, G
据报道，患有 Na-K-2Cl 协同转运蛋白基因 (BSC) 突变的 I 型 Bartter 综合征患者的表型变异有限。这种遗传性肾小管疾病的诊断通常在产前至新生儿时期进行，因为存在羊水过多、早产、低钾血症、代谢性碱中毒、高钙尿症和肾钙质沉着症。在 9 名患有高钙尿症和肾钙质沉着症的儿童中，我们在 5 名儿童中发现了与 BSC 基因突变等位基因功能丧失一致的新突变。 5 例 BSC 基因突变病例中有 3 例异常，因为出生后最初几年没有出现低钾血症和代谢性碱中毒。在分子评估之前考虑不完全性远端肾小管酸中毒的诊断。另外三名患者患有低钾血症和高钙尿症。但在前两种情况下没有肾钙质沉着症，在第三种情况下有代谢性酸中毒而不是碱中毒。两名患者的 BSC 基因中显示出与前一组患者相同的错义突变 A555T，这表明他们有一个共同的祖先。第三名患者出现严重高钠血症和高氯血症约2个月，并假设诊断为肾性尿崩症，直至通过分子评估确诊为巴特综合征I型。我们的结论是，在一些 I 型 Bartter 综合征患者中，出生后最初几年可能不存在低钾血症和/或代谢性碱中毒，也可能存在持续性代谢性酸中毒或高钠血症和高氯血症。分子评估绝对可以对这种复杂的遗传性肾小管疾病的非典型病例进行诊断，根据我们的经验，这种疾病可能表现出表型变异。
Limited phenotypic variability has been reported in patients with Bartter syndrome type I, with mutations in the Na-K-2Cl cotransporter gene (BSC). The diagnosis of this hereditary renal tubular disorder is usually made in the antenatal-neonatal period, due to the presence of polyhydramnios, premature delivery, hypokalemia, metabolic alkalosis, hypercalciuria, and nephrocalcinosis. Among nine children with hypercalciuria and nephrocalcinosis, we identified new mutations consistent with a loss of function of the mutant allele of the BSC gene in five. Three of the five cases with BSC gene mutations were unusual due to the absence of hypokalemia and metabolic alkalosis in the first years of life. The diagnosis of incomplete distal renal tubular acidosis was considered before molecular evaluation. Three additional patients with hypokalemia and hypercalciuria. but without nephrocalcinosis in the first two and with metabolic acidosis instead of alkalosis in the third, were studied. Two demonstrated the same missense mutation A555T in the BSC gene as one patient of the previous group, suggesting a single common ancestor. The third patient presented with severe hypernatremia and hyperchloremia for about 2 months, and a diagnosis of nephrogenic diabetes insipidus was hypothesized until the diagnosis of Bartter syndrome type I was established by molecular evaluation. We conclude that in some patients with Bartter syndrome type I, hypokalemia and/or metabolic alkalosis may be absent in the first years of life and persistent metabolic acidosis or hypernatremia and hyperchloremia may also be present. Molecular evaluation can definitely establish the diagnosis of atypical cases of this complex hereditary tubular disorder, which, in our experience, may exhibit phenotypic variability.