A Rare Cause of Congenital Adrenal Hyperplasia: Clinical and Genetic Findings and Follow-up Characteristics of Six Patients with 17-Hydroxylase Deficiency Including Two Novel Mutations

• Published in: Journal of clinical research in pediatric endocrinology 2018-09, Vol.10 (3), p.206-215
• Main Authors: Kardelen, Aslı Derya, Toksoy, Güven, Baş, Firdevs, Yavaş Abalı, Zehra, Gençay, Genco, Poyrazoğlu, Şükran, Bundak, Rüveyde, Altunoğlu, Umut, Avcı, Şahin, Najaflı, Adam, Uyguner, Oya, Karaman, Birsen, Başaran, Seher, Darendeliler, Feyza
• Format: Article
• Language: English
• Subjects: Adrenal glands; Amenorrhea; Analysis; Blood pressure; Care and treatment; Congenital adrenal hyperplasia; Congenital diseases; Cytochrome; Enzymes; Females; Gene mutation; Genetic aspects; Genotype & phenotype; Hair; Hormones; Hyperplasia; Hypertension; Mutation; Original; Pediatrics; Protein expression; Puberty; Risk factors; Tıp; Treatment outcome
• ISSN: 1308-5727; 1308-5735
• DOI: 10.4274/jcrpe.0032

17α-hydroxylase/17,20 lyase deficiency (17OHD) is a rare form of congenital adrenal hyperplasia (CAH), characterized by hypertension and varying degrees of ambiguous genitalia and delayed puberty. The disease is associated with bi-allelic mutations in the gene located on chromosome 10q24.3. We aimed to present clinical and genetic findings and follow-up and treatment outcomes of 17OHD patients. We evaluated six patients with 17OHD from five families at presentation and at follow up. Standard deviation score of all auxological measurements was calculated according to national data and karyotype status. gene sequence alterations were investigated in all patients. The mean (±standard deviation) age of patients at presentation and follow-up time was 14.6±4.2 and 5.0±2.7 years respectively. Five patients were referred to us because of delayed puberty and primary amenorrhea and four for hypertension. One novel single nucleotide insertion leading to frame shift and another novel variant occurring at an ultra rare position, leading to a missense change, are reported, both of which caused 17OHD deficiency. Steroid replacement was started. The three patients with 46,XY karyotype who were raised as females underwent gonadectomy. Osteoporosis was detected in five patients. Four patients needed antihypertensive treatment. Improvement in osteoporosis was noted with gonadal steroid replacement and supportive therapy. 17OHD, a rare cause of CAH, should be kept in mind in patients with pubertal delay and/or hypertension. Patients with 46,XY who are raised as females require gonadectomy. Due to late diagnosis, psychological problems, gender selection, hypertension and osteoporosis are important health problems affecting a high proportion of these patients.