title: Severe hypoaldosteronism due to corticosterone methyl oxidase type II deficiency in two boys: metabolic and gas chromatography-mass spectrometry studies.
abstract: Infection-triggered, life-threatening salt-loss and hyperkalaemia developed in two male infants with wasting, inappropriately low plasma aldosterone concentrations and elevated plasma renin activity. The presumptive diagnosis of a defective terminal step in aldosterone biosynthesis was made by the presence of large amounts of 11-dehydrotetrahydrocorticosterone and its 18-hydroxylated metabolite (18-OH-THA), free 18-hydroxycorticosterone (18-OH-B) and 18-hydroxytetrahydrocorticosterone in the urine of both patients. The diagnosis of corticosterone methyl oxidase type II (CMO II) deficiency was confirmed by an elevated urinary 18-OH-THA to tetrahydroaldosterone ratio in one boy and by an elevated plasma 18-OH-B to aldosterone ratio in the other boy. Unknown steroids responsible for the salt-loss were not identified. Sodium supplementation but not short-term high dose oral 9 alpha-fluorcortisol (FF) normalized the hyponatraemia in one patient, in whom sodium (Na+)/potassium (K+) co-transport was decreased. Both patients eventually received long-term FF treatment to prevent impairment of longitudinal growth caused by chronic salt-loss. The diagnosis of CMO II deficiency should always be confirmed by elevated precursor-product ratios in urine or plasma, using radioimmunoassays with prior chromatographic separation. Metabolic studies as the short-term response of serum Na+ to high dose FF may not be helpful in differentiating aldosterone biosynthetic defects from end-organ resistance to mineralocorticoids.
authors.affiliation: Department of Paediatrics and Adolescent Medicine, University GHS Essen, Republic of Germany.
authors.forename: B P
authors.initials: BP
authors.lastname: Hauffa
authors.forename: J
authors.initials: J
authors.lastname: Sólyom
authors.forename: E
authors.initials: E
authors.lastname: Gláz
authors.forename: C H
authors.initials: CH
authors.lastname: Shackleton
authors.forename: G
authors.initials: G
authors.lastname: Wambach
authors.forename: P
authors.initials: P
authors.lastname: Vecsei
authors.forename: H
authors.initials: H
authors.lastname: Stolecke
authors.forename: J
authors.initials: J
authors.lastname: Homoki
mesh_terms: D003348:Cortisone / Q000031:analogs & derivatives / Q000627:therapeutic use; D019405:Cytochrome P-450 CYP11B2; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D006994:Hypoaldosteronism / Q000209:etiology* / Q000378:metabolism / Q000628:therapy; D007223:Infant; D008297:Male; D008661:Metabolism, Inborn Errors / Q000150:complications / Q000175:diagnosis* / Q000628:therapy; D006899:Mixed Function Oxygenases / Q000172:deficiency*; D011188:Potassium / Q000378:metabolism; D012083:Renin / Q000097:blood; D012463:Saliva / Q000737:chemistry; D012964:Sodium / Q000378:metabolism; D013256:Steroids / Q000032:analysis / Q000097:blood
chemical_list: D013256:Steroids; C033001:9-fluorocortisone; D012964:Sodium; D006899:Mixed Function Oxygenases; D019405:Cytochrome P-450 CYP11B2; C025352:corticosterone methyl oxidase II; D012083:Renin; D011188:Potassium; D003348:Cortisone