THE ASSOCIATION BETWEEN CONGENITAL ADRENAL-HYPERPLASIA AND HLA IN SOUTHERN ITALY

In this paper, we report on our studies carried out on families from Southern Italy having one or more children suffering from congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. The work was initially aimed at the confirmation of the linkage of the enzyme deficiency to the HLA complex in our population, after the discovery of Dupont et al. in 1977. The number of typed families was subsequently extended to focus on the possible association of the disease with HLA alleles and to correlate different clinical forms of the disease to HLA patterns. Aside from the usefulness of HLA typing for clinical purposes, the study seemed of interest because of the genetic peculiarities of Southern Italian populations, which had been shown to diverge from other European Caucasoid ethnic g~oups.~ Our study included 13 families with a total of 72 members, 19 of which were afflicted with the so-called "classical" form of CAH. In all patients, the disease was ascertained by clinical and biochemical means. All family members were typed for nearly all known HLA specificities (HLA-A, -B, and -C loci), as recognized at the 7th and 8th International Histocompatibility Testing Workshops. In some families, DR, Bf, and C2 phenotypes were also determined by standard methods. In each of the families studied, the affected siblings are HLA-identical. In 3 out of 13 families, a male affected child, clinically apparently normal, was detected after HLA-typing and assay of serum 17-hydroxyprogesterone (1 7-OH-P). These individuals should probably not be assimilated to "cryptic" patients as indicated in the literature. They actually are HLA-identical to symptomatic patients in the same family, and are, apparently, homozygotes for the pathologic trait.