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 CYP17A1 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. CYP17A1 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.

Klinefelter syndrome (KS) is the most common (1/500–1/1000) chromosomal disorder in males, but only 10% of cases are identified in childhood. This study aimed to review the data of children with KS to assess the age and presenting symptoms for diagnosis, clinical and laboratory findings, together with the presence of comorbidities. Twenty-three KS patients were analyzed retrospectively. Age at admission, presenting symptoms, comorbid problems, height, weight, pubertal status, biochemical findings, hormone profiles, bone mineral density and karyotype were evaluated. Molecular analysis was also conducted in patients with ambiguous genitalia. The median age of patients at presentation was 3.0 (0.04-16.3) years. Most of the cases were diagnosed prenatally (n=15, 65.2%). Other reasons for admission were scrotal hypospadias (n=3, 14.3%), undescended testis (n=2, 9.5%), short stature (n=1, 4.8%), isolated micropenis (n=1, 4.8%) and a speech disorder (n=1, 4.8%). The most frequent clinical findings were neurocognitive disorders, speech impairment, social and behavioral problems and undescended testes. All except two patients were prepubertal at admission. Most of the patients (n=20, 86.9%) showed the classic 47,XXY karyotype. Steroid 5 alpha-reductase 2 gene and androgen receptor gene mutations were detected in two of the three cases with genital ambiguity. Given the large number of underdiagnosed KS patients before adolescence, pediatricians need to be aware of the phenotypic variability of KS in childhood. Genetic analysis in KS patients may reveal mutations associated with other forms of disorders of sex development besides KS.

Turkish Directorate of Public Health introduced the first pilot screening program for congenital adrenal hyperplasia (CAH) at four cities of Turkey in 2017, and then extended the program with a slight change in screening strategy in 2018 at fourteen cities. To evaluate the performance of the extended study and update our previous outcomes. Retrospective, descriptive study. Neonates of ≥32 gestational weeks and ≥1500 gr birth weight from fourteen cities, born between May-December, 2018 were included in the study. Screening protocol included one sample two-tier testing as applied in the previous pilot study. In the first step, 17α-hydroxyprogesterone (17-OHP) was measured by fluoroimmunoassay in dried blood spots (DBS) obtained at 3-5 days of life. The cases with positive initial screening were tested by steroid profiling in DBS using a liquid chromatography-tandem mass spectrometry method to measure 17-OHP, 21-deoxycortisol (21-S), cortisol (F), 11-deoxycortisol and androstenedione as a second-tier test. The babies with a steroid ratio (21-S+17-OHP)/F of ≥0.7 (instead of previous ≥0.5 cut-off value) were referred to pediatric endocrinology clinics for diagnostic assessment. In the evaluated period, 241,083 newborns were screened. 12,321 (5.11%) required second-tier testing and 880 (0.36%) were referred for clinical assessment, twenty of whom were diagnosed with CAH (10 females, 10 males). Sixteen were diagnosed as classical 21-hydroxylase deficiency (21-OHD) CAH (12 cases with salt-wasting and 4 cases with simple virilising), four cases were identified with 11β-hydroxylase deficiency (11β-OHD) CAH. No patients with salt-wasting CAH were missed by neonatal screening (sensitivity was 100%). The incidence of classical 21-OHD and 11β-OHD in the screened population was 1:15,067 and 1:60,270, respectively. Turkish neonatal CAH screening effectively leads to the early diagnosis of 21-OHD and 11β-OHD by the use of steroid profiling as a second-tier test allowing for better care of these patients in the future.