Clinical characteristics, outcome, and predictors of neurological sequelae of persistent congenital hyperinsulinism: A single tertiary center experience

Aim Congenital hyperinsulinism (CHI) is a heterogeneous disease with variable genetic etiology, histopathology, and clinical phenotype. This study aims to describe the clinical characteristics of persistent CHI and evaluate long-term neurological outcome and its risk factors in a cohort of Egyptian children. Methods Clinical, genetic, and biochemical data of 42 patients with CHI were collected. Patients were invited for neurological assessment, electroencephalogram, and magnetic resonance imaging of the brain. Results ABCC8 mutation was found in (61%) of cases who underwent genetic testing (17/28). Five cases with homozygous biparental ABCC8 mutation responded to combined diazoxide and octreotide without needing surgery. Seven out of twenty-one patients who had pancreatectomy (33%) developed diabetes after a median period of 4.8 (range:1-10) years following surgery. Fifty-five percent of our patients had neurodevelopmental impairment at follow-up. Logistic regression analysis has shown that delayed referral to tertiary centre for more than 8 days, delayed diagnosis of CHI for more than 14 days and hospital admission for more than 30 days, are significant predictors of unfavorable neurological sequelae in CHI; (OR = 12.7 [2.56], p = 0.001), (OR = 12.7 [2.9-56], p = 0.001), and (OR = 3.8 [0.14.5], p = 0.043), respectively. Conclusions ABCC8 mutation was the commonest genetic mutation underlying CHI in this study group. CHI cases with biparental homozygous ABCC8 mutation may show response to combined octreotide and diazoxide therapy. More than half of our patients had neurodevelopmental impairment at follow-up. Delayed referral to expert centre, delayed diagnosis and longer hospital stay are significant predictors of neurological disability in CHI cases.

Automated summary

ABCC8 mutation was the most common genetic mutation in this study, and patients with biparental homozygous ABCC8 mutation may respond to combined octreotide and diazoxide therapy. More than 50% of patients had neurodevelopmental impairment at follow-up. Delayed referral, delayed diagnosis, and longer hospital stay are significant predictors of neurological disability in CHI cases.