Glibenclamide unresponsiveness in a Brazilian child with permanent neonatal diabetes mellitus and DEND syndrome due to a C166Y mutation in KCNJ11 (Kir6.2) gene.
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.
Della Manna
Thais
T
Instituto da Criança, Hospital das Clínicas, Universidade de São Paulo, SP, Brasil. thais.manna@icr.usp.br
Battistim
Claudilene
C
Radonsky
Vanessa
V
Savoldelli
Roberta D
RD
Damiani
Durval
D
Kok
Fernando
F
Pearson
Ewan R
ER
Ellard
Sian
S
Hattersley
Andrew T
AT
Reis
André F
AF
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
D005905:Glyburide; D007004:Hypoglycemic Agents; D024661:Potassium Channels, Inwardly Rectifying; D000099161:Kcnj11 Channel