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

Çilsaat G., Toksoy G. , Baş F. , Karaman B. , Poyrazoğlu Ş. , Uyguner Z., ...Daha Fazla

58 th Annual Meeting European Society for Paediatric Endocrinology (ESPE), Vienna, Avusturya, 20 - 22 Eylül 2019, cilt.1, no.1, ss.282

  • Cilt numarası: 1
  • Basıldığı Şehir: Vienna
  • Basıldığı Ülke: Avusturya
  • Sayfa Sayıları: ss.282


Introduction: Congenital adrenal hyperplasia (CAH) is a
group of autosomal recessive disorders of adrenal steroidogenesis.
Aim: The purpose of this study was to investigate genotypephenotype
correlation, clinical findings  and long-term outcomes
in patients with CAH due to 11-hydroxylase deficiency
(11-OHD) and 21-hydroxylase deficiency (21-OHD).
Paients and methods: 145 genetically proven 21-OHD and
11-OHD patients were included in this study.Endocrinological,
clinical and molecular findings were recorded at presentation and
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 11-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 11-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-OHD.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-OHD. 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-OHD. 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-OHD(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-OHD. 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-OHD (5%)(p=0.010).
Conclusion: In Turkey the rate of 11-OHD was high. The rate
of mutation diversity for both 21-OHD and 11-OHD was very
high. The positive predictive value of genotype-phenotype correlation
in 21-OHD was good.