A NEW HEREDITARY DEFECT IN THE BIOSYNTHESIS OF ALDOSTERONE: URINARY C21-CORTICOSTEROID PATTERN IN THREE RELATED PATIENTS WITH A SALT-LOSING SYNDROME, SUGGESTING AN 18-OXIDATION DEFECT

Abstract

Two infants with a salt-losing syndrome were observed. They were 5 and 15 weeks old on admission to the hospital. The 4 parents of these 2 patients were related. Another 14 year old child in the same family was seen at the age of 3 weeks in the hospital with the same clinical syndrome. All cases gave a good response to deoxycorticosterone acetate (DOCA). External genitalia were normal; total urinary excretion of 17-ketosteroids, 17-ketogenic steroids and 17-hydroxycorticosteroids were normal. The pedigree of the family could be traced back for 6 generations. The 6 parents of the 3 children with the salt-losing syndrome had the same 2 great-grandparents 5 generations back. Urinary C21-corticosteroid excretion showed a typical pattern in the infants and the 14 year old child. No aldosterone was detectable. There was a considerable increase in the total B compounds: corticosterone (B), 11 dehydrocorticosterone (A) and their tetrahydrometabolites (THA, THB, allo-THB). Total F compounds were normal for the corresponding age: cortisol (F), cortisone (E) and their tetrahydrometabolites (THF, THE, allo-THF). Small amounts of 11-deoxycorticosterone (DOC) were found in the two infants. At autopsy of 1 infant the adrenal glands were macroscopically normal; they weighed 2.6 and 2.3 g. Microscopically the zona glomerulosa showed a tubular and empty aspect of varying width. This familial salt-losing syndrome could be explained by an 18-oxidation defect in the biosynthesis of aldosterone. The inheritance is due to a recessive autosomal gene with clinical expression in the homozygous state.