Publication:

A rare cause of salt wasting and failure to thrive in infancy: case of aldosterone synthase deficiency

Aldosterone synthase deficiency (ASD) is a rare autosomal recessive disorder caused by pathogenic variants in CYP11B2 that impair aldosterone biosynthesis. It presents with salt-wasting, hyponatremia, hyperkalaemia and failure to thrive in infancy and can be life‑threatening if not recognized and treated. We report an infant with early-onset salt-wasting and a novel CYP11B2 variant. A 56‑day‑old female, presented with poor weight gain and dehydration. Laboratory investigations showed hyponatremia, severe hyperkalaemia, metabolic acidosis and mildly elevated 17‑hydroxyprogesterone; cortisol and ACTH were normal. Plasma aldosterone was low (4.4 ng/dl) with low‑normal renin activity (2.39 ng/ml/h). Clinical exome sequencing identified a homozygous c.542G>C (p. Arg181Pro) likely pathogenic variant in CYP11B2, consistent with aldosterone synthase deficiency. Acute management included intravenous fluids, sodium supplementation and anti‑hyperkalemic measures. The child received empirical hydrocortisone initially and was started on fludrocortisone (200 µg/day) with oral sodium chloride supplementation. On follow‑up the infant demonstrated appropriate weight gain and normal development. ASD should be considered in infants with salt‑wasting and failure to thrive without virilization. Prompt recognition, acute electrolyte correction, and mineralocorticoid replacement lead to favourable short‑ and long‑term outcomes. Genetic testing confirms the diagnosis and enables counselling for recurrence risk.