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Switching to sulphonylureas in children with iDEND syndrome caused by KCNJ11 mutations results in improved cerebellar perfusion

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Switching to sulphonylureas in children with iDEND syndrome caused by KCNJ11 mutations results in improved cerebellar perfusion

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dc.contributor.author Fendler, Wojciech pl
dc.contributor.author Pietrzak, Iwona pl
dc.contributor.author Brereton, Malissa F. pl
dc.contributor.author Lahmann, Carolina pl
dc.contributor.author Gadzicki, Mariusz pl
dc.contributor.author Bienkiewicz, Małgorzata pl
dc.contributor.author Drożdż, Izabela pl
dc.contributor.author Borowiec, Maciej pl
dc.contributor.author Małecki, Maciej [SAP20001383] pl
dc.contributor.author Ashcroft, Frances M. pl
dc.contributor.author Młynarski, Wojciech Michał pl
dc.date.accessioned 2020-01-17T07:50:18Z
dc.date.available 2020-01-17T07:50:18Z
dc.date.issued 2013 pl
dc.identifier.issn 0149-5992 pl
dc.identifier.uri https://ruj.uj.edu.pl/xmlui/handle/item/131461
dc.language eng pl
dc.rights Udzielam licencji. Uznanie autorstwa - Użycie niekomercyjne - Bez utworów zależnych 3.0 *
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/3.0/legalcode *
dc.title Switching to sulphonylureas in children with iDEND syndrome caused by KCNJ11 mutations results in improved cerebellar perfusion pl
dc.type JournalArticle pl
dc.description.physical 2311-2316 pl
dc.abstract.en OBJECTIVE - Activating mutations in the KCNJ11 gene, encoding the Kir6.2 subunit of the KATP channel, result in permanent neonatal diabetes mellitus. They also may cause neurologic symptoms such as mental retardation and motor problems (iDEND syndrome) and epilepsy (DEND syndrome). Sulphonylurea (SU) treatment is reported to alleviate both the neurologic symptoms and diabetes in such cases. The study aimed to establish the magnitude and functional basis of the effect of SUs on the neurologic phenotype in children with iDEND using neuroimaging before and after insulin replacement with glibenclamide. RESEARCH DESIGN ANDMETHODS - To localize and quantifythe effect of glibenclamide administration, we performed single-photon emission computed tomography in seven patients with different mutations in KCNJ11. In five patients, measurements before and after initiation of SU treatment were performed. RESULTS - Significant changes in single-photon emission computed tomography signal intensity after transfer to SU therapy were restricted to the cerebellum, consistent with previous data showing high Kir6.2 expression in this brain region. Cerebellar perfusion improved for both left (P = 0.006) and right (P = 0.01) hemispheres, with the mean improvement being 26.7 6 7.1% (n = 5). No patients showed deterioration of cerebellar perfusion on SU therapy. Electrophysiological studies revealed a good correlation between the magnitude of KATP channel dysfunction and the clinical phenotype; mutant channels with the greatest reduction in adenosine 59-triphosphate inhibition were associated with the most severe neurologic symptoms. CONCLUSIONS -We conclude it is likely that at least some of the beneficial effects of SU treatment on neurodevelopment in iDEND patients result from improved cerebellar perfusion. pl
dc.description.volume 36 pl
dc.description.number 8 pl
dc.description.points 45 pl
dc.identifier.doi 10.2337/dc12-2166 pl
dc.identifier.eissn 1935-5548 pl
dc.title.journal Diabetes Care pl
dc.affiliation Wydział Lekarski : Klinika Chorób Metabolicznych pl
dc.subtype Article pl
dc.rights.original CC-BY-NC-ND; inne; ostateczna wersja wydawcy; w momencie opublikowania; 0 pl
dc.identifier.project ROD UJ / OP pl
dc.tmp.cm 58717
.pointsMNiSW [2013 A]: 45


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Udzielam licencji. Uznanie autorstwa - Użycie niekomercyjne - Bez utworów zależnych 3.0 Except where otherwise noted, this item's license is described as Udzielam licencji. Uznanie autorstwa - Użycie niekomercyjne - Bez utworów zależnych 3.0