Akademik Veri Yönetim Sistemi
61st Annual ESPE (ESPE 2023), The Hague, Hollanda, 21 - 23 Eylül 2023, ss.589
Objective: Congenital Hyperinsulinism(CHI) is a clinically, genetically, and histologically heterogeneous disease. Turkey is a county with highly prevalent cases of severe CHI due to the high rate of consanguinity and recessively inherited KATP gene mutations. We herein evaluated the clinical characteristics, molecular genetic analysis, and follow-up of a large nationwide cohort of CHI from Turkey.
Patients and method: This is a nationwide crossectional multicentre retrospective study. Data was collected using a proforma through a web-based data collection tool, CEED-NET for Pediatric Endocrinology. Clinical characteristics, presenting complaints, biochemical features, molecular genetic analysis, treatment strategies, and long-term follow-up outcomes for patients with CHI were collected.
Results: In total 364 patients (female:175), were recruited from tertiary pediatric endocrine centers from around the country. Mutation analysis results were available for 193 patients with a mutation catch-up rate of 91.7%. Mutations in ABCC8 gene(n=120; 62.1%) account for the vast majority of whole mutations which was followed by HADH(n=25; 12.9%), KCNJ11(n=18;9.3%) and GLUD1 gene mutations(n=6;3.1%). Heterozygous mutation in GCK gene(n=3), KMT2D gene(n=1), BWS(n=2), and chromosome 9p deletion syndrome account for the rest of the underlying genetics etiology. The median age of presentation was 2 weeks (Ranges:1 day to 16 years) which did not differ among patients with a KATP channel gene mutation and mutation-negative group(P=0.168). However, the median age of the first presentation was younger in patients with KATP channel gene mutations compared to other gene mutations (1 week vs 8 weeks; P<0.001). Besides, patients with KATP channel gene mutations had a statistically significant higher BW (<0.001). The rate of detection of a mutation was higher in diazoxide-unresponsive cases compared to those of the diazoxide-responsive group(P<0.001).
Conclusion: Recessive mutations in either of the KATP channel genes (ABCC8 and KCNJ11) or HADH genes account for more than 90% of the underlying genetic aetiology of CHI in our large nationwide cohort. In line with recent literature data, our results showed that higher BW and diazoxide unresponsiveness have predictive values in detecting KATP channel gene mutations. In addition, our data suggested that in patients presented later in life detection of non-KATP channel gene mutations might be more likely. The high catch-up rate for detection(92%) of a mutation was attributed to the high rate of consanguinity, and limited sources for genetics analysis thereby performing analysis in selected cases.