Aldosterone production despite absence or defectiveness of the CYP21 genes in two patients with salt-losing congenital adrenal hyperplasia caused by steroid 21-hydroxylase deficiency

Aldosterone and cortisol were found in plasma samples from two patients with salt-losing congenital adrenal hyperplasia caused by steroid 21-hydroxylase deficiency. One patient had a CYP21 gene deletion on one chromosome and a mutation causing erroneous mRNA splicing on the other. The other patient had a CYP21 gene deletion on one chromosome and a large scale conversion of CYP21 to CYP21P on the other. All CYP21P-like genes in these patients were defective, since they carried a deleterious 8 bp deletion in the third exon, After HPLC purification of the patients' plasma samples, cortisol was no longer detectable in the radioimmunoassay, but aldosterone levels were still within or slightly above the normal reference range. Aldosterone dropped to very low levels after steroid replacement therapy had taken effect. In at least one of these patients, the genetic defect rules out normal functioning of the adrenocortical steroid 21-hydroxylase, which implies involvement of an alternative enzyme system.