Classical Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency in Croatia between 1995 and 2006

Abstract

Aims: To evaluate the incidence, gender, symptoms and age at diagnosis among patients with classical congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency in Croatia. Methods: Data were collected retrospectively for all classical CAH patients born or electively aborted following prenatal diagnosis between 01.01.1995 and 31.12.2006 and were compared with the data of the previously conducted study evaluating CAH patients discovered between 1964 and 1984. Results: During a 12-year period, 34 classical CAH patients were born. There were 20 salt-wasting (SW) (12 females/8 males) and 14 simple virilizing (SV) patients (7 females/7 males). If 3 female fetuses, electively aborted, were added, that would be a total of 37 CAH patients. With 532,942 live births and 34 CAH patients born over this period, incidence of classical CAH was estimated to 1:15,574 or 1:14,403 if 3 electively aborted fetuses were included. The lower incidence of SW boys compared to SW girls (8:12) and similar number of SW and SV boys (8:7) indicate that substantial proportion of SW boys die unrecognized. Owing to better health care, diagnosis was established significantly earlier in SW and SV girls compared to the period of 1964–1984 (p < 0.003). During 1995–2006, none of the patients died following the diagnosis of CAH, and there was no erroneous sex assignment. Conclusion: Despite of improvement in health care, diagnosis of CAH in Croatia is still delayed and some of the patients go unrecognized or die. Therefore, we think that the results of our study support the need for the introduction of newborn screening.

Association of HLA alleles and haplotypes with CYP21A2 gene p. V282L mutation in the Croatian population

“…A significant linkage between the p.V282L mutation and the HLA‐A*33:01‐B*14:02‐DRB1*01:02 haplotype observed in our study is in concordance with previously reported results from other studies .…”

“…Linkage disequilibrium has been demonstrated to exist between particular HLA-A, -B, and -DRB1 alleles or haplotypes and CYP21A2 mutations (9). The p.V282L mutation has been reported to be associated with the HLA-B14 antigen and -DR1 antigen among patients with NC form of the disease (10)(11)(12)(13), while some other studies reported on the association with a single HLA antigen, but a combination of those HLA specificities have not been reported before (14,15).…”

Congenital Adrenal Hyperplasia—Current Insights in Pathophysiology, Diagnostics, and Management

“…Thus, a relative paucity of males in a patient population may be taken as indirect evidence of unreported deaths from salt-wasting crises. Females do outnumber males in some (12,240,241) although not all (242) retrospective studies in which CAH was clinically diagnosed without neonatal screening. Moreover, there is a greater preponderance of severe genotypes in screened infants than in those ascertained prior to screening, again suggesting extra deaths of severely affected infants prior to screening (2,243).…”

Neonatal Screening for Congenital Adrenal Hyperplasia in Turkey: A Pilot Study with 38,935 Infants

“…The majority of states in the United States (US) and more than 50 countries are currently performing NBS for CAH (5). Infant screening programs have markedly decreased the time to diagnosis, theoretically decreasing morbidity (6,7). Based on proven importance, a pilot NBS programme for CAH was initiated by the Turkish Directorate of Public Health (TDPH) on March 27, 2017 in four Turkish cities.…”