Presentation, diagnosis and follow-up characteristics of 17α-hydroxylase deficiency cases with exon 1-6 deletion (founder mutation) in the CYP17A1 gene: 20-years single-center experience.

CONTEXT: 17α-hydroxylase/17,20-lyase deficiency (17OHD) is characterized by decreased sex steroids and cortisol synthesis, as well as an increased mineralocorticoid effect.

AIM: This study aimed to evaluate the clinical, biochemical, and molecular characteristics of patients with 17OHD and to discuss the diagnosis, treatment, and follow-up process.

METHODS: Age, symptoms, anthropometric measurements, blood pressure, and hormonal, biochemical, and chromosomal analysis results of 13 patients diagnosed with 17OHD between 2003 and 2022 were recorded at admission and during follow-up. Whole gene next-generation sequencing was performed for the CYP17A1 gene. Multiplex ligation-dependent probe amplification was used to detect deletions in patients without point mutations in CYP17A1.

RESULTS: The median age at diagnosis was 14.0 (3.5-16.8) years. Nine of 13 (69.2%) had 46,XY karyotypes. All patients were phenotypically female and were raised as girls. The most common reasons for admission were the absence of puberty and amenorrhea (n=8, 61.5%), followed by hypertension (n=3, 23.0%) and family screening (n=2, 15.3%). At the time of diagnosis, hypertension was detected in 10 (76.9%) patients, and 11 (84.6%) patients had hypokalemia.

CONCLUSIONS: 17OHD should be considered in patients with pubertal delay/primary amenorrhea, hypertension, and hypokalemia. Adrenal function should be included in the clinical study of hypergonadotropic hypogonadism, after excluding Turner syndrome, in all 46,XX females. Deletion in the CYP17A1, including exons 1-6, is the founder mutation for Turkey's East and Southeast regions.