Speakers - DEWC2025

Abstract

Abstract:

Familial hyperaldosteronism (FH) is a rare genetic cause of hypertension among the pediatric population. There are 4 subtypes of FH known uptill now. Familial Hyperaldosteronism III (FH III) has been known to present at an early age and demonstrate lower efficacy to medical management. A comprehensive systematic genotype and phenotype analysis of subjects with FH III has not been done. Here we reported a case of FH III with a novel mutation from our centre, and performed a detailed systematic review of individual patient data to characterize the phenotypic and genotypic features of the published cases of FH III. Our child presented with hypertension (grade 2) and hypokalemia at the age of 2 years. Her aldosterone was high, and had low renin levels. Adrenal imaging was normal. On genetic study, she was diagnosed as FH III with a novel mutation in KCNJ5 gene, c.441_443del (Thr149del). Our child has responded to medical management and has been doing well on spironolactone. We searched databases such as Pubmed, Google Scholar and Embase. After careful study of the relevant articles, we included 28 patients of FH III belonging to 18 families, including our case. Mean age of onset of disease among subjects with FH III was in the 1^st decade. Hypertension (100%) and hypokalemia (83%) were the most common presentation. Adrenal imaging showed bilateral adrenal hyperplasia (BAH) (54%), unilateral enlargement (12.5%) and normal adrenals (33%).  Though, surgery was the primary mode of treatment (57.1%), 39% of subjects responded to medical therapy as the first modality of treatment. The remission rate among subjects was 82.1%. After a thorough genotype-phenotype analysis, we identified that subjects with G151R, p.I157S, p.glu145gln, and T158A mutations carried the most severe phenotype, whereas mutations as G151E and Thr149del had the milder presentation. It affirms the fact that genetic study is indispensable, and carries an important role in genetic counseling, prognosis, and management decision of subjects with FH III.