'Cryptic' form of congenital adrenal hyperplasia due to 21-hydroxylase deficiency in the Yugoslav population

Abstract

Five individuals with the asymptomatic, 'nonclassical', 'cryptic' form of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase (21-OH) deficiency from 5 unrelated families were discovered during hormonal studies and HLA-typing performed in a series of 24 families with CAH due to 21-OH deficiency. Four of the 5 individuals with the 'cryptic' form of CAH belong to families where the index case was a patient with the classical form of CAH due to 21-OH deficiency. The fifth one originated from a family where the index case was a girl with the 'non-classical', 'late-onset' form of the disease. All the 5 individuals had no clinical symptoms in spite of clearcut biochemical signs of 21-OH deficiency: increased 17-OH-progesterone (17-OHP), dehydroepiandrosterone and androstenedione levels, particularly after ACTH-stimulation. The 17-OHP response upon ACTH stimulation of heterozygotes for this 'non-classical' form of 21-OH deficiency did not differ from the response of heterozygous individuals for the classical form of the disease. The results of this study confirm the hypothesis that individuals with the 'cryptic' form of CAH due to 21-OH deficiency are genetic compounds bearing one allele for the severe, classical form, and on the homologous locus, another one for the mild 'nonclassical' form of CAH due to 21-OH deficiency. Their genotype was 21-OHsevere/21-OHmild, The gene for 'cryptic' 21-OH deficiency, as well as the gene for the classical form of the disease is linked to the HLA system, but in our population apparently it is not in genetic disequilibrium with the antigens B 14 DR 1, as it was shown for other populations studied up to now.

An update on the frequency of nonclassic deficiency of adrenal 21-hydroxylase in the Yugoslav population

“…Reference hormone data of the three families whose members un¬ derwent the 360-min ACTH test are provided from the previous publication of Dumic et al (6). Reference hormone data of the three families whose members un¬ derwent the 360-min ACTH test are provided from the previous publication of Dumic et al (6).…”

“…In the same 49 families, HLA linkage for the nonclassic 21-hydroxylase deficiency alíele was analyzed by comparing the frequen¬ cies of HLA-A, HLA-B, and HLA-DR antigen types found in the 9 nonclassic parental haplotypes with fre¬ quencies of the same antigen types in the 89 unaffected parental haplotypes. Data from families A, B, D, E and F have been published previously (6,7). The restriction of permitting only haplotypes from classic index case fami¬ lies is followed here as in the earlier studies (2).…”

“…A second, computer-assisted study conducted on basically the same test population, somewhat ex¬ panded in members and in family number (N=220), was undertaken to determine the fre¬ quency of the disease by a different methodology (2). The lack of B14 association with the occurence of disease in Yugoslavs has been reported elsewhere (6,7). Because the completeness of subject selection was not known, a low, intermediate and high ascertainment probability was assumed in the analysis in different trials.…”

Differential Diagnosis of Hyperandrogenism in Women with Polycystic Ovary Syndrome

“…However, a higher frequency of NCCAH due to 21-hydroxylase defi ciency was reported in certain ethnic groups. These include Ashkenazi Jews (1:27), Hispanics (1:40), Slavs (1:50) and Italo-Americans (1:300) ( Dumic et al, 1985 ;Dumic et al, 1990 ;Sherman et al, 1988 ;Speiser et al, 1985 ;Zerah et al, 1990 ). Therefore screening for this disorder should always be performed in these populations.…”

Nonclassic 21-Hydroxylase Deficiency in Croatia

“…Among the males, all five asymptomatic males of reproductive age were fertile (#12, 13,14,15,18). Among the four females of reproductive age who were fertile, two (#4, 7) carried the exon 7 mutation, and two did not (#1, 3).…”