Multisteroid analysis in children with terminal aldosterone biosynthesis defects

Area of Science:

• Endocrinology
• Genetics
• Biochemistry

Background:

• Aldosterone (Aldo) synthesis involves multiple steps in the adrenal zona glomerulosa, catalyzed by a single enzyme, P450aldo (CYP11B2).
• Two inborn errors, Corticosterone methyl oxidase deficiency type I (CMO-I) and type II (CMO-II), lead to impaired aldosterone production and are rare causes of severe infant salt-wasting and failure to thrive.

Purpose of the Study:

• To evaluate the efficacy of simultaneous multisteroid analysis for differentiating CMO-I and CMO-II in infants.
• To characterize the steroid profiles associated with each CMO subtype.

Main Methods:

• Analysis of 16 infants diagnosed with CMO deficiencies over 10 years.
• Simultaneous multisteroid analysis using RIA after extraction and automated high-performance gel chromatography on small plasma samples.

Main Results:

• All patients presented with failure to thrive, hyponatremia, hyperkalemia, and increased plasma renin activity (PRA).
• Decreased aldosterone and elevated corticosterone (B) were observed in all patients.
• CMO-I (n=7) showed decreased 18-hydroxycorticosterone (18-OHB) with low 18-OHB/Aldo and high B/18-OHB ratios.
• CMO-II (n=7) showed elevated 18-OHB with high 18-OHB/Aldo and low B/18-OHB ratios.
• Elevated 18-hydroxy-deoxycorticosterone (18-OH-DOC) and deoxycorticosterone (DOC) were noted in all patients.

Conclusions:

• Simultaneous multisteroid determination is a precise method for differentiating CMO-I and CMO-II in early infancy.
• The B/18-OHB ratio is particularly useful when aldosterone or 18-OHB levels are undetectable or uncalculable.