Pendred Syndrome

Pendred Syndrome is an autosomal recessive disorder caused by mutations in the solute carrier family 26 member 4 gene (SLC26A4) which has some relevance to nephrology and acid-base metabolism. Its main phenotypic manifestations are thyroid goiter and sensorineural deafness. Where does the nephrology come in? It does not appear that these individuals have acid-base problems at baseline, but there are reports of their developing a severe hypokalemic metabolic alkalosis when treated with thiazide diuretics. I'll explain.

The SLC26A4 gene product encodes an ion transporter which enables (1) iodine ion transport (hence the goiter) and (2) chloride-bicarbonate exchange. In the inner ear, impaired bicarbonate secretion leads to acidification of the endolymph and damage to the underlying hair cells, hence the deafness. In the kidney, the SLC26A4 gene product is expressed in beta-intercalated cells of the collecting duct. Recall that the collecting duct has two flavors of intercalated cells: the alpha-intercalated cells (which secrete protons) and the beta-intercalated cells (which secrete bicarbonate). A decreased ability to secrete bicarbonate, coupled with reduced NaCl reabsorption from thiazide diuretics, could therefore explain the metabolic alkalosis seen in Pendred Syndrome patients.

Have I ever seen a case? Not that I can think of, though I wouldn't necessarily know as I mentioned before that individuals don't typically get metabolic alkalosis unless treated with diuretic. It's uncommon but not that uncommon, as many sources cite Pendred Syndrome as accounting for up to 10% of heritable deafness.