Infantile variant of Bartter syndrome and sensorineural deafness: A new autosomal recessive disorder

Landau, Daniel; Shalev, Hadar; Ohaly, Meli; Carmi, Rivka

doi:10.1002/ajmg.1320590411

Cited by 91 publications

(68 citation statements)

References 32 publications

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“…The coincidence of tubular disorder and hearing loss substantiates the previous hypothesis of a pleiotropic effect of a single gene defect. 18,19 Both tubular salt reabsorption and mechano-electrical transduction in the Corti organ rely on the electrochemical gradients across epithelial cell membranes, generated by solute transporters and ion channels. In the past, mutation in several of them were found to account for congenital salt-losing tubulopathies 2 or to cause nonsyndromic or syndromic hearing loss.…”

Section: Discussionmentioning

confidence: 99%

“…15 This might be related to a high incidence of sensorineural deafness (SND) in preterm infants (up to 10% 16,17 ), because HPS/aBS patients are born prematurely. However, Landau et al 18 described an association of "infantile Bartter syndrome" with SND in an inbred Bedouin kindred with at least 5 affected individuals. They proposed that this association may result from the pleiotropic effect of a sin-gle recessive gene defect.…”

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confidence: 99%

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Hypokalemic Salt-Losing Tubulopathy With Chronic Renal Failure and Sensorineural Deafness

Jeck

Reinalter

Henne³

et al. 2001

Pediatrics

109

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ABSTRACT.Objective. To characterize a rare inherited hypokalemic salt-losing tubulopathy with linkage to chromosome 1p31.Methods. We conducted a retrospective analysis of the clinical data for 7 patients in whom cosegregation of the disease with chromosome 1p31 had been demonstrated. In addition, in 1 kindred, prenatal diagnosis in the second child was established, allowing a prospective clinical evaluation.Results. Clinical presentation of the patients was homogeneous and included premature birth attributable to polyhydramnios, severe renal salt loss, normotensive hyperreninemia, hypokalemic alkalosis, and excessive hyperprostaglandin E-uria, which suggested the diagnosis of hyperprostaglandin E syndrome/antenatal Bartter syndrome. However, the response to indomethacin was only poor, accounting for a more severe variant of the disease. The patients invariably developed chronic renal failure. The majority had extreme growth retardation, and motor development was markedly delayed. In addition, all patients turned out to be deaf.Conclusion. The hypokalemic salt-losing tubulopathy with chronic renal failure and sensorineural deafness represents not only genetically but also clinically a disease entity distinct from hyperprostaglandin E syndrome/antenatal Bartter syndrome. A pleiotropic effect of a single gene defect is most likely causative for syndromic hearing loss. Pediatrics 2001;108(1). URL: http:// www.pediatrics.org/cgi/content/full/108/1/e5; tubulopathy, Bartter syndrome, polyhydramnios, renal failure, syndromic deafness, pleiotropic gene.ABBREVIATIONS. HPS/aBS, hyperprostaglandin E syndrome/ antenatal Bartter syndrome; TAL, thick ascending limb of Henle's loop; PGE 2 , prostaglandin E 2 ; NKCC2, furosemide-sensitive Na-K-2Cl cotransporter; ROMK, renal outer-medullary potassium channel; SND, sensorineural deafness; GFR, glomerular filtration rate; BERA, brainstem-evoked response audiometry; PPN, partial parenteral nutrition. I nherited salt-losing tubulopathies with hypokalemic alkalosis involve an overlapping set of renal tubular disorders that can be subdivided into at least 3 phenotypes: 1) classic Bartter syndrome, 2) Gitelman syndrome, and 3) hyperprostaglandin E syndrome/antenatal Bartter syndrome (HPS/aBS). 1,2 Whereas patients with classic Bartter syndrome and Gitelman syndrome typically present in early infancy and childhood or adolescence, manifestation of HPS/aBS occurs in utero and the neonatal course is severe. 3 The first clinical sign is maternal polyhydramnios caused by fetal polyuria, which regularly results in premature birth between 28 and 34 weeks of gestation. 4,5 Postnatally, affected infants present with the typical pattern of impaired tubular reabsorption in the thick ascending limb of Henle's loop (TAL), including salt wasting, isosthenuric or hyposthenuric polyuria, and hypercalciuria with subsequent medullary nephrocalcinosis. 6 -8 Characteristically, endogenous formation of prostaglandin E 2 (PGE 2 ) is stimulated markedly, resulting in additional aggravation of saluretic polyuri...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Hypokalemic Salt-Losing Tubulopathy With Chronic Renal Failure and Sensorineural Deafness

Jeck

Reinalter

Henne³

et al. 2001

Pediatrics

109

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“…On the basis of clinical presentation, additional symptoms, and the biochemical profile, especially with respect to calcium and magnesium handling, at least four different disease entities can be discerned (71,72). Over the last few years, this clinical differentiation has been substantiated by the characterization of the underlying molecular defects in five different genes in patients suffering from these diseases.…”

Section: Salt-losing Tubular Disordersmentioning

confidence: 99%

Recent Advances in Molecular Genetics of Hereditary Magnesium-Losing Disorders

Konrad¹,

Weber²

2003

Journal of the American Society of Nephrology

111

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Abstract. Recent advances in molecular genetics in hereditary hypomagnesemia substantiated the role of a variety of genes and their encoded proteins in human magnesium transport mechanisms. This knowledge on underlying genetic defects helps to distinguish different clinical subtypes and gives first insight into molecular components involved in magnesium transport. By mutation analysis and functional protein studies, novel pathophysiologic aspects were elucidated. For some of these disorders, transgenic animal models were generated to study genotype-phenotype relations and disease pathology. This review will discuss genetic and clinical aspects of familial disorders associated with magnesium wasting and focuses on the recent progress that has been made in molecular genetics. Besides isolated renal forms of hereditary hypomagnesemia, the following disorders will also be presented: familial hypomagnesemia with hypercalciuria and nephrocalcinosis, hypomagnesemia with secondary hypocalcemia, Ca 2ϩ /Mg 2ϩ -sensing receptor-associated disorders, and disorders associated with renal salt-wasting and hypokalemic metabolic alkalosis, comprising the Gitelman syndrome and the Bartter-like syndromes.

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“…2,3 Among them, Bartter syndrome type IV usually exhibits a severe phenotype. Fetal polyuria causes maternal polyhydramnios, 4,5 and, postnatally, salt wasting and polyuria occur as consequences of impaired tubular reabsorption. In some patients, renal failure occurs at a young age.…”

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confidence: 99%

“…In addition to the renal phenotype, patients experience sensorineural deafness. 4 The disease gene of Bartter type IV, BSND, encodes barttin, an accessory subunit of a subclass of ClC channels, the ClC-K channels. 6 -8 Barttin mutations impair chloride absorption in various sections of the nephron as well as potassium secretion in the stria vascularis and the vestibular labyrinth.…”

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confidence: 99%

Disease-Causing Dysfunctions of Barttin in Bartter Syndrome Type IV

Janssen

Scholl²,

Domeyer³

et al. 2009

Journal of the American Society of Nephrology

116

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Bartter syndrome type IV is an inherited human condition characterized by severe renal salt wasting and sensorineural deafness. The causal gene, BSND, encodes barttin, an accessory subunit of chloride channels located in the kidney and inner ear. Barttin modulates the stability, cell surface localization, and function of ClC-K channels; distinct mutations cause phenotypes of varying severity. For definition of the molecular basis of this diversity, the functional consequences of six disease-causing mutations (R8L, R8W, G10S, Q32X, G47R, and E88X) on ClC-K channel properties were studied by heterologous expression in renal cell lines, electrophysiology, confocal imaging, and biochemical analysis. Three missense mutations (R8L, R8W, and G10S) eliminated the function of ClC-K/barttin channels but did not prevent the insertion of the channels into the surface membrane. Another mutant that produces a mild renal phenotype (G47R) was capable of performing all functions of wild-type barttin but bound to ClC-K channels less effectively. The nonsense mutation E88X affected epithelial sorting, leading to equal amounts of barttin inserting into the basolateral and apical membranes, contrasting with the preferential apical insertion of wild-type barttin. Last, the nonsense mutation Q32X allowed barttin to associate with ClC-K channels but prevented surface membrane insertion and channel activation. These results demonstrate that Bartter syndrome type IV can be caused by various derangements in the function of barttin, likely contributing to the diversity of observed phenotypes.

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Infantile variant of Bartter syndrome and sensorineural deafness: A new autosomal recessive disorder

Cited by 91 publications

References 32 publications

Hypokalemic Salt-Losing Tubulopathy With Chronic Renal Failure and Sensorineural Deafness

Hypokalemic Salt-Losing Tubulopathy With Chronic Renal Failure and Sensorineural Deafness

Recent Advances in Molecular Genetics of Hereditary Magnesium-Losing Disorders

Disease-Causing Dysfunctions of Barttin in Bartter Syndrome Type IV

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