Bartter and Gitelman syndromes: Questions of class

Abstract

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.

Seudohipoparatiroidismo asociado con síndrome de Gitelman. Reporte de un caso

“…Lo anterior fue compatible con el síndrome de Gitelman, patología en la cual existe una alteración de la reabsorción de sodio en el túbulo contorneado distal, por mutación del cotransportador sodio-cloro, lo que conlleva al desarrollo de hiperaldosteronismo secundario. (13). En este síndrome los pacientes por lo general debutan durante la adolescencia con alcalosis metabólica hipocaliémica con presión arterial normal, a pesar del hiperaldosteronismo, como fue el caso del paciente en mención; asociado a esto, los pacientes típicamente cursan con hipocalciuria e hipomagnesemia, en contraste con el síndrome de Bartter donde la hipercalciuria es la característica distintiva (14).…”

Urinary Extracellular Vesicles and Salt-Losing Tubulopathies: A Proteomic Approach

“…There is still much to learn about proteins that are involved in the expression and activity of the mutated transporters. Since there is still a subgroup of patients in whom no mutation can be found in the genes that are currently known to cause SLT, a deeper investigation of uEV proteome in these syndromes could lead to the discovery of dysregulated species and it could possibly generate targets for future treatments [2,6].…”

“…Gitelman syndrome (GS) and Bartter syndrome (BS) are rare inherited salt-losing tubulopathies (SLT) characterized by hypokalaemic, hypochloraemic metabolic alkalosis [1,2]. They are marked by lower sodium chloride reabsorption of the distal nephron, which results in extracellular volume contraction and increased activity of the renin angiotensin aldosterone system [3].…”

“…They are marked by lower sodium chloride reabsorption of the distal nephron, which results in extracellular volume contraction and increased activity of the renin angiotensin aldosterone system [3]. They are caused by mutations in at least seven genes, involved in sodium/fluid reabsorption, in the thick ascending limb of the loop of Henle and/or the distal convoluted tubule [2,4]. Different classifications have been proposed based on clinical symptoms and/or on the underlying genetic cause.…”

Why is SARS-CoV-2 infection milder among children?

“…Finally, a recently released news report of a fatal case of COVID-19 in a 3-month-old infant with Bartter's syndrome has indicated that ACE2 does have a significant role in COVID-19. This is an interesting example of how rare genetic disorders may contribute to understanding the pathophysiology of common diseases: patients affected with this autosomal recessive tubulopathy have increased ACE2 levels and elevated renin and aldosterone levels (30). However, how these factors actually interact in the case of a SARS-CoV-2 infection remains to be determined.…”