Endocrine Abstracts

Background: CYP11B2 encodes a steroid 11/18-β-hydroxylase that functions in mitochondria in the zonaglomerulosa of the adrenal cortex to synthesize the mineralocorticoid aldosterone. The enzyme catalyzes three necessary reactions: 11-β-hydroxylation of 11-deoxycorticosterone (11-DOC) to corticosterone, 18-hydroxylation of corticosterone to 18-hydroxycorticosterone (18-OHB); and 18-oxidation of 18-hydroxycorticosterone to aldosterone. Aldosterone synthase (CYP11B2) deficiency is an autosomal recessive disorder associated with a defect in aldosterone biosynthesis. The clinical presentation and severity of the condition varies with age. Newborns exhibit salt wasting in the first few weeks of life with failure to gain weight. Adults may present with hyperkalaemia and postural hypotension.

Case: We report the case of an infant who presented with failure to thrive and poor feeding. At 3 months of age, his weight was 3.02 kg (−4.3 SDS), having gained just 100 g since birth. Biochemistry revealed hyponatraemia (Na⁺124 mmol/l), hyperkalaemia (K⁺6.3 mmol/l), and raised urea (9.7 mmol/l). After correcting the hyperkalemia, he was investigated thoroughly. The plasma renin activity (PRA) was 12 nmol/l per h; slightly elevated. Cortisol was normal and aldosterone measured 470 pmol/l (NR 100–800 pmol/l). Raised urinary corticosterone metabolites were detected suggesting an aldosterone synthesis defect, thus fludrocortisone was initiated. As the response was suboptimal and diagnosis remained unclear, he was admitted into a controlled environment and fludrocortisone withheld. The subsequent PRA was found to be raised at 100 nmol/l per h strongly supporting the diagnosis of an aldosterone biosynthetic defect. Genetic analysis revealed compound heterozygosity for a novel CYP11B2 mutation: (c.1471C>T (p.Pro491Ser)) and a previously reported mutation (c.541C>T (p.Arg181Trp)). He responded to recommencement of fludrocortisone, sodium supplementation and dietetic support with good catch-up growth and normal development.

Conclusion: Although rare, aldosterone synthase deficiency should be suspected in infants presenting with salt-wasting. Long-term prognosis is good once fludrocortisone is commenced. If uncorrected, the resulting hypotension, hyponatraemia, and hyperkalaemia may prove devastating.