ESPE Abstracts

Introduction: The aldosterone synthesis is dependent on aldosterone synthase (AS), an enzyme encoded by the CYP11B2gene, one of the cytochrome P450 enzymes (P450c11Aldo). It catalysis the final steps of adosterone biosynthesis.

Case: A 10 days old boy is presented with poor feeding, jaundice and weight lost. He was born from a 35 years old mother, as 4 th children, from consanguineous parents. One sister and one brother of the mother were died during early infancy from unknown causes. On physical examination his weight was 2600 gr, heart rate 170 /min, blood pressure 72/ 42 mmHg and dehydrated. On laboratory examination, sodium 123 mmol/l, K: 8.66 mmol/l, pH: 7.15 HC03: 13mmol/L. He was hospitalized in intensive care unit and prompt treatment with fludrocotisone 0.2 mg and NaCL was started (8 mEq/kg). First hormonal work up revealed Renin> 150 ng/mL/h, aldosterone < 0,5 ng/dL (5-99), cortisol 24.95 mg /dl, ACTH 2.10 pg/ml and 17-hydroxy progesterone: 0,84 ng/mL. He was diagnosed as aldosterone synthehase deficiency and discharged with NaCL (4*0,5 gr) and fludrocortisone (0,2 mg). Genetic analysis was performed with direct DNA sequence analysis of the entire coding regions of the CYP11B2, c.1382T>C (P.L1461p) homozygote mutation was detected. This mutation was detected in a Turkish patient with CMO I deficiency, the mutation involved a putative heme binding site. In vitro functional expression studies showed that the L461P substutition totally abolished the 18-hydroxylase activity required for conversion of 11-deoxycorticosterone to aldosterone, even though the mutant product was detected in the mitochondrial fraction of transfected cells.

Conclusion: Mineralocorticoid deficiency can be presented with severe salt-wasting with important signs and symptoms of dehydration, feeding difficulties and failure to thrive in the neonatal period. Clinical presentation with typical biochemical profile with hyponatremia, hyperkalemia, normal cortisol and sex steroids, high plasma renin levels and unappropriated normal or low aldosterone levels must suggest the disease. The urgent treatment was life saving and clinical severity decrease with age. Adults are frequently asymptomatic despite no mineralocorticoid therapy. This fact can be associated with a gradual declining dependency on aldosterone during lifetime for normal ionic imbalance due to possible extra-adrenal compensatory mechanisms and alternative ACTH-dependent pathways for mineralocorticoid biosynthesis.