ESPE Abstracts (2019) 92 P1-306

Genotype-Phenotype Correlation and Clinical Findings in 145 Patients with Congenital Adrenal Hyperplasia: Single Centre Experience

Gizem Cilsaat1, Guven Toksoy2, Firdevs Bas3, Birsen Karaman2, Sukran Poyrazoglu3, Oya Uyguner2, Seher Basaran2, Umut Altinoglu2, Feyza Darendeliler3


1Istanbul University Istanbul Medical Faculty Department of Pediatrics, Istanbul, Turkey. 2Istanbul University Istanbul Medical Faculty Department of Medical Genetics, Istanbul, Turkey. 3Istanbul University Istanbul Medical Faculty Department of Pediatric Endocrinology, Istanbul, Turkey


Introduction: Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders of adrenal steroidogenesis.

Aim: The purpose of this study was to investigate genotype-phenotype correlation, clinical findings and long-term outcomes in patients with CAH due to 11β-hydroxylase deficiency (11β-OHD) and 21-hydroxylase deficiency (21-OHD).

Paients and methods: 145 genetically proven 21-OHD and 11β-OHD patients were included in this study.Endocrinological, clinical and molecular findings were recorded at presentation and follow-up.

Results: Out of 145 patients diagnosed with CAH,122 had(83.6%) 21OHD[66 salt wasting (SW),40 simple virilizing(SV),16 non-classic(NC)]; 23(16.4 %)had 11β-OHD. SW 21-OHD was the most common and the earliest diagnosed CAH type. Consanguinity rate was high in all groups.Due to severe virilization and late diagnosis, some of the XX patients were raised as male.Frequency of SGA was higher in SV and NC 21-OHD(P=0.048). While 29 different mutations were detected in 21 OHD, there were 12 different mutations in 11β-OHD. The most common mutation was IVS-2 not only in the all patients with 21-OHD, but also in the SW(34.7%)and SV(34.4%). Furthermore, the most common mutation in NC 21-OHD was p.V282L(34.4%) and p.Leu299Pro(25%) in 11-βOHD.Positive predictive value(PPV) for all 21-OHD patients was 78.4%. PPV in subgroups(according to enzyme activity) was 80.8% in group0 ('Null'=Enzyme activity:0%), 100% in groupA(1%), 62.5% in groupB(1-2%), and 65.2% in groupC (20-50%). There was no genotype-phenotype correlation in patients with 11-βOHD.Mean value of the difference between the adult height and the target height for those, who have reached adult height was -0.42±0.73 in SW; -0.91±1.35 in SV, - 0,14±0,94 in NC, and -0,71±1,43 in 11-βOHD. The pubertal spurt was not sufficient in classic 21-OHD. The rate of early puberty was 24.2 % in SW, 40% in SV, 18.8% in NC 21-OHD and 56.5% in 11-βOHD(P=0.003 in all groups). Frequency of testicular adrenal rest tumour (TART) was 29.4% for SW, 33.3% for SV and 40% for 11-βOHD. While the obesity rate in all subgroups of 21-OHD(32.8% in SW,33.3% in SV, 31.2% in NC) was significantly high, it was low in the 11-βOHD (5%)(P=0.010).

Conclusion: In Turkey the rate of 11-βOHD was high.The rate of mutation diversity for both 21-OHD and 11-βOHD was very high. The positive predictive value of genotype-phenotype correlation in 21-OHD was good.Detection of the frequency of mutations may be important for early diagnosis, prenatal diagnosis and treatment, and establishing a screening strategy.