Homozygous deletion of arginine-173 in the CYP11B2 gene in a girl with congenital hypoaldosteronism - Corticosterone methyloxidase deficiency type II

The first child of consanguineous parents presented with failure to thrive and feeding problems at age 6 weeks. Important laboratory findings were low plasma sodium and elevated potassium and renin. Salt wasting was caused by an enzymatic defect in the terminal aldosterone biosynthesis, The biochemi cal diagnosis of corticosterone methyloxidase (CMO) deficiency type II was established on the basis of plasma multisteroid analysis, showing a patholo gic increase of 18-OH-corticosterone/aldosterone ratio. Sequence analysis o f the CYP 11B2 gene which encodes aldosterone synthase (P450c11Aldo), the e nzyme required for the terminal steps in aldosterone biosynthesis, revealed a hitherto undescribed homozygous deletion of codon 173. CYP11B2 is polymo rphic at this position, encoding arginine or lysine. Both parents were hete rozygous carriers of the mutation. Amino acid residue 173 in P450c11Aldo is positioned in alpha-helix D, We presume that the secondary structure of th e enzyme is changed by the single amino acid deletion, This report describe s a novel mutation in the CYP11B2 gene, the third known mutation associated with CMO deficiency type II.