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dc.contributor.authorHopkins, J. J.
dc.contributor.authorChilds, A. J.
dc.contributor.authorHoughton, J. A.
dc.contributor.authorHewat, T. I.
dc.contributor.authorAtapattu, N.
dc.contributor.authorJohnson, M. B.
dc.contributor.authorPatel, K. A.
dc.contributor.authorLaver, T. W.
dc.contributor.authorFlanagan, S. E.
dc.identifier.citationJ Clin Endocrinol Metab. 2022 Oct 14:dgac604. doi: 10.1210/clinem/dgac604.
dc.description.abstractBACKGROUND: Congenital hyperinsulinism (HI) is characterised by inappropriate insulin secretion despite low blood glucose. Persistent HI is often monogenic, with the majority of cases diagnosed in infancy. Less is known about the contribution of monogenic forms of disease in those presenting in childhood. We investigated the likelihood of finding a genetic cause in childhood-onset HI and explored potential factors leading to the later age at presentation of disease. METHODS: We screened known disease-causing genes in 1848 individuals with HI, referred for genetic testing as part of routine clinical care. Individuals were classified as infancy-onset (when diagnosed with HI <12 months) or childhood-onset (when diagnosed with HI between 1-16 years). We assessed clinical characteristics and the genotypes of individuals with monogenic HI diagnosed in childhood to gain insights into the later age at diagnosis of HI in these children. RESULTS: We identified the monogenic cause in 24% (n = 42/173) of the childhood-onset HI cohort, this was significantly lower than the proportion of genetic diagnoses in infancy-onset cases (74.5% (n = 1248/1675), P < 0.00001). 75% of individuals with genetically confirmed childhood-onset HI were diagnosed before 2.7 years suggesting these cases represent the tail-end of the normal distribution in age at diagnosis. This is supported by the finding that 81% of the variants identified in the childhood-onset cohort were detected in those diagnosed in infancy. CONCLUSION: We have shown that monogenic HI is an important cause of hyperinsulinism presenting outside of infancy. Genetic testing should be considered in children with persistent hyperinsulinism, regardless of age at diagnosis.
dc.publisherEndocrine Society
dc.rights© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.
dc.subjectgenetic testing
dc.subjectmonogenic disease
dc.titleHyperinsulinaemic hypoglycaemia diagnosed in childhood can be monogenic
dc.typeJournal Article
dc.identifier.journalThe Journal of clinical endocrinology and metabolism
dc.description.noteThe article is available via Open Access. Click on the 'Additional link' above to access the full-text.
dc.description.admin-notePublished version, accepted version (12 month embargo), submitted version

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© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.
Except where otherwise noted, this item's license is described as © The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.