Glibenclamide unresponsiveness in a Brazilian child with permanent neonatal diabetes mellitus and DEND syndrome due to a C166Y mutation in KCNJ11 (Kir6.2) gene

• Autor(a) principal: Della Manna, Thais
• Data de Publicação: 2008
• Outros Autores: Battistim, Claudilene, Radonsky, Vanessa, Savoldelli, Roberta Diaz, Damiani, Durval, Kok, Fernando, Pearson, Ewan R., Ellard, Sian, Hattersley, Andrew T., Reis, André Fernandes [UNIFESP]
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNIFESP
• Texto Completo: http://dx.doi.org/10.1590/S0004-27302008000800024; http://repositorio.unifesp.br/handle/11600/4612
• topic: Neonatal diabetes mellitus; KATP channels; KCNJ11; C166Y mutation; Glibenclamide; Treatment failure; Diabetes melito neonatal; Canais KATP; KCNJ11; Mutação C166Y; Glibenclamida; Falha de tratamento

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.