Besouw Martine T P, Kleta Robert, Bockenhauer Detlef
Department of Pediatric Nephrology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Renal Unit, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
Pediatr Nephrol. 2020 Oct;35(10):1815-1824. doi: 10.1007/s00467-019-04371-y. Epub 2019 Oct 29.
Bartter and Gitelman syndromes are rare inherited tubulopathies characterized by hypokalaemic, hypochloraemic metabolic alkalosis. They are caused by mutations in at least 7 genes involved in the reabsorption of sodium in the thick ascending limb (TAL) of the loop of Henle and/or the distal convoluted tubule (DCT). Different subtypes can be distinguished and various classifications have been proposed based on clinical symptoms and/or the underlying genetic cause. Yet, the clinical phenotype can show remarkable variability, leading to potential divergences between classifications. These problems mostly relate to uncertainties over the role of the basolateral chloride exit channel CLCNKB, expressed in both TAL and DCT and to what degree the closely related paralogue CLCNKA can compensate for the loss of CLCNKB function. Here, we review what is known about the physiology of the transport proteins involved in these disorders. We also review the various proposed classifications and explain why a gene-based classification constitutes a pragmatic solution.
巴特综合征和吉特曼综合征是罕见的遗传性肾小管疾病，其特征为低钾血症、低氯血症性代谢性碱中毒。它们是由至少7个参与髓袢升支粗段（TAL）和/或远曲小管（DCT）钠重吸收的基因突变引起的。可以区分不同的亚型，并且基于临床症状和/或潜在的遗传原因提出了各种分类方法。然而，临床表型可能表现出显著的变异性，导致分类之间可能存在差异。这些问题主要与基底外侧氯流出通道CLCNKB的作用存在不确定性有关，CLCNKB在TAL和DCT中均有表达，以及与之密切相关的同源物CLCNKA能够在多大程度上补偿CLCNKB功能的丧失。在此，我们综述了关于这些疾病中涉及的转运蛋白生理学的已知信息。我们还综述了各种提出的分类方法，并指出基于基因的分类是一种实用的解决方案。
