title: Clinical and genetic features of Argentinian children with diabetes-onset before 12months of age: Successful transfer from insulin to oral sulfonylurea.
abstract: OBJECTIVE
  Neonatal diabetes mellitus (NDM) is a rare monogenic disorder, reported to affect less than 2 cases per 100,000 infants. There are two types, permanent (PNDM) and transient (TNDM). We describe our clinical experience in determining and comparing the genetic basis of diabetes in children with onset before 6months versus those diagnosed between 6 and 12months of age.
  
  
  METHODS
  We reviewed medical records of children with diabetes diagnosed before 12months of age. Genetic testing was performed in all cases.
  
  
  RESULTS
  12 patients were diagnosed with diabetes before 6months of age (PNDM=6; TNDM=6), and 11 patients between 6 and 12months (all with permanent diabetes). Among children with PNDM, we identified three different KCNJ11 mutations in 5 patients, and one novel ABCC8 mutation in a single patient. Among children with TNDM, we detected a KCNJ11 and ABCC8 mutation each in a single patient and methylation abnormalities at chromosome 6q24 in 4 patients. Among children with diabetes diagnosed between 6 and 12months, 1 patient had an INS mutation and one patient was homozygous for an SLC19A2 mutation which confirmed a diagnosis of thiamine-responsive megaloblastic anaemia syndrome. Five of the patients with an ABCC8 or KCNJ11 mutation have successfully transferred from insulin to glibenclamide whist 1 child demonstrated a partial response to sulfonylurea treatment.
  
  
  CONCLUSIONS
  Investigating the underlying genetic basis of diabetes in children with onset before 1year is useful for choosing the most efficient treatment, the basis of Personalized Medicine.
authors.affiliation: Section of Nutrition and Diabetes, Children's General Hospital "Dr. Pedro de Elizalde", Buenos Aires, Argentina.
authors.forename: Patricia
authors.initials: P
authors.lastname: Taberner
authors.affiliation: Institute of Biomedical and Clinical Science, University of Exeter Medical School, UK.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Flanagan
authors.affiliation: Human Genetics and Genomic Medicine, Faculty of Medicine, University of Southampton, Southampton, UK.
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Mackay
authors.affiliation: Institute of Biomedical and Clinical Science, University of Exeter Medical School, UK.
authors.forename: Sian
authors.initials: S
authors.lastname: Ellard
authors.affiliation: Division of Diabetology, Clinical Hospital "José de San Martín", University of Buenos Aires, Argentina; Institute of Cardiological Investigations "Prof. Alberto C. Taquini" (ININCA), National Research Council of Argentina (CONICET), Buenos Aires, Argentina.
authors.forename: Mariano J
authors.initials: MJ
authors.lastname: Taverna
authors.affiliation: Section of Nutrition and Diabetes, Children's General Hospital "Dr. Pedro de Elizalde", Buenos Aires, Argentina. Electronic address: mabelferrraro@yahoo.com.
authors.forename: Mabel
authors.initials: M
authors.lastname: Ferraro
mesh_terms: D000284:Administration, Oral; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D005820:Genetic Testing; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007223:Infant; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000188:drug therapy* / Q000235:genetics; D007328:Insulin / Q000008:administration & dosage* / Q000235:genetics; D008297:Male; D009154:Mutation / Q000235:genetics; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics; D013453:Sulfonylurea Compounds / Q000008:administration & dosage; D064233:Sulfonylurea Receptors / Q000235:genetics; D000099161:Kcnj11 Channel
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D024661:Potassium Channels, Inwardly Rectifying; D013453:Sulfonylurea Compounds; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel; C577507:ABCC8 protein, human
keywords: Genetics; Neonatal diabetes mellitus; Personalized Medicine; Pharmacogenetics