Inborn Error in the Terminal Step of Aldosterone Biosynthesis: Corticosterone Methyl Oxidase Type II Deficiency in a North American Pedigree

Johannes D. Veldhuis, Howard E. Kulin, Richard J. Santen, Thomas E. Wilson, James C. Melby, Johannes D. Veldhuis

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

Profound salt wasting developed in a male infant who had marked reductions in serum and urinary aldosterone concentrations despite striking hyperreninemia. Coincident elevations in plasma and urinary levels of specific 18-hydroxysteroids localized the defect to corticosterone methyl oxidase Type II, the adrenal enzyme responsible for the final step of aldosterone synthesis. Salt replacement but not hydrocortisone ameliorated the clinical and metabolic abnormalities. Evaluation of 33 other family members disclosed the biochemical disorder in six other subjects who were affected in an autosomal-recessive pattern with variably severe clinical manifestations and abnormal ratios of 18-hydroxycorticosterone (or its metabolites) to aldosterone. This inborn error in aldosterone biosynthesis must be distinguished from other heritable, salt-losing defects in adrenal steroidogenesis. (N Engl J Med. 1980; 303:117–21.) INBORN errors in adrenal steroidogenic enzymes may produce life-threatening impairment of salt and water homeostasis.1,2 Cortisol deficiency and variable genital ambiguity ensue unless the enzymatic lesion impinges selectively on the distal mineralocorticoid pathway in the zona glomerulosa.314 In the latter condition of isolated hypoaldosteronism, a defect may reside in either of two mixed-function oxidases, corticosterone methyl oxidase Type I or II (CMO I or CMO II), which are associated with the penultimate and ultimate steps, respectively, in aldosterone biosynthesis.15,16 Abnormalities at either of these loci produce hyperkalemia and hyponatremia associated with metabolic acidosis in the neonate, failure to thrive in.

Original languageEnglish (US)
Pages (from-to)117-121
Number of pages5
JournalNew England Journal of Medicine
Volume303
Issue number3
DOIs
StatePublished - Jul 17 1980

ASJC Scopus subject areas

  • Medicine(all)

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