A report of congenital adrenal hyperplasia due to 17α-hydroxylase deficiency in two 46,XX sisters

Congenital adrenal hyperplasia (CAH) is a group of rare orphan disorders, caused by mutations in seven different enzymes that impair cortisol biosynthesis. The 17α-hydroxylase deficiency (17OHD) is one of the less common forms of CAH, corresponding to approximately 1% of the cases, with an estimated annual incidence of 1 in 50 000 newborns. Two phenotypically female Ecuadorian sisters, both with primary amenorrhea, absence of secondary sexual characteristics, and osteoporosis. High blood pressure was present in the older sister. Hypergonadotropic hypogonadism profile was observed: decreased cortisol and dehydroepiandrosterone sulphate (DHEAS), increased adrenocorticotropic hormone (ACTH) and normal levels of 17-hydroxyprogesterone, extremely high deoxycorticosterone (DOC) levels, and a tomography showed bilateral adrenal hyperplasia in both sisters. Consanguinity was evident in their ancestors. Both sisters had a 46,XX karyotype, discarding an initial clinical suspicion of mosaic Turner Syndrome. Sequencing of the CYP17A1 gene of both sisters detected homozygosis for the variant c.1216T>C in the exon 7. The variant is a missense mutation in the CYP17A1 gene that causes 17OHD in two sisters from Loja, Ecuador. This is the first time such deficiency and mutation are described in two members of the same family in Ecuador.