Martin Kömhoff1, Kamel Laghmani. 1. aUniversitätskinderklinik Marburg, Philipps University, Marburg, Germany bCentre de Recherche des Cordeliers; INSERM, U. 1138; CNRS, ERL8228; Université Pierre et Marie Curie and Université Paris-Descartes, Paris, France.
Abstract
PURPOSE OF REVIEW: Antenatal Bartter syndrome (aBS) is a heterogenous disease resulting from defective ion transport in the thick ascending limb of the loop of Henle. Novel insights into the pathophysiology, as well as the recent identification of a novel genetic cause of aBS, merit an update on this topic. RECENT FINDINGS: In aBS, severe salt losing is further aggravated by defective salt sensing in the macula densa, where a reduced tubular salt concentration is perceived and glomerular filtration is increased instead of decreased. As patients with aBS come of age, there is an increased incidence of proteinuria and impaired renal function.Moreover, we recently reported a new form of aBS. Indeed, we described a series of nine families in whom pregnancies with male fetuses where complicated by acute polyhydramnios, preterm delivery and with severe but transient polyuria. We identified mutations in melanoma-associated antigen D2 in all study participants and showed, in vivo and in vitro, reduced expression of the furosemide and thiazide sensitive transporters sodium-potassium-2-chloride cotransporter and sodium chloride cotransporter, respectively. SUMMARY: Genetic studies revealed the complexity of ion transport in the thick ascending limb of the loop of Henle and will help to clarify the pathophysiology, which is essential to design new therapies.
PURPOSE OF REVIEW: Antenatal Bartter syndrome (aBS) is a heterogenous disease resulting from defective ion transport in the thick ascending limb of the loop of Henle. Novel insights into the pathophysiology, as well as the recent identification of a novel genetic cause of aBS, merit an update on this topic. RECENT FINDINGS: In aBS, severe salt losing is further aggravated by defective salt sensing in the macula densa, where a reduced tubular salt concentration is perceived and glomerular filtration is increased instead of decreased. As patients with aBS come of age, there is an increased incidence of proteinuria and impaired renal function.Moreover, we recently reported a new form of aBS. Indeed, we described a series of nine families in whom pregnancies with male fetuses where complicated by acute polyhydramnios, preterm delivery and with severe but transient polyuria. We identified mutations in melanoma-associated antigen D2 in all study participants and showed, in vivo and in vitro, reduced expression of the furosemide and thiazide sensitive transporters sodium-potassium-2-chloride cotransporter and sodium chloride cotransporter, respectively. SUMMARY: Genetic studies revealed the complexity of ion transport in the thick ascending limb of the loop of Henle and will help to clarify the pathophysiology, which is essential to design new therapies.
Authors: Paula Giménez-Mascarell; Carlotta Else Schirrmacher; Luis Alfonso Martínez-Cruz; Dominik Müller Journal: Front Pediatr Date: 2018-04-09 Impact factor: 3.418