BSPED2013 Poster Presentations (1) (89 abstracts)
Frequency of focal and diffuse congenital hyperinsulinism with paternally inherited mutations in ABCC8 and KCNJ11
Jaya Sujatha Gopal 1 , Zainaba Mohamed 1 , Raja Padidela 1 , Leena Patel 1 , Mars Skae 1 , Mohammed Didi 1 , Jackie James 1 , Louise Caine 6 , Lindsey Rigby 2 , Karen E Cosgrove 4 , Mark Dunne 4 , Sian Ellard 5 , Indi Banerjee 1 & Peter Clayton 3
1Department of Paediatric Endocrinology, Royal Manchester Children’s Hospital, Manchester, UK; 2Department of Paediatric Endocrinology, Alder Hey Children’s NHS Foundation Trust, Liverpool, UK; 3Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK; 4Faculty of Life Sciences, University of Mancheser, Manchester, UK; 5Molecular Genetics, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK; 6Nuclear Medicine, Manchester Royal Infirmary, Manchester, UK.
Introduction: Congenital hyperinsulinism (CHI) causes severe hypoglycaemia, which can be either focal or diffuse in aetiology. Both forms are associated with paternally inherited mutations in ABCC8/KCNJ11. Lymphocytic DNA analysis alone is inadequate to diagnose focal CHI, as pancreatic maternal allelic silencing cannot be tested prior to surgery. Additional 18-fluorodopa PET–CT scanning (PET–CT) is required for definitive diagnosis; in this study, we have reviewed the diagnostic outcomes of scanning in children with paternally inherited ABCC8/KCNJ11 mutations.
Methods: The diagnosis of focal/diffuse CHI was reviewed in children with paternally inherited mutations in ABCC8/KCNJ11 (n=23) following PET–CT and confirmation by histology in those undergoing surgery. Severity of the CHI phenotype was assessed by maximum glucose requirement, maximum dose of glucagon and maximum dose of diazoxide at presentation.
Result: CHI was diagnosed with a mean (interquartile range) serum insulin 86.7 (110.2) mU/l and blood glucose 0.8 (1.4) mmol/l. The majority carried mutations in ABCC8 (n=17, 74%). Focal CHI was present in 17 (74%) children, and was successfully treated surgically. Diffuse CHI was present in 6 (26%) children where a maternal allelic mutation was not identified. In this group, only two required subtotal pancreatectomy to achieve glycaemic stability. Three children were medically managed and one child achieved spontaneous resolution. The severity phenotype did not correlate with the diagnosis of focal or diffuse CHI following PET–CT.
Conclusions: A paternally inherited mutation in ABCC8/KCNJ11 is associated with focal CHI in 74% children with CHI, requiring surgery. In those with diffuse CHI, the majority can be medically managed.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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