The molecular basis of inherited hypokalemic alkalosis: bartter's
and gitelman's syndromes.
Simon, David B., and Richard P. Lifton.
Howard Hughes Medical Institute, Departments of Medicine
(Nephrology) and Genetics, Boyer Center for Molecular Medicine, Yale
University School of Medicine, New Haven, Connecticut 06510
APStracts 3:0154F, 1996.
Hypokalemic alkalosis with low blood pressure can be caused by a
number of medications or alternatively as an autosomal recessive
genetic trait. Molecular genetic approaches to this problem have
recently demonstrated that mutations in genes encoding the thiazide
-sensitive Na - Cl cotransporter or the bumetanide-sensitive Na - K -
2Cl cotransporter produce two distinctive clinical and physiologic
pictures featuring hypokalemic alkalosis. Mutations in the latter
cause a phenotypic picture called Bartter's syndrome that includes
marked hypercalciuria, and neonatal presentation with marked
intravascular volume depletion. Mutations in the former cotransporter
result in Gitelman's syndrome, which includes hypocalciuria,
hypomagnesemia and typically older clinical presentation with
predominant muscular signs and symptoms. These findings establish the
molecular basis of these disorders, and indicate that the diverse
abnormalities seen in affected patients derive from primary defects
in these mediators of cotransport function. Moreover, These findings
have implications for normal mechanisms of renal electrolyte
homeostasis, and for potential phenotypic effects in the more common
heterozygous carriers of these mutations.
Received 19 July 1996; accepted in final form 28 August 1996.
APS Manuscript Number F207-6.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 19 September 1996