Glibenclamide Unresponsiveness in a Brazilian Child with Permanent Neonatal Diabetes Mellitus and DEND Syndrome Due to a C166Y Mutation in KCNJ11 (Kir6.2) Gene

Thais Della Manna, Claudilene Batristim, Vanessa Radonsky, Roberta D. Savoldelli, Durval Damiani, Fernando Kok, Ewan R. Pearson, Sian Ellard, Andrew T. Hattersley, Andre F. Reis

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    18 Citations (Scopus)

    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. (Arq Bras Endocrinol Metab 2008; 52/8:1350-1355)

    Original languageEnglish
    Pages (from-to)1350-1355
    Number of pages6
    JournalArquivos Brasileiros de Endocrinologia e Metabologia
    Volume52
    Issue number8
    Publication statusPublished - Nov 2008

    Keywords

    • Neonatal diabetes mellitus
    • KATP channels
    • KCNJ11
    • C166Y mutation
    • Glibenclamide
    • Treatment failure
    • SULFONYLUREA THERAPY
    • ACTIVATING MUTATIONS
    • DEVELOPMENTAL DELAY
    • NEUROLOGICAL FEATURES
    • MOLECULAR-BASIS
    • ENCODES KIR6.2
    • COMMON-CAUSE
    • ATP
    • EPILEPSY
    • INSULIN

    Cite this

    Della Manna, T., Batristim, C., Radonsky, V., Savoldelli, R. D., Damiani, D., Kok, F., Pearson, E. R., Ellard, S., Hattersley, A. T., & Reis, A. F. (2008). Glibenclamide Unresponsiveness in a Brazilian Child with Permanent Neonatal Diabetes Mellitus and DEND Syndrome Due to a C166Y Mutation in KCNJ11 (Kir6.2) Gene. Arquivos Brasileiros de Endocrinologia e Metabologia, 52(8), 1350-1355.