Abnormal Neurodevelopmental Outcomes are Common in Children with Transient Congenital Hyperinsulinism

Abstract

Introduction: Neuroglycopenia is recognized to be associated with abnormal neurodevelopmental outcomes in 26-44% of children with persistent congenital hyperinsulinism (P-CHI). The prevalence of abnormal neurodevelopment in transient CHI (T-CHI) is not known. We have aimed to investigate abnormal neurodevelopment and associated factors in T-CHI and P-CHI.

Materials and methods: A cohort of children with CHI (n = 67, age 2.5-5 years) was assessed at follow-up review and noted to have normal or abnormal (mild or severe) neurodevelopmental outcomes for the domains of speech and language, motor, and vision. Children were classified as P-CHI (n = 33), if they had undergone surgery or remained on medical therapy, or T-CHI (n = 34), if medical treatment for hypoglycemia was stopped.

Results: Overall, abnormal neurodevelopment was present in 26 (39%) children with CHI, of whom 18 (69%) were severe. Importantly, the incidence of abnormal neurodevelopment in T-CHI was similar to that in P-CHI (30 vs. 47% respectively, p = 0.16). The prevalence of severe abnormal neurodevelopment in speech, motor, and vision domains was similar in both T-CHI and P-CHI children. For this cohort, we found that the severity of disease [based upon maximal diazoxide dose (odds ratio 95% confidence intervals) 1.3 (1.1; 1.5), p = 0.03], and early presentation of CHI <7 days following birth [5.9 (1.3; 27.8), p = 0.02] were significantly associated with abnormal neurodevelopment. There was no significant association with gender, genotype, or the histopathological basis of CHI.

Conclusion: Abnormal neurodevelopment was evident in one third of children with both T-CHI and P-CHI, early presentation and severe CHI being risk factors. Early recognition and rapid correction of hypoglycemia are advocated to avoid abnormal neurodevelopment in children with CHI.

Keywords: congenital hyperinsulinism; developmental delay; hypoglycemia; neurodevelopment; neurological outcome; seizures; transient congenital hyperinsulinism.

Figure 1

Brain MR imaging in a 1-year-old girl with transient CHI, showing occipital lobe atrophy (OLA) and periventricular high signal intensities (PVHSI) in sagittal T2 FLAIR sequence scanning (1a) and occipital hyperintense signals (OHS) within subcortical white matter in proton density and T2 axial images, the latter being highly suggestive of hypoglycemic injury.

Figure 2

The severity of abnormal neurodevelopment in patients with CHI. Mild and severe abnormal neurodevelopment for both persistent (P-CHI) and transient CHI (T-CHI); the prevalence of severe abnormal neurodevelopment is similar in both groups, implying that early severity, but not the duration of hypoglycemia is important in determining the outcome of hypoglycemia in children with CHI.