Examination of the relationship between genetic results and clinical findings of cases diagnosed with congenital adrenal hyperplasia

Purpose:In this study, it was aimed to evaluate the relationship between the clinical findings and genetic outcomes of children with congenital adrenal hyperplasia and the phenotype. Method: Our study is a retrospective clinical study, and the files of pediatric patients aged 0-18 years who were diagnosed with CAD in the Pediatric Endocrinology outpatient clinic of Akdeniz University Medical Faculty Hospital between 1999-2022 were reviewed. Demographic data, anthropometric measurements, clinical findings, laboratory results and mutation analysis results obtained during follow-up were collected from the files of the patients. Data were analyzed with SPSS 23 package program. Results: Of the cases (n=69), 36 (52.2%) were salt-losing, 17 (24.6%) were simple virilizing, 10 (14.5%) were non-classical and 6 (8.7%) were ) were 11-beta hydroxylase deficiency. 40 (58%) of them were bred female and 29 (42%) male. Median age of applicant; It was 0 months (0-3 months) for salt wasters, 60 months (3-132 months) for simple virilizing cases, 108.5 months (10-183 months) for nonclassical type, 29 months (0-95 months) for 11 beta hydroxylase deficiency. 21- OHE, especially the salt wasting type, was the most common and the earliest diagnosed group. The prevalence of obesity at the beginning of puberty and at the last examination was 45.4% and 38.8%, respectively. The frequency of cases who underwent genital correction operation was 34%. The frequency of central precocious puberty was 24%. 85% of the patients who reached the final adult height were below the target height. There was a history of PCOS in 15 (39%) of 38 female cases, and a history of TART in 6 (20%) of 29 male cases. The rate of consanguineous marriage was 59.4% and there was a family history in 17.4% of the cases. 45 (63.7%) of the cases had homozygous, 11 (15.9%) heterozygous, 14 (20.4%) combined heterozygous mutations. The most common IVS-2 (44.8%) mutations were observed, and the frequency of IVS-2 mutations in salt wasting and simple virilizing cases was 62.3% and 37.5%, respectively. The most common IVS2-13 C/A >G genotype was present in TK and BV types. The most common mutations in NK type are p.V281L (60%) and Q318X (13.3%), 11B (OH) ex. and 123 c.1120 C>G (72%) mutation. In simple virilizing cases, the most common IVS- 2(37.5%) mutation was followed by I172N (25%) and V281L (25%) mutations. Conclusion: In our country, where consanguineous marriage is high, the incidence of congenital adrenal hyperplasia and the diversity of mutations are high. Mutation analysis in patients diagnosed with congenital adrenal hyperplasia is important in terms of early diagnosis, prenatal diagnosis and establishing a treatment plan. In this way, deaths that may develop due to adrenal insufficiency are prevented, especially in men without suspicious genitalia. In our study, the prevalence of additional problems such as precocious puberty, PCOS, TART and obesity that developed during the follow-up of congenital adrenal hyperplasia was high. As a result, congenital adrenal hyperplasia is a serious disease due to the additional health problems it brings and the risk of loss of life due to salt loss and adrenal crisis in the early period. The prevalence of genetic studies is important in terms of providing information about the genotype-phenotype relationship and early diagnosis, treatment and prognosis of the disease, and more studies are needed on this subject Keywords: Congenital adrenal hyperplasia (CAH), 11 beta hydroxylase deficiency, 21 hydroxylase deficiency, TART (testicular adrenal rest tumor), genotype- phenotype relationship, salt waster, simple virilizing, nonclassical.