Real-world insights into neurodevelopmental outcomes amongst people with congenital hyperinsulinism

Orphanet J Rare Dis. 2026 Jul 3. doi: 10.1186/s13023-026-04471-7. Online ahead of print.

ABSTRACT

BACKGROUND: Congenital hyperinsulinism (HI) is a rare condition causing excessive insulin secretion, leading to severe hypoglycemia and high risk of neurological damage. Studies of neurodevelopmental outcomes in HI report prevalence ranging from less than one-quarter to about half of all people with HI. These studies largely focus on formal clinical assessments, but the real-world experiences of individuals with HI and their families are rarely published. The aim of this study was to describe the neurodevelopmental outcomes of a heterogenous cohort of individuals with HI directly from the perspective of the person with HI or their family, as shared through the HI Global Registry.

RESULTS: 193 participants with HI from 34 countries were included in this analysis. Mean age at follow-up was 12.52 years (SD = 12.60). 66% of all participants, and 72% of participants aged ≥ 5 years at follow-up (n = 145), reported an adverse neurodevelopmental outcome. Of those aged ≥ 5 years at follow-up, 50% reported a diagnosed neurological, neurodevelopmental, or sensory disorder, 57% reported a history of developmental delay, and 18% reported a diagnosed mental health condition. Amongst participants ≥ 5 years of age with an adverse neurodevelopmental outcome, approximately half were capable of performing at peer level in domains of daily life. Participants added richness to the categorical data by providing free-text responses describing the problems faced in day-to-day life, with reported challenges in social, emotional, and behavioral issues.

CONCLUSIONS: This is the first study of neurodevelopmental outcomes in people with HI to focus on real-world data reported directly from people with HI and their families. Neurodevelopmental challenges were highly prevalent in people with HI and extended beyond formal clinical diagnoses into social, emotional, and behavioral problems. Proactive developmental assessments should be offered to all children with HI, and efforts should be made to develop multidisciplinary teams to support all medical and developmental aspects of care for people with HI. The real-world data on neurodevelopmental outcomes and experiences of individuals with HI and their families generated in this study will serve as a benchmark and help to quantify how future advances in diagnosis and treatment impact patient-centered neurodevelopmental outcomes.

PMID:42399951 | DOI:10.1186/s13023-026-04471-7