Clinical characteristics and phenotype-genotype analysis in Turkish patients with congenital hyperinsulinism; predominance of recessive KATP channel mutations

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dc.contributor.authorDemirbilek, Huseyin
dc.contributor.authorArya, Ved Bhushan
dc.contributor.authorOzbek, Mehmet Nuri
dc.contributor.authorAkinci, Aysehan
dc.contributor.authorDogan, Murat
dc.contributor.authorDemirel, Fatma
dc.contributor.authorHoughton, Jayne
dc.date.accessioned2024-04-24T17:18:03Z
dc.date.available2024-04-24T17:18:03Z
dc.date.issued2014
dc.departmentDicle Üniversitesien_US
dc.description.abstractObjective: Congenital hyperinsulinism (CHI) is the commonest cause of hyperinsulinaemic hypoglycaemia in the neonatal, infancy and childhood periods. Its clinical presentation, histology and underlying molecular biology are extremely heterogeneous. The aim of this study was to describe the clinical characteristics, analyse the genotype phenotype correlations and describe the treatment outcome of Turkish CHI patients. Design and methods: A total of 35 patients with CHI were retrospectively recruited from four large paediatric endocrine centres in Turkey. Detailed clinical, biochemical and genotype information was collected. Results: Diazoxide unresponsiveness was observed in nearly half of the patients (n= 17; 48.5%). Among diazoxide-unresponsive patients, mutations in ABCC8/KCNJ11 were identified in 16 (94%) patients. Among diazoxide-responsive patients (n=18), mutations were identified in two patients (11%). Genotype phenotype correlation revealed that mutations in ABCC8/KCNJ11 were associated with an increased birth weight and early age of presentation. Five patients had p.L1171fs (c.3512de1) ABCC8 mutations, suggestive of a founder effect. The rate of detection of a pathogenic mutation was higher in consanguineous families compared with non-consanguineous families (87.5 vs 21%; P<0.0001). Among the diazoxide-unresponsive group, ten patients were medically managed with octreotide therapy and carbohydraterich feeds and six patients underwent subtotal pancreatectomy. There was a high incidence of developmental delay and cerebral palsy among diazoxide-unresponsive patients. Conclusions: This is the largest study to report genotype phenotype correlations among Turkish patients with CHI. Mutations in ABCC8 and KCNJ11 are the commonest causes of CHI in Turkish patients (48.6%). There is a higher likelihood of genetic diagnosis in patients with early age of presentation, higher birth weight and from consanguineous pedigrees.en_US
dc.description.sponsorshipEuropean Society for Paediatric Endocrinology (ESPE); Scientific and Technological Research Council of Turkey (TUBITAK); MRC [G1001821] Funding Source: UKRI; Medical Research Council [G1001821] Funding Source: researchfishen_US
dc.description.sponsorshipH Demirbilek was funded by the European Society for Paediatric Endocrinology (ESPE) and The Scientific and Technological Research Council of Turkey (TUBITAK) during his 1-year clinical fellowship at University College London (UCL) Institute of Child Health, Great Ormond Street Hospital for Children NHS Trust, Department of Paediatric Endocrinology.en_US
dc.identifier.doi10.1530/EJE-14-0045
dc.identifier.endpage892en_US
dc.identifier.issn0804-4643
dc.identifier.issn1479-683X
dc.identifier.issue6en_US
dc.identifier.pmid24686051
dc.identifier.scopus2-s2.0-84902593763
dc.identifier.scopusqualityQ1
dc.identifier.startpage885en_US
dc.identifier.urihttps://doi.org/10.1530/EJE-14-0045
dc.identifier.urihttps://hdl.handle.net/11468/18572
dc.identifier.volume170en_US
dc.identifier.wosWOS:000337895700014
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoenen_US
dc.publisherBioscientifica Ltden_US
dc.relation.ispartofEuropean Journal of Endocrinology
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subject[No Keyword]en_US
dc.titleClinical characteristics and phenotype-genotype analysis in Turkish patients with congenital hyperinsulinism; predominance of recessive KATP channel mutationsen_US
dc.titleClinical characteristics and phenotype-genotype analysis in Turkish patients with congenital hyperinsulinism; predominance of recessive KATP channel mutations
dc.typeArticleen_US

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