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.

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