Incidence of classical 21-hydroxylase deficiency and distribution of CYP21A2 mutations in Estonia

Aims: To determine the incidence of classical 21- hydroxylase deficiency ( 21- OHD) in Estonia from 1978 to 2004, and describe their phenotype and genotype. Methods: All Estonian endocrinologists informed us about their patients with 21- OHD. The diagnosis was confirmed in 20 patients, who were all screened for 8 common mutations of the CYP21A2 gene. Results: The 27-year period incidence was 1: 25,500. The incidence from 1992 was 1: 16,100, which more accurately reflects the real situation in Estonia. The salt-wasting form ( SW) was diagnosed in 14 ( 7 males) and the simple virilizing form in 6 patients ( 1 male). The median age at diagnosis of the SW form was 30 days in males and 2 days in females. The investigation of 34 unrelated alleles showed that a common deletion/ conversion was the most frequent mutation in our group ( 7/34). Six other mutations were present: p. Ile172Asn ( 5/34), 8-bp deletion ( 3/34), intron-2 splice mutation ( 3/ 34), p. Arg356Trp ( 3/ 34), p. Gln318X ( 3/ 34) and a small conversion ( 2/ 34). Mutations in 8 alleles remained uncertain. Conclusions: The incidence of classical 21- OHD in Estonia in 1992 2004 was 1: 16,100. The genotype of our patients is similar to those from other Caucasian populations. The relatively late age at diagnosis and the skewed female: male ratio supports the need for newborn screening for 21- OHD. Copyright (c) 2008 S. Karger AG, Basel.