Combined 21-hydroxylase and 11beta-hydroxylase deficiency: patient report and molecular basis

A female newborn (46, XX) with ambiguous genitalia was initially diagnosed by biochemical criteria as having classical congenital adrenal hyperplasia caused by 11beta-hydroxylase deficiency. Shortly after effective treatment was administered, she developed a salt-wasting crisis with severe electrolyte imbalance. DNA analysis revealed a homozygous splice mutation in the second intron of the CYP21 gene, for which both parents were heterozygous. No mutations were found in the entire CYP11B1 gene, thus proving that the 11beta-hydroxylase deficiency was not caused by a gene mutation but rather was a secondary event, possibly due to androgen suppression of 11beta-hydroxylase activity.