ACQUISITION OF ALDOSTERONE BIOSYNTHETIC CAPACITY IN CONGENITAL ADRENAL HYPERPLASIA WITH HOMOZYGOUS DELETION OF THE GENE ENCODING P450/C21

Abstract

Salt-wasting congenital adrenal hyperplasia due to 21-hydroxylase (21-OHase) deficiency has been associated with deletion of the active structural gene for the adrenal enzyme. We report a patient with apparent homozygous deletion of the active adrenal 21-OHase gene (OH21B), i.e., complete absence of 3.7 kb Taq I fragment on genomic blot hybridization using 21-OHase cDNA as a probe (PNAS, 81:7505, 1984), in whom aldosterone biosynthesis was absent in infancy and childhood, but was present during adolescence. Three older sibs had died of salt-wasting crisis in infancy, The neonatal period in the proband was complicated by shock, hyponatremia and hyperkalemia, treated successfully with parenteral fluids, hydrocortisone, and mineralocorticoid supplements. While receiving salt-retaining hormones at age 12 years, the patient was unable to mount an adequate response to a low sodium diet: renin was elevated (23-29 ng/ml/hr) but pH₁ aldosterone was only 1 mcg/m²/day, and serum aldo was undetectable. At age 19 years after months of discontinued mineralocorticoid therapy, low salt testing was repeated: on day 3 sodium balance was achieved when renin was 115, and pH₁ aldo was now 8.6, with serum aldo 10.9 ng/dl. This case suggests that a structural 21-OHase gene defect is necessary, but not sufficient to produce the salt-wasting phenotype. The mechanism by which 21-hydroxylase activity for aldosterone biosynthesis is acquired in this patient with a homozygous deletion of the OH21B gene remains to be elucidated.

Log in or create a free account to read this content

Gain free access to this article, as well as selected content from this journal and more on nature.com

Access through your institution

or

Sign in or create an account

Continue with Google

Continue with ORCiD