title: Prevalence of permanent neonatal diabetes in Slovakia and successful replacement of insulin with sulfonylurea therapy in KCNJ11 and ABCC8 mutation carriers.
abstract: BACKGROUND
  Mutations in the KCNJ11 and ABCC8 genes encoding the pancreatic beta-cell K(ATP) 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 nonpopulation 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.
  
  
  METHODS
  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 sixth month of life without remission were identified since 1981, which corresponds to the PNDM incidence in Slovakia of one case in 215,417 live births. In four patients, three 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 glycosylated hemoglobin 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 (one in 215,417 live births) than previously suggested from international estimates (about one in 800,000). We identified one ABCC8 and four KCNJ11 mutation carriers, of whom four were successfully transferred to SU, dramatically improving their diabetes control and quality of life.
authors.affiliation: DIABGENE and Diabetes Research Laboratory, Institute of Experimental Endocrinology, Slovak Academy of Sciences, Vlarska 3, SK 833 06 Bratislava, Slovak Republic.
authors.forename: Juraj
authors.initials: J
authors.lastname: Stanik
authors.forename: Daniela
authors.initials: D
authors.lastname: Gasperikova
authors.forename: Magdalena
authors.initials: M
authors.lastname: Paskova
authors.forename: Lubomir
authors.initials: L
authors.lastname: Barak
authors.forename: Jana
authors.initials: J
authors.lastname: Javorkova
authors.forename: Emilia
authors.initials: E
authors.lastname: Jancova
authors.forename: Miriam
authors.initials: M
authors.lastname: Ciljakova
authors.forename: Peter
authors.initials: P
authors.lastname: Hlava
authors.forename: Jozef
authors.initials: J
authors.lastname: Michalek
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Flanagan
authors.forename: Ewan
authors.initials: E
authors.lastname: Pearson
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Hattersley
authors.forename: Sian
authors.initials: S
authors.lastname: Ellard
authors.forename: Iwar
authors.initials: I
authors.lastname: Klimes
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D003920:Diabetes Mellitus / Q000151:congenital* / Q000188:drug therapy* / Q000453:epidemiology; D005260:Female; D006580:Genetic Carrier Screening; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007223:Infant; D007231:Infant, Newborn; D007328:Insulin / Q000627:therapeutic use*; D008297:Male; D009154:Mutation; D015221:Potassium Channels / Q000235:genetics*; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D015995:Prevalence; D011955:Receptors, Drug / Q000235:genetics*; D018154:Slovakia; D013453:Sulfonylurea Compounds / Q000627:therapeutic use*; D064233:Sulfonylurea Receptors; D016896:Treatment Outcome; D000099161:Kcnj11 Channel
chemical_list: D018528:ATP-Binding Cassette Transporters; D007004:Hypoglycemic Agents; D007328:Insulin; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D013453:Sulfonylurea Compounds; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel