title: Glibenclamide unresponsiveness in a Brazilian child with permanent neonatal diabetes mellitus and DEND syndrome due to a C166Y mutation in KCNJ11 (Kir6.2) gene.
abstract: Heterozygous activating mutations of KCNJ11 (Kir6.2) are the most common cause of permanent neonatal diabetes mellitus (PNDM) and several cases have been successfully treated with oral sulfonylureas. We report on the attempted transfer of insulin therapy to glibenclamide in a 4-year old child with PNDM and DEND syndrome, bearing a C166Y mutation in KCNJ11. An inpatient transition from subcutaneous NPH insulin (0.2 units/kg/d) to oral glibenclamide (1 mg/kg/d and 1.5 mg/kg/d) was performed. Glucose and C-peptide responses stimulated by oral glucose tolerance test (OGTT), hemoglobin A1c levels, the 8-point self-measured blood glucose (SMBG) profile and the frequency of hypoglycemia episodes were analyzed, before and during treatment with glibenclamide. Neither diabetes control nor neurological improvements were observed. We concluded that C166Y mutation was associated with a form of PNDM insensitive to glibenclamide.
authors.affiliation: Instituto da Criança, Hospital das Clínicas, Universidade de São Paulo, SP, Brasil. thais.manna@icr.usp.br
authors.forename: Thais
authors.initials: T
authors.lastname: Della Manna
authors.forename: Claudilene
authors.initials: C
authors.lastname: Battistim
authors.forename: Vanessa
authors.initials: V
authors.lastname: Radonsky
authors.forename: Roberta D
authors.initials: RD
authors.lastname: Savoldelli
authors.forename: Durval
authors.initials: D
authors.lastname: Damiani
authors.forename: Fernando
authors.initials: F
authors.lastname: Kok
authors.forename: Ewan R
authors.initials: ER
authors.lastname: Pearson
authors.forename: Sian
authors.initials: S
authors.lastname: Ellard
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Hattersley
authors.forename: André F
authors.initials: AF
authors.lastname: Reis
mesh_terms: D001938:Brazil; D002675:Child, Preschool; D002658:Developmental Disabilities / Q000235:genetics; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D004827:Epilepsy / Q000235:genetics*; D005260:Female; D005905:Glyburide / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D009154:Mutation; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D013577:Syndrome; D000099161:Kcnj11 Channel
chemical_list: D005905:Glyburide; D007004:Hypoglycemic Agents; D024661:Potassium Channels, Inwardly Rectifying; D000099161:Kcnj11 Channel