Hla and Hormonal Data for Identification of Heterozygotes in 11?- And 17?-Hydroxylase Deficiency Syndromes

Abstract

1. In previous studies, baseline and ACTH-stimulated hormone levels, plus HLA genotyping, have been used to detect heterozygous carriers in congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHDS). 2. In the present study similar parameters were determined in a family of four including two children with CAH due to 11 beta-hydroxylase deficiency (11-OHDS), and a family of twelve including three sibs (two females, one genotypically male) with CAH due to 17 alpha-hydroxylase deficiency (17-OHDS). 3. HLA typing showed affected sibs with 11-OHDS to differ in one of their haplotypes. No significant differences in basal and ACTH-stimulated steroid levels were seen between the parents (obligate heterozygotes) and the general population. 4. In 17-OHDS, affected members differed from one another in one to two haplotypes; one patient had identical HLA profiles with two of the normal siblings, as did the genotypically male patient with two others; each of the other healthy siblings had one haplotype found in two of the affected subjects. The genes responsible for 11-OHDS and 17-OHDS--in contrast with 21-OHDS--do not appear to be HLA-linked. However, the measurement of ACTH-stimulated corticosterone levels may be useful, since the gene responsible for 17-OHDS seems to be expressed hormonally in the heterozygous state.

Clinical perspectives in congenital adrenal hyperplasia due to 11β-hydroxylase deficiency

“…Contrary to 21OHD, the heterozygotes from families of patients of classic or NC 11βOHD have no significant differences in HLA genotyping or hormonal profile compared to control population [58,59,86,87]. However, there are two mutations in heterozygous carriers (p.R366C, p.T401A) with evidence of reduced CYP11B1 activity by 23 to 37%, respectively [32].…”