Rare Genetic Disease Lends Insights into Renal Salt Handling

Studies of a rare mutation of the potassium-channel gene KCNJ10 suggest that this gene may play an important role in renal salt handling and blood pressure regulation, according to a study in The New England Journal of Medicine.

The report describes five children from two consanguineous families with a syndrome of epilepsy, ataxia, sensor neural deafness, and tubulopathy, which the authors designate “EAST syndrome.” The salt-losing tubulopathy was associated with a hypokalemic metabolic alkalosis, without high blood pressure. Genetic studies traced the autosomal recessive disorder to two mutations of KCNJ10, which encodes a potassium channel expressed in the brain, inner ear, and kidney.

Further studies linked the mutations to significant and specific reductions in potassium currents. In mice with deletions of the gene Kcnj10, dehydration and renal salt wasting were observed.

Studies of rare inherited renal tubular diseases have provided new insights into renal salt and water handling, with implications for the management of hypertension. The new findings suggest that KCNJ10 could play a key role in renal salt handling, and thus in maintenance and regulation of blood pressure. The authors suggest re-evaluating data from genomewide association studies to examine this possibility [Bockenhauer D, Feather S, Stanescu HC, Bandulik S, et al.: Epilepsy, ataxia, sensorineural deafness, tubulopathy, and KCNJ10 mutations. N Engl J Med 2009; 360:1960–1970].