title: The biochemical phenotypes of two inborn errors in the biosynthesis of aldosterone.
abstract: Two inborn errors in the methyl oxidation of corticosterone to form aldosterone correspond to the two oxygenation-hydroxylation reactions required for this transformation. Both defects are characterized by overproduction of corticosterone of glomerulosa zone origin and deficient synthesis of aldosterone. In the type 1 corticosterone methyl oxidase defect (CMO I) impairment in the first step is reflected in decreased production of 18-hydroxycorticosterone while in CMO II an impaired second step is characterized by overproduction of 18-hydroxycorticosterone leading to an increased 18-hydroxycorticosterone:aldosterone metabolite ratio as a diagnostic index. This metabolite ratio may be increased somewhat in CMO I but not as much as in CMO II. The absolute value of 18-hydroxycorticosterone is a more reliable discriminator as is the corticosterone:18-hydroxycorticosterone metabolite ratio which is increased in CMO I and decreased in CMO II. On the basis of these findings, a North American kindred is reclassified as CMO I making this defect the more prevalent form in the Western Hemisphere. The two biochemical phenotypes will very likely describe different mutations in the gene encoding cytochrome P-450 CMO.
authors.affiliation: Veterans Affairs Hospital, Bronx, New York 10468.
authors.forename: S
authors.initials: S
authors.lastname: Ulick
authors.forename: J Z
authors.initials: JZ
authors.lastname: Wang
authors.forename: D H
authors.initials: DH
authors.lastname: Morton
mesh_terms: D015069:18-Hydroxycorticosterone / Q000652:urine; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000652:urine*; D000328:Adult; D000450:Aldosterone / Q000096:biosynthesis* / Q000652:urine; D002648:Child; D002675:Child, Preschool; D003345:Corticosterone / Q000652:urine; D019405:Cytochrome P-450 CYP11B2; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000652:urine; D008297:Male; D008661:Metabolism, Inborn Errors / Q000235:genetics / Q000378:metabolism* / Q000652:urine; D006899:Mixed Function Oxygenases / Q000172:deficiency* / Q000235:genetics; D010641:Phenotype
chemical_list: D000305:Adrenal Cortex Hormones; D000450:Aldosterone; D015069:18-Hydroxycorticosterone; D006899:Mixed Function Oxygenases; D019405:Cytochrome P-450 CYP11B2; C033112:corticosterone methyl oxidase I; C025352:corticosterone methyl oxidase II; D003345:Corticosterone; D006854:Hydrocortisone