A NOVEL KCNJ5 GENE MUTATION ASSOCIATED WITH FAMILIAL ALDOSTERONISM TYPE III WITHOUT HYPERTENSION

Primary aldosteronism (PA) involves excessive autonomous aldosterone (ALD) secretion by the adrenal cortex, leading to water and sodium retention and renin-angiotensin system inhibition, causing hypertension and K+ imbalance. Familial hyperaldosteronism type III (FH-III) is a rare subtype, characterized by hypokalemia with hypertension and adrenal hyperplasia. Eight associated pathogenic potassium inward rectifying channel protein subfamily J member 5 (KCNJ5) mutations have been reported. This study reports a Chinese family with FH-III associated with a rare KCNJ5 variant (c.536A>G, p.Asn179Ser), which has been previously reported in cardiac genetics databases (rs147070381). Our study expands its phenotypic spectrum to include familial aldosteronism.

A middle-aged female presented with recurrent hypokalemia unresponsive to oral potassium supplementation. She and her family underwent comprehensive clinical examination, biochemical testing, imaging studies, and whole-exome sequencing.

She exhibited recurrent hypokalemia without hypertension, with fluctuating ALD, which were controlled with spironolactone. The proband, along with her sister and mother, were found to carry a heterozygous KCNJ5 variant (exon 2: c.536A>G, p.Asn179Ser).

FH-III symptoms vary widely, making diagnosis challenging in patients who solely present with recurrent hypokalemia. Early gene sequencing facilitates accurate diagnosis to guide appropriate treatment.