Referenced in: none

Automatically associated channels: Kir1.1 , Kir6.2

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.

Authors: Thais Della Manna, Claudilene Battistim, Vanessa Radonsky, Roberta D Savoldelli, Durval Damiani, Fernando Kok, Ewan R Pearson, Sian Ellard, Andrew T Hattersley, André F Reis

Journal, date & volume: Arq Bras Endocrinol Metabol, 2008 Nov , 52, 1350-5

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/19169493

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.