Hypokalemia and deafness

I attended a research seminar last week given by the discoverer of EAST syndrome. This a rare, autosomal recessive condition in which children present with Epilepsy, Ataxia, Sensorineural deafness and Tubulopathy. It was a fascinating lecture detailing the slow but painstaking process whereby they first realized that this was a unique condition and slowly, over time, discovered the cause. It is due to a defect in KCNJ10, a potassium channel expressed on the TAL, distal tubule and early collecting duct. It is thought that it allows potassium to escape the cell and hence is required for the proper function of the Na/K-ATPase. Affected patients present with hypokalemic metabolic alkalosis and salt-wasting. It is also expressed in the inner ear and the brain, particularly in the cerebellum, thus explaining the ataxia.

This made be wonder; how many other conditions exist where hypokalemia is associated with sensorineural deafness?

Antenatal Bartter syndrome with sensorineural deafness: This disease is due to a mutation in the gene BSND, which encodes for Barttin. Barttin is the beta subunit of the chloride channels ClCKA and ClCKB, expressed in the distal nephron and the inner ear. Affected children present with polyhydramnios, premature birth and severe neonatal salt-wasting. The deafness is progressive and irreversible. Unlike other forms of antenatal Bartter syndrome, it is not associated with nephrocalcinosis and does not respond to indomethacin. Although it often progresses to renal failure, this is not inevitable and milder phenotypes have been described.

Distal Renal Tubular Acidosis and Sensorineural Deafness: First described in 1966, this is an autosomal recessive disease caused by a mutation in the gene ATP6B1 leading to a defect in the H-ATPase. It is primarily expressed in the distal nephron but is also required for the maintenance of proper endolymph pH in the inner ear. Patients present with type 1 RTA, nephrocalcinosis, poor growth and irreversible sensorineural deafness.

Pendred Syndrome: This disease is thought to cause 10% of congenital deafness and was detailed in a previous post by Nate. It is due to a defect in HCO3-Cl exchange in the collecting duct. Affected patients are not usually hypokalemic under normal circumstances. However, they develop a hypokalemic metabolic alkalosis on treatment with thiazide diuretics, which is reversible on stopping the drug.

Mitochondrial Cytopathies: Sensorineural Deafness is a common problem in patients with mitochondrial disease and about 5% of patients have renal involvement; most commonly represented by the fanconi syndrome with RTA, hypokalemia, glucosuria and aminoaciduria presenting prior to 2 years of age. They can also be associated with glomerular disease and could be confused initially with Alport’s syndrome although hematuria is usually absent in these patients.

Honorable mention must go to loop diuretics, which along with causing hypokalemia, can lead to ototoxicity, particularly when used in high doses. They cause edema of the epithelium of the stria vascularis by changing ionic gradients between the perilymph and endolymph and the resulting hearing loss can be permanent.

Finally, there is a single case report from Japan of a patient who developed permanent unilateral sensorineural deafness following an episode of hypokalemic periodic paralysis. His potassium on presentation was 1.5 mmol/L and the deafness was thought to be due to an electrolyte imbalance in his inner ear.