[Analysis of a family with familial hyperaldosteronism type Ⅳ due to a mutation in the CACNA1H gene].

Abstract

This study reports on a family with familial hyperaldosteronism type Ⅳ caused by a mutation in the CACNA1H gene. The proband (male, 39 years) presented to the Inner Mongolia Medical University Affiliated Hospital on March 8, 2024, with a 25-year history of episodic weakness and a 5-year history of elevated blood pressure, complicated with hypertension, hypokalemia, elevated urinary potassium excretion, and increased aldosterone-to-renin concentration ratio (ARR), along with a captopril suppression rate of -23.6%. Imaging revealed left adrenal hyperplasia. Genetic sequencing revealed: a heterozygous mutation c.5324-19G>A was identified in the IVS31/IC30 region of the CACNA1H gene. Family screening revealed that 4 family members-his mother, older brother, younger brother, and nephew-carried the variant. Among them, 3 individuals (excluding the nephew) presented with hypertension and elevated ARR, leading to a confirmed diagnosis of familial hyperaldosteronism type Ⅳ. Among 4 cases, including the proband, 3 cases complicated hypokalemia, 3 showed adrenal hyperplasia, and 2 had early-onset cerebrovascular events. Genetic analysis confirmed this intronic variant causes RNA splicing abnormalities. Compared to previously reported pedigrees with exonic missense mutations, this family demonstrated a significantly higher incidence of cerebrovascular complications (50%). Spironolactone treatment effectively normalized blood pressure and serum potassium levels. These findings highlight the necessity of combining ARR assessment, captopril testing, and CACNA1H genetic analysis for familial hyperaldosteronism diagnosis in patients with early-onset hypertension, hypokalemia, and family history of cerebrovascular disease.