Apparent mineralocorticoid excess with a novel HSD11B2 variant: longitudinal clinical and biochemical follow-Up

Apparent mineralocorticoid excess (AME) is a rare autosomal recessive disorder caused by loss-of-function mutations in HSD11B2, leading to impaired conversion of cortisol to cortisone and inappropriate mineralocorticoid receptor activation. Early recognition is critical, as untreated disease results in progressive cardiovascular and renal complications. We describe a 2-year-old boy with severe early-onset hypertension, polyuria, polydipsia, abdominal distension, and growth retardation. Biochemistry revealed hypokalemic metabolic alkalosis with suppressed renin and low aldosterone. Renal ultrasonography demonstrated bilateral medullary nephrocalcinosis. Whole-exome sequencing identified a novel homozygous missense mutation in HSD11B2 (c.478G>A; p.Gly160Ser)-previously reported as a variant of unknown significance. Targeted therapy with spironolactone, a thiazide diuretic, potassium supplementation, and adjunct antihypertensives achieved normalization of blood pressure and potassium levels, resolution of alkalosis, and significant catch-up growth over 6 months, with stable renal function. This case expands the mutational spectrum of HSD11B2 and demonstrates that early genetic confirmation and tailored therapy can reverse biochemical abnormalities, promote growth, and prevent long-term sequelae. AME should be considered in children with low-renin, low-aldosterone hypertension, particularly in consanguineous populations.