GENOTYPE IN THE DIAGNOSIS OF 21-HYDROXYLASE DEFICIENCY: WHO SHOULD UNDERGO CYP21A2 ANALYSIS?

Cavarzere P, Vincenzi M, Teofoli F, Gaudino R, Lauriola S, Maines E, Camilot M, Antoniazzi F.

Source

Pediatric Clinic, Department of Life and Reproduction Sciences, University of Verona, Verona, Italy.

Abstract

Aims: to confirm the diagnosis of 21-hydroxylase deficiency (21-OHD) by the analysis of CYP21A2 gene in infants with clinical and/or biochemical features of 21-OHD in order to clarify which patients to submit to genetic analysis; to analyze the genotype-phenotype concordance in these infants. Subjects and Methods: We studied 25 children with clinical and/or biochemical features of 21- OHD. All of them and their parents were submitted to genetic analysis of CYP21A2. Patients were classified in 3 groups according to mutations' severity: severe (group A), moderate (group B) or mild (group C). Results: CYP21A2 gene mutations were found in 17 children. Whereas all infants of groups A and B presented a classic form of 21-OHD, children of group C had a non classical form of 21-OHD. Four infants resulted heterozygotes and 4 children were wild-type. A girl clinically presenting a non classical form of 21-OHD resulted compound heterozygote with one of the mutations not described in literature (R25W) and whose residual enzymatic activity is not already known. All affected children presented a 17-OHP level after ACTH stimulation greater than 100 nmol/L. We found an optimal concordance between 17-OHP levels after ACTH test and genotype. Conclusions: CYP21A2 analysis permitted to confirm the diagnosis of 21-OHD in 68% of our children. To improve this percentage we suggest to perform the CYP21A2 analysis only when 17- OHP after ACTH test is greater than 100 nmol/L. Moreover, we found an optimal genotypephenotype concordance in the 21-OHD patients.