ESPE Abstracts

Background: Nonclassical 21-hydroxylase deficiency (NC21OHD) is one of the most common monogenic diseases. Its frequency varies significantly among different ethnic groups. In Russians the frequency of NC21OHD is unknown.

Objective and hypotheses: To estimate the incidence of NC21OHD in Russia based on the carrier frequencies of the two most common mutations associated with this disease (V281L and P30L).

Method: A total of 998 randomly selected dried blood spot samples were obtained from a regional neonatal screening laboratory. All samples were collected within one calendar year. Each sample was analysed for V281L and P30L mutations in CYP21A2 using allele-specific PCR. PCR-positive samples were reanalyzed by Sanger sequencing. The frequency of homozygotes was calculated by Hardi-Weinberg equation.

Results: Heterozygous V281L mutations were detected in 39 of 998 samples (carrier frequency, 1:24), while P30L mutation was detected in none. Minimal frequency of NC21OHD, as estimated by theoretical frequency of V281L homozygotes, was 1:2206. In contrast, the incidence of NC21OHD suspected by dried blood spot 17OHP levels on the neonatal screening was 1:27990.

Conclusion: The study provides an estimate of the population frequency of NC21OHD in Russians and demonstrates that the majority of NC21OHD cases remain undiagnosed.