Significance of a Three-Missense Pathogenic Variant in the Substrate-Binding Lesion in a Subject With 21-Hydroxylase Deficiency: A Case Report

Congenital 21-hydroxylase deficiency (21-OHD) represents a healthcare challenge during the transition from childhood to adulthood for young adults with special needs. Although numerous countries have implemented newborn screening programs for 21-OHD, a significant number of patients may reach adulthood without undergoing genetic testing. In this report, we present a case of a 26-year-old Japanese woman with 21-OHD, who was referred to our hospital for the transition from childhood to adulthood in young adults with special healthcare needs (YASHCN). At that time, she had no complaints, but she wanted to undergo a thorough examination for a correct diagnosis of 21-OHD. The genetic test showed a novel new variant of the three-cluster mutation, p.[Ile237Lys; Val238Glu; Met240Lys]. Our findings highlight the significance and reaffirmation of the three-missense pathogenic variant in the CYP21A2 gene in determining the enzyme activity of 21-hydroxylase and the onset of 21-OHD.