DIFFERENTIAL D'AGNOSIS OF TERMINAL ALDOSTERONE BIOSYNTHESIS DEFECTS

Abstract

Terminal aldoslerone biosynthesis (TAB) from 11-deoxycorticosterone (DOC) requires 11-hydroxylation, 18-hydroxylation, and finally oxidation at C-18. One single P450 catalyzes all 3 steps encoded by the gene CYP11B2. The two known TAB defects are characterized by excess corticosterone (B) and deficient Aldo. CMO (corticosterone methyl oxidase deficiency) type I has low, while CMO II has elevated 18-OHB levels. Since 1982, we diagnosed 3 pts with CMO I and 5 with CMO II by multisteroid analysis (RIA after extraction and automated gel chromatography). Both types could be clearly differentiated by B/18-OHB and 18-OHB/ Aldo ratios which ranged 32-136 and 11.5-16.7 in CMO I, and 1.9-11.2 and 22-286 in CMO II pts, respectively. The ratio B/18-OHB appears particularly useful in CMO cases with undetectably low Aldo levels and noncalculable 18-OHB/Aldo ratios. In 2 of our 5 CMO II pts we did not find any of the 2 known mutations described in such pts from Iranian-Jewish origin. Genomic cloning and sequence analysis of the CYP11B2 genes in our CMO I and II pts may reveal the nature of the marked biochemical differences found in TAB disorders. Supported by the Thyssen Foundation

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