TY - JOUR
T1 - Inborn Error in the Terminal Step of Aldosterone Biosynthesis
T2 - Corticosterone Methyl Oxidase Type II Deficiency in a North American Pedigree
AU - Veldhuis, Johannes D.
AU - Kulin, Howard E.
AU - Santen, Richard J.
AU - Wilson, Thomas E.
AU - Melby, James C.
AU - Veldhuis, Johannes D.
PY - 1980/7/17
Y1 - 1980/7/17
N2 - 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.3–14 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.
AB - 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.3–14 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.
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U2 - 10.1056/NEJM198007173030301
DO - 10.1056/NEJM198007173030301
M3 - Article
C2 - 6991942
AN - SCOPUS:0018860824
SN - 0028-4793
VL - 303
SP - 117
EP - 121
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 3
ER -