ALDOSTERONE SYNTHASE DEFICIENCY FROM HOMOZYGOUS CYP11B2 MUTATION PRESENTING WITH SALT-WASTING CRISIS AND FAILURE TO THRIVE IN AN INFANT

Abstract

Introduction:
Aldosterone synthase deficiency (ASD) is a rare autosomal recessive disorder caused by pathogenic variants in the CYP11B2 gene, leading to impaired aldosterone synthesis and life-threatening salt-wasting. We present a case of an infant with failure to thrive, dehydration, and electrolyte imbalance, diagnosed through next-generation sequencing.

Material and Methods:

A 9-month-old male infant was admitted with persistent vomiting, constipation, and a10% weight loss. Laboratory evaluation showed severe hyponatremia (116 mmol/L), hyperkalemia (6.5 mmol/L), hypochloremia (87 mmol/L), and metabolic alkalosis. Differential diagnosis included gastrointestinal loss, renal salt-wasting, cystic fibrosis, celiac disease, and congenital adrenal hyperplasia. Normal 17-hydroxyprogesterone excluded classical CAH. Next-generation sequencing was performed.

Results:
A homozygous pathogenic variant c.554C>T (p.Thr185Ile) in CYP11B2 confirmed ASD. Treatment with fludrocortisone and sodium supplementation resulted in rapid correction of electrolytes and improved growth. Follow-up at 3.5 years showed normal growth (14.5 kg, 103 cm), stable electrolytes, and normal development, with only mild transient hyponatremia during illness.

Conclusion:
ASD should be considered in infants with vomiting, dehydration, and combined hyponatremia–hyperkalemia when CAH is excluded. Early diagnosis and mineralocorticoid therapy prevent complications and support normal development.