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01-11-2012 | Original Article

SeSAME/EAST syndrome—phenotypic variability and delayed activity of the distal convoluted tubule

Authors: Ute I. Scholl, Haatal B. Dave, Ming Lu, Anita Farhi, Carol Nelson-Williams, James A. Listman, Richard P. Lifton

Published in: Pediatric Nephrology | Issue 11/2012

Abstract

Background

Mutations in the K⁺ channel KCNJ10 (Kir4.1) cause an autosomal recessive syndrome featuring seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalance (SeSAME). Kir4.1 localizes to the basolateral membrane of the renal distal convoluted tubule, and its loss of function mimics renal features of Gitelman syndrome, with hypokalemic alkalosis, hypomagnesemia, and hypocalciuria. Presentation early in life due to seizures provides an opportunity to investigate the development of the electrolyte defect with age.

Methods

We used DNA sequencing, electrophysiology, confocal imaging, and biochemistry to identify a new KCNJ10 mutation in a previously unreported family and determine its impact on channel function. We examined medical records to follow the development of electrolyte disorders with age.

Results

The four affected members were all homozygous for a novel T57I mutation that confers biochemical loss-of-function. Electrolytes in affected children were normal in the first years of life but showed significant worsening with age, resulting in clinically significant defects at age 5–8 years. Similar findings were seen in other SeSAME patients.

Conclusions

These findings provide evidence for a delayed activity of salt reabsorption by the distal convoluted tubule and suggest an explanation for the delayed clinical presentation of subjects with Gitelman syndrome.

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Title: SeSAME/EAST syndrome—phenotypic variability and delayed activity of the distal convoluted tubule
Authors: Ute I. Scholl
Haatal B. Dave
Ming Lu
Anita Farhi
Carol Nelson-Williams
James A. Listman
Richard P. Lifton
Publication date: 01-11-2012
Publisher: Springer-Verlag
Published in: Pediatric Nephrology / Issue 11/2012
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-012-2219-4

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

SeSAME/EAST syndrome—phenotypic variability and delayed activity of the distal convoluted tubule

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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