ESPE Abstracts

Background: Biallelic mutations of the CYP11B2 aldosterone synthase gene cause deficiency of aldosterone synthesis. Patients exhibit isolated deficiency of aldosterone biosynthesis, increased plasma renin activity, increased steroid precursors desoxycorticosterone, corticosterone, as well as 18-hydroxy-desoxycorticosterone, and show salt wasting and poor growth. The aldosterone synthase enzyme has 18-hydroxylase (corticosterone methyloxidase type I, CMO I) and 18-oxidase (CMO II) activity. Depending on which of these catalytic activities is predominantly affected, this leads to aldosterone synthase deficiency type 1 or type 2. CMO I deficiency is characterized by missing significant aldosterone secretion, low or normal secretion of 18-hydroxy-corticosterone (18-OHB), and patients are always found to have mutations that completely inactivate the encoded CYP11B2 enzyme. The second form (CMO II or type 2 deficiency) has low to normal levels of aldosterone, but increased levels of its immediate precursor 18-OHB.

Objective: We report seven patients from five families diagnosed with aldosterone synthase deficiency, and characterize their biochemical and clinical phenotype.

Results: All seven patients presented with failure to thrive. In three patients this was the main reason for hospital admission. Clinical deterioration with suspected sepsis and electrolyte shift was the reason in three other cases. In one case, diagnostic workup was started due to an affected sibling. Neonatal screening for inborn errors of metabolism in all of them was unremarkable. In all patients laboratory examinations showed persistent hyponatremia and hyperkalemia, decreased aldosterone, increased plasma renin, increased steroid precursors desoxycorticosterone, corticosterone as well as 18-hydroxy-desoxycorticosterone. Levels of 17-hydroxyprogesterone and adrenocorticotropic hormone found within normal ranges. Treatment was initiated with 20-25 μg/kg of fludrocortisone daily. Electrolytes and renin levels normalized within a few weeks and all patients showed rapid catch-up growth and weight gain.

Conclusion: A defect in mineralocorticoid synthesis should be part of the differential diagnoses in patients with failure to thrive and persistent abnormal serum electrolyte levels.