Genotype-phenotype association in congenital adrenal hyperplasia due to 21-hydroxylase deficiency in children.

Objective: The purpose of this study was to investigate the clinical manifestation of various forms of congenital adrenal hyperplasia (CAH) in children of the Republic of Kazakhstan, depending on their genotype.

Design: The study analysed 50 patients diagnosed with CAH from 7 regions of Kazakhstan with different ethnic origins: 35 Kazakhs (70.0%), 8 Russians (16.0%), 2 Turks (4.0%), 2 Ukrainians (4.0%), 2 Uzbeks (4%), 1 Uighur (2%). All the children studied were from 0 to 18 years old, and their average age was 5.7 years ±3.9. In addition, all children were divided into groups depending on the form of the disease according to the phenotypic manifestation of the disease: salt-wasting (SW) and simple virile (SV) forms. Most of the patients suffered from SW - 32 (64.0%), and a smaller group had SV - 18 (36.0%), also one boy with SW was diagnosed with TART syndrome.

Measurements: 50 Kazakh children with the classical form of CAH were analysed. Depending on the severity of the mutations, patients were divided into 4 groups: zero groups (the most severe mutations), A, B, and C.

Results: According to the results of the study, the salt-wasting form of CAH turned out to be more common than the simple virile form. A high correlation was observed in groups with mutations of high and moderate severity - 0 and A, while group C showed a strong variability of the phenotype. Thus, the correspondence between genotype and phenotype decreased along with the decrease in the severity of the disease.

Conclusions: The relationship between the genotype and the phenotype of both forms of CAH exists indirectly, through the activity of the 21-hydroxylase enzyme. Mutations in the CYP21A2 gene affect the level of the synthesized enzyme, which, in turn, determines the degree of hormone production in the blood.