Abstract

Objective: This study aimed to demonstrate the potential of integrating genetic and biochemical approaches for the rapid and definitive diagnosis of congenital adrenal hyperplasia.

Case presentation: We report the case of a 5-year-old boy presenting with early puberty and significantly advanced bone age. Due to a strong suspicion of congenital adrenal hyperplasia, the patient underwent diagnostic evaluation incorporating both biochemical and genetic analyses.

Results: Biochemical analysis using ultra-performance liquid chromatography–tandem mass spectrometry revealed a marked accumulation of 17-hydroxyprogesterone, with the steroid profile confirming a pattern characteristic of 21-hydroxylase deficiency. Sanger sequencing identified the pathogenic variant c.515T>A (exon 4) in a heterozygous state, while multiplex ligation-dependent probe amplification detected a heterozygous deletion of exons 1, 3, 4, 6 and 7 in the CYP21A2 gene. Parental segregation analysis showed that the c.515T>A variant was inherited from the father, whereas the large heterozygous deletion originated from the mother.