EVIDENCE FOR ENDOCRINOLOGIC ABNORMALITIES IN HETEROZYGOTES FOR ADRENAL 11-BETA-HYDROXYLASE DEFICIENCY OF A FAMILY WITH THE R448H MUTATION IN THE CYP11B1 GENE

In about 5% of cases of classical congenital adrenal hyperplasia, ster oid 11 beta-hydroxylase deficiency is the underlying defect. In two pu blications, no biochemical abnormalities have been reported in obligat e heterozygotes for 11 beta-hydroxylase deficiency. We found the typic al plasma steroid pattern of 11 beta-hydroxylase deficiency and identi fied the R448H mutation in the CYP11B1 gene in a boy presenting with p seudoprecocious puberty at age 2 yr. Both parents and an older sister were genotyped and were heterozygous carriers for the R448H mutation i n CYP11B1. In contrast to the data reported in the literature, we foun d increased responses of plasma 11-deoxycortisol and 11-deoxycorticost erone in the short term ACTH test in the three family members heterozy gous for the R448H mutation.