Show simple item record

dc.contributor.authorHewat, T. I.
dc.contributor.authorLaver, T. W.
dc.contributor.authorHoughton, J. A. L.
dc.contributor.authorMännistö, J. M. E.
dc.contributor.authorAlvi, S.
dc.contributor.authorBrearey, S. P.
dc.contributor.authorCody, D.
dc.contributor.authorDastamani, A.
dc.contributor.authorDe Los Santos La Torre, M.
dc.contributor.authorMurphy, N.
dc.contributor.authorRami-Merhar, B.
dc.contributor.authorWefers, B.
dc.contributor.authorHuopio, H.
dc.contributor.authorBanerjee, I.
dc.contributor.authorJohnson, M. B.
dc.contributor.authorFlanagan, S. E.
dc.date.accessioned2022-04-21T09:39:09Z
dc.date.available2022-04-21T09:39:09Z
dc.date.issued2022-03-16
dc.identifier.citationPediatr Diabetes. 2022 Mar 16. doi: 10.1111/pedi.13333.
dc.identifier.pmid35294086
dc.identifier.doi10.1111/pedi.13333
dc.identifier.urihttps://rde.dspace-express.com/handle/11287/622416
dc.description.abstractBACKGROUND: Hyperinsulinism results from inappropriate insulin secretion during hypoglycaemia. Down syndrome is causally linked to a number of endocrine disorders including Type 1 diabetes and neonatal diabetes. We noted a high number of individuals with Down syndrome referred for hyperinsulinism genetic testing, and therefore aimed to investigate whether the prevalence of Down syndrome was increased in our hyperinsulinism cohort compared to the population. METHODS: We identified individuals with Down syndrome referred for hyperinsulinism genetic testing to the Exeter Genomics Laboratory between 2008 and 2020. We sequenced the known hyperinsulinism genes in all individuals and investigated their clinical features. RESULTS: We identified 11 individuals with Down syndrome in a cohort of 2011 patients referred for genetic testing for hyperinsulinism. This represents an increased prevalence compared to the population (2.5/2011 expected vs. 11/2011 observed, p = 6.8 × 10(-5) ). A pathogenic ABCC8 mutation was identified in one of the 11 individuals. Of the remaining 10 individuals, five had non-genetic risk factors for hyperinsulinism resulting from the Down syndrome phenotype: intrauterine growth restriction, prematurity, gastric/oesophageal surgery, and asparaginase treatment for leukaemia. For five individuals no risk factors for hypoglycaemia were reported although two of these individuals had transient hyperinsulinism and one was lost to follow-up. CONCLUSIONS: Down syndrome is more common in patients with hyperinsulinism than in the population. This is likely due to an increased burden of non-genetic risk factors resulting from the Down syndrome phenotype. Down syndrome should not preclude genetic testing as coincidental monogenic hyperinsulinism and Down syndrome is possible.
dc.language.isoeng
dc.publisherWiley
dc.relation.urlhttps://doi.org/10.1111/pedi.13333
dc.rights© 2022 The Authors. Pediatric Diabetes published by John Wiley & Sons Ltd.
dc.rights.urihttp://creativecommons.org/publicdomain/zero/1.0/
dc.titleIncreased referrals for congenital hyperinsulinism genetic testing in children with trisomy 21 reflects the high burden of non-genetic risk factors in this group
dc.typeJournal Article
dc.identifier.journalPediatric diabetes
dc.description.noteThe article is available via Open Access. Click on the 'Additional link' above to access the full-text.
dc.type.versionaheadofprint
dc.description.admin-notePublished version, accepted version (12 month embargo), submitted version
dc.date.epub2022-03-17


Files in this item

FilesSizeFormatView

There are no files associated with this item.

This item appears in the following Collection(s)

Show simple item record

© 2022 The Authors. Pediatric Diabetes published by John Wiley & Sons Ltd.
Except where otherwise noted, this item's license is described as © 2022 The Authors. Pediatric Diabetes published by John Wiley & Sons Ltd.