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

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.