ESPE Abstracts

Background: Congenital hyperinsulinism in infancy (CHI) is the most frequent cause of persistent hypoglycemia in infants. The most common and severe form of monogenic CHI is caused by inactivating mutations in ABCC8 and KCNJ11 genes located on chromosome 11p15.1. On the ABCC8 gene; previous studies have shown that mutations were reported to be mostly localized in exon 28. There is no sufficient research in Egyptian population about different mutations in congenital hyperinsulinism (CHI). The aim of this work was to study the prevalence as well as clinical associations of mutations in exon 28 of ABCC8 gene in a sample of Egyptian children with CHI.

Methods: A cross-sectional study was conducted on 13 patients diagnosed with CHI. Hyperinsulinism was diagnosed in cases with persistent and recurrent hypoglycemia, in the presence of an intravenous glucose infusion rate of > 8 mg/kg/min, detectable insulin, elevated C-peptide ≥ 0.5 ng/ml and suppressed ß-hydroxybutyrate <1.8mM during spontaneous or induced hypoglycemia. Clinical, biochemical, phenotypic characteristics, clinical outcomes as well as genetic testing by DNA sequencing were studied in children with CHI who were following at Diabetes, Endocrine and Metabolism Pediatric Unit, Children’s hospital, Cairo University.

Results: The mean age of patients was (13.9±13.3) months ranging from 17 days to 38 months, the majority were males (61.5%). Hypoglycemic seizures were the presenting feature in 84.6% of cases, lethargy in 61.5% of cases, poor feeding in 38.5%, and apnea in 15.4% of patients. 61.5% of patients presented by symptoms in first week of life, 15.4% presented in first 6 months, the rest presented later. Abnormal motor development was found in 46.2% of cases, abnormal mental development in 7.7%, delayed speech in 38.5%, while abnormal vision in 7.7%. Results of DNA sequencing showed that only one patient had intronic homozygous variant on intron 28 (rs1954399854), where there was G to A nucleotide substitution at nucleotide position 77550 Seventy % of patients were treated with octreotide, 15% with diazoxide (drug less available) and 15% with combination of both drugs. On treatment, 30% of cases had recurrent admission, 69.2% recurrent hypoglycemia, while 46.2% had recurrent convulsions.

Conclusion: Molecular studies for patients with CHI are important as it may provide important information regarding the histology of the disease, and the recurrence risk in future generations. It should be routinely carried out in those patients to correlate the type of mutation and specific management and prediction of remission.