ALDOSTERONE SYNTHASE DEFICIENCY FROM HOMOZYGOUS CYP11B2 MUTATION PRESENTING WITH SALT WASTING CRISIS AND FAILURE TO THRIVE IN AN INFANT
Journal
Macedonian Journal of Anaesthesia
Date Issued
2025-12-17
Author(s)
Nikchevska, Natasha
Palchevska Kocevska, Snezhana
Spasevska, Simonida
DOI
10.55302/MJA2594138n
Abstract
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: mitted 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.
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: mitted 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.
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