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This version published online on January 9, 2007
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2006-2490
A more recent version of this article appeared on April 1, 2007
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Submitted on November 13, 2006
Accepted on January 2, 2007

Prevalence of permanent neonatal diabetes in Slovakia and successful replacement of insulin with sulfonylurea therapy in KCNJ11 and ABCC8 mutation carriers

Juraj Stanik MD, Daniela Gasperikova PhD, Magdalena Paskova MD, Lubomir Barak MD, PhD, Jana Javorkova MD, Emilia Jancova MD, Miriam Ciljakova MD, Peter Hlava MD, Jozef Michalek MD, PhD, Sarah E. Flanagan BSc, Ewan Pearson MRCP, PhD, Andrew T. Hattersley FRCP, DM, Sian Ellard MRCPath, PhD, and Iwar Klimes MD, DSc*

DIABGENE and the Diabetes Research Laboratory, Institute of Experimental Endocrinology, Bratislava, Slovakia, Children Diabetes Center at the First Department of Pediatrics, Comenius University Medical School, Bratislava, Slovakia, Second Department of Pediatrics, Safarik University Medical School, Kosice, Slovakia, Department of Pediatrics, Jessenius Faculty Medicine, Comenius University, Martin, Slovakia, National Health Registries Division, National Health Information Center, Bratislava, Slovakia, National Institute for Diabetes and Endocrinology, Lubochna, Slovakia, Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, United Kingdom, Ninewells Hospital, Medical School, Dundee, United Kingdom

* To whom correspondence should be addressed. E-mail: iwar.klimes{at}savba.sk.

Context: Mutations in the KCNJ11 and ABCC8 genes encoding the pancreatic beta cell KATP channel have recently been shown to be the most common cause of permanent neonatal diabetes mellitus (PNDM). Information regarding the frequency of PNDM has been based mainly on non-population or short-term collections only. Thus, the aim of this study was to identify the incidence of PNDM in Slovakia and to switch patients to sulfonylurea (SU) where applicable.

Design: We searched for PNDM patients in the Slovak Children Diabetes Registry. In insulin treated patients who matched the clinical criteria for PNDM, the KCNJ11 or ABCC8 genes were sequenced, and mutation carriers were invited for replacement of insulin with SU.

Results: Eight patients with diabetes onset before the 6th month of life without remission were identified since 1981, what corresponds to the PNDM incidence in Slovakia one case in 215,417 live births. In four patients, 3 different KCNJ11 mutations were found (R201H, H46Y and L164P). Three patients with the KCNJ11 mutations (R201H and H46Y) were switched from insulin to SU, decreasing their HbA1c from 9.3-11.0% on insulin to 5.7-6.6% on SU treatment. One patient has a novel V86A mutation in the ABCC8 gene, and was also substituted with SU.

Conclusions: PNDM frequency in Slovakia is much higher (1 in 215,417 live births) than previously suggested from international estimates (about 1 in 800,000). We identified one ABCC8 and 4 KCNJ11 mutation carriers, of whom 4 were successfully transferred to SU, dramatically improving their diabetes control and quality of life.
Key words: Permanent Neonatal Diabetes • incidence • KCNJ11 • ABCC8 • sulfonylurea




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