Aldosterone synthase deficiency associated with a CYP11B2 variant of uncertain significance: Case report and literature review

Abstract

Congenital aldosterone synthase deficiency (ASD) is a rare autosomal recessive condition that causes isolated primary hypoaldosteronism. It has been associated with different pathogenic mutations of the CYP11B2 gene. We report a case of isolated primary hypoaldosteronism with a CYP11B2 variant with uncertain significance (VUS). A 10-month-old boy presented with failure to thrive and developmental delay. Biochemical testing revealed: hyponatremia (sodium, 126) mmol/L; hyperkalemia (potassium, 5.6 mmol/L); high plasma renin activity, 9670 pmol/L; and low aldosterone, <0.97 pmol/L, pointing to the diagnosis of ASD-induced primary isolated hypoaldosteronism. He substantially improved after initiating treatment with fludrocortisone and NaCl for one year and adhered to fludrocortisone till the age of 5 years; he stopped treatment for the next 2 years. He subsequently returned with dizziness, headache, nausea, and poor appetite, requiring re-treatment with fludrocortisone. This case with a CYP11B2 VUS homozygous and a relatively late presentation emphasizes that ASD-induced isolated primary hypoaldosteronism represents a complex diagnostic and therapeutic challenge.