Biochemical diagnosis and management of corticosterone methyl oxidase type II deficiency.
Corticosterone methyl oxidase deficiency type II (CMO type II deficiency) is an autosomal recessive disorder characterized by a defect in the terminal step of aldosterone biosynthesis. Previous reports emphasized the diagnostic utility of elevated urinary ratios of 18-hydroxytetrahydro-compound A to tetrahydro-aldosterone, which are primary metabolites of 18-hydroxycorticosterone (18-OHB) and aldosterone, respectively. Limited data suggest that plasma ratios of 18-OHB to aldosterone are also abnormal in affected individuals. We report serum steroid profiles in two siblings with CMO type II deficiency. Serum levels of aldosterone precursors were elevated in both patients before treatment. In particular, the serum ratios of 18-OHB to aldosterone were greatly elevated and declined to normal levels during mineralocorticoid replacement. The possibility of heterozygote detection using this ratio is suggested. We also confirm previous reports of a detrimental effect on linear growth rate after cessation of mineralocorticoid therapy despite maintenance of normal serum electrolytes. This effect is associated with biochemical evidence of chronic salt depletion. Based on our observations, we recommend that serum 18-OHB to aldosterone ratios be routinely measured for the diagnosis and management of patients with CMO type II deficiency.
D000305:Adrenal Cortex Hormones / Q000097:blood*; D000450:Aldosterone / Q000096:biosynthesis; D019405:Cytochrome P-450 CYP11B2; D005260:Female; D005438:Fludrocortisone / Q000627:therapeutic use; D006580:Genetic Carrier Screening; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008661:Metabolism, Inborn Errors / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy; D006899:Mixed Function Oxygenases / Q000172:deficiency*; D012016:Reference Values; D012083:Renin / Q000097:blood
D000305:Adrenal Cortex Hormones; D000450:Aldosterone; D006899:Mixed Function Oxygenases; D019405:Cytochrome P-450 CYP11B2; C025352:corticosterone methyl oxidase II; D012083:Renin; D005438:Fludrocortisone