Formal Neurocognitive Testing in 60 Patients with Congenital Hyperinsulinism

Abstract

Background: Congenital hyperinsulinism (CHI) is hallmarked by persistent hypoketotic hypoglycemia in infancy. In the majority of all patients, CHI is caused by mutations in the KATP channel genes ABCC8 and KCNJ11, but other genes in the insulin-regulatory pathway have also been described. Repeated episodes of hypoglycemia include an increased risk of seizures and intellectual disability. So far, controlled psychometric studies on cognitive, motor, speech, and social-emotional outcome of CHI patients are missing. Until now, neurodevelopmental long-term outcome in CHI patients has only been measured by questionnaires, self-, parental-, or caregiver-administered instruments. Methods: This is a prospective study of 60 patients (median age 3.3 years, range 3 months to 57 years): 48 with a diffuse, 9 with a focal, and 3 with an atypical histology. Neurodevelopmental outcome was assessed using standardized psychological tests and questionnaires. Results: 28 of 60 patients showed developmental delay (46.7%). 9 of 57 patients had cognitive deficits (15.8%), 7 of 26 patients had speech problems (26.9%), and 17 of 44 patients had motor problems (38.6%). In 5 of 53 patients, social-emotional problems were reported. Outcome and the underlying genetic defect were not correlated. Conclusions: Motor problems seem to be prominent in CHI patients. Despite a high incidence of developmental delay, a permanent cognitive defect was only detectable in 9 of 58 patients.

The effect of hypoglycaemia on neurocognitive outcome in children and adolescents with transient or persistent congenital hyperinsulinism

“…Although there are previous studies on general intelligence in patients with CHI, to our knowledge this is the first time that comprehensive neurocognitive functioning has been examined in this patient group. In retrospective analysis, abnormal neurodevelopment was as common in the persistent CHI (25%) and transient CHI (27%) groups as in previous studies (26%-48% in persistent CHI [4][5][6][7][8][9][10][11] and 29%-30% in transient CHI 11 ). Similarly to that previously reported, 8 the number of children in special education was significantly higher compared with the 7.5% among Finnish pupils in comprehensive school.…”

“…In retrospective analysis, abnormal neurodevelopment was as common in the persistent CHI (25%) and transient CHI (27%) groups as in previous studies (26%–48% in persistent CHI and 29%–30% in transient CHI). Similarly to that previously reported, the number of children in special education was significantly higher compared with the 7.5% among Finnish pupils in comprehensive school.…”

“…Uncontrolled, excess insulin secretion induces a severe risk for brain damage by blocking the alternative neuroprotective mechanisms against hypoglycaemia . Abnormal neurodevelopment has been reported in 26% to 48% and 29% to 30% of patients with persistent CHI and transient CHI respectively. In previous studies, patients with persistent CHI born mostly between 1950 and 2000 have performed poorer in intelligence tests; however, opposite results have also been reported in children born after the year 2000 .…”

“…Abnormal neurodevelopment has been reported in 26% to 48% and 29% to 30% of patients with persistent CHI and transient CHI respectively. In previous studies, patients with persistent CHI born mostly between 1950 and 2000 have performed poorer in intelligence tests; however, opposite results have also been reported in children born after the year 2000 . Poorer neurological outcome was especially associated with neonatal onset and delayed diagnosis or stabilization .…”

Therapies and outcomes of congenital hyperinsulinism‐induced hypoglycaemia

“…Hyperinsulinism causes not only hypoglycaemia, but also suppresses lipolysis and reduces ketones, which act as alternative fuels to maintain brain neuronal function; therefore, hypoglycaemia caused by CHI is detrimental to the brain, with adverse neurodevelopment in a third to half of children with CHI [5][6][7][8][9].…”