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

    Research output: Contribution to journalArticle

    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, Thais ; Batristim, Claudilene ; Radonsky, Vanessa ; Savoldelli, Roberta D. ; Damiani, Durval ; Kok, Fernando ; Pearson, Ewan R. ; Ellard, Sian ; Hattersley, Andrew T. ; Reis, Andre F. / Glibenclamide Unresponsiveness in a Brazilian Child with Permanent Neonatal Diabetes Mellitus and DEND Syndrome Due to a C166Y Mutation in KCNJ11 (Kir6.2) Gene. In: Arquivos Brasileiros de Endocrinologia e Metabologia. 2008 ; Vol. 52, No. 8. pp. 1350-1355.
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    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. (Arq Bras Endocrinol Metab 2008; 52/8:1350-1355)",
    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",
    author = "{Della Manna}, Thais and Claudilene Batristim and Vanessa Radonsky and Savoldelli, {Roberta D.} and Durval Damiani and Fernando Kok and Pearson, {Ewan R.} and Sian Ellard and Hattersley, {Andrew T.} and Reis, {Andre F.}",
    year = "2008",
    month = "11",
    language = "English",
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    journal = "Arquivos Brasileiros de Endocrinologia e Metabologia",
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    Della Manna, T, Batristim, C, Radonsky, V, Savoldelli, RD, Damiani, D, Kok, F, Pearson, ER, Ellard, S, Hattersley, AT & Reis, AF 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, vol. 52, no. 8, pp. 1350-1355.

    Glibenclamide Unresponsiveness in a Brazilian Child with Permanent Neonatal Diabetes Mellitus and DEND Syndrome Due to a C166Y Mutation in KCNJ11 (Kir6.2) Gene. / Della Manna, Thais; Batristim, Claudilene; Radonsky, Vanessa; Savoldelli, Roberta D.; Damiani, Durval; Kok, Fernando; Pearson, Ewan R.; Ellard, Sian; Hattersley, Andrew T.; Reis, Andre F.

    In: Arquivos Brasileiros de Endocrinologia e Metabologia, Vol. 52, No. 8, 11.2008, p. 1350-1355.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Glibenclamide Unresponsiveness in a Brazilian Child with Permanent Neonatal Diabetes Mellitus and DEND Syndrome Due to a C166Y Mutation in KCNJ11 (Kir6.2) Gene

    AU - Della Manna, Thais

    AU - Batristim, Claudilene

    AU - Radonsky, Vanessa

    AU - Savoldelli, Roberta D.

    AU - Damiani, Durval

    AU - Kok, Fernando

    AU - Pearson, Ewan R.

    AU - Ellard, Sian

    AU - Hattersley, Andrew T.

    AU - Reis, Andre F.

    PY - 2008/11

    Y1 - 2008/11

    N2 - 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)

    AB - 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)

    KW - Neonatal diabetes mellitus

    KW - KATP channels

    KW - KCNJ11

    KW - C166Y mutation

    KW - Glibenclamide

    KW - Treatment failure

    KW - SULFONYLUREA THERAPY

    KW - ACTIVATING MUTATIONS

    KW - DEVELOPMENTAL DELAY

    KW - NEUROLOGICAL FEATURES

    KW - MOLECULAR-BASIS

    KW - ENCODES KIR6.2

    KW - COMMON-CAUSE

    KW - ATP

    KW - EPILEPSY

    KW - INSULIN

    M3 - Article

    VL - 52

    SP - 1350

    EP - 1355

    JO - Arquivos Brasileiros de Endocrinologia e Metabologia

    JF - Arquivos Brasileiros de Endocrinologia e Metabologia

    SN - 0004-2730

    IS - 8

    ER -