Sulfonylurea improves CNS function in a case of intermediate DEND syndrome caused by a mutation in KCNJ11

Wojciech Mlynarski; Andrei I Tarasov; Agnieszka Gach; Christophe A Girard; Iwona Pietrzak; Lejla Zubcevic; Jacek Kusmierek; Tomasz Klupa; Maciej T Malecki; Frances M Ashcroft

doi:10.1038/ncpneuro0640

Sulfonylurea improves CNS function in a case of intermediate DEND syndrome caused by a mutation in KCNJ11

Wojciech Mlynarski
, Andrei I Tarasov
, Agnieszka Gach
, Christophe A Girard
, Iwona Pietrzak
, Lejla Zubcevic
, Jacek Kusmierek
, Tomasz Klupa
, Maciej T Malecki
, Frances M Ashcroft

Research output: Contribution to journal › Article › peer-review

103 Citations (Scopus)

Abstract

BACKGROUND: A 12-week-old female presented with neonatal diabetes. Insulin therapy alleviated the diabetes, but the patient showed marked motor and mental developmental delay. The patient underwent genetic evaluation at the age of 6 years, prompted by reports that mutations in the KCNJ11 gene caused neonatal diabetes.

INVESTIGATIONS: Genomic sequencing of the ATP-sensitive potassium (K(ATP)) channel gene KCNJ11 and in vitro functional analysis of the channel defect, and single-photon emission CT imaging before and after glibenclamide therapy.

DIAGNOSIS: Genetic evaluation revealed a missense mutation (His46Leu) in KCNJ11, which encodes the Kir6.2 subunit of the K(ATP) channel, conferring reduced ATP sensitivity. Functional studies demonstrated that the mutant channels were strongly inhibited by the sulfonylurea tolbutamide.

MANAGEMENT: Sulfonylurea (glibenclamide) treatment led to both improved glucose homeostasis and an increase in mental and motor function.

Original language	English
Pages (from-to)	640-5
Number of pages	6
Journal	Nature Reviews Neurology
Volume	3
Issue number	11
DOIs	https://doi.org/10.1038/ncpneuro0640
Publication status	Published - Nov 2007

Keywords

Child
Child, Preschool
DNA Mutational Analysis
Developmental Disabilities/drug therapy
Diabetes Mellitus/drug therapy
Female
Gait Disorders, Neurologic/drug therapy
Glyburide/therapeutic use
Humans
Hypoglycemic Agents/therapeutic use
Infant
Insulin/therapeutic use
Mutation, Missense
Potassium Channels, Inwardly Rectifying/genetics
Sulfonylurea Compounds/therapeutic use
Tomography, Emission-Computed, Single-Photon

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title = "Sulfonylurea improves CNS function in a case of intermediate DEND syndrome caused by a mutation in KCNJ11",

abstract = "BACKGROUND: A 12-week-old female presented with neonatal diabetes. Insulin therapy alleviated the diabetes, but the patient showed marked motor and mental developmental delay. The patient underwent genetic evaluation at the age of 6 years, prompted by reports that mutations in the KCNJ11 gene caused neonatal diabetes.INVESTIGATIONS: Genomic sequencing of the ATP-sensitive potassium (K(ATP)) channel gene KCNJ11 and in vitro functional analysis of the channel defect, and single-photon emission CT imaging before and after glibenclamide therapy.DIAGNOSIS: Genetic evaluation revealed a missense mutation (His46Leu) in KCNJ11, which encodes the Kir6.2 subunit of the K(ATP) channel, conferring reduced ATP sensitivity. Functional studies demonstrated that the mutant channels were strongly inhibited by the sulfonylurea tolbutamide.MANAGEMENT: Sulfonylurea (glibenclamide) treatment led to both improved glucose homeostasis and an increase in mental and motor function.",

keywords = "Child, Child, Preschool, DNA Mutational Analysis, Developmental Disabilities/drug therapy, Diabetes Mellitus/drug therapy, Female, Gait Disorders, Neurologic/drug therapy, Glyburide/therapeutic use, Humans, Hypoglycemic Agents/therapeutic use, Infant, Insulin/therapeutic use, Mutation, Missense, Potassium Channels, Inwardly Rectifying/genetics, Sulfonylurea Compounds/therapeutic use, Tomography, Emission-Computed, Single-Photon",

author = "Wojciech Mlynarski and Tarasov, \{Andrei I\} and Agnieszka Gach and Girard, \{Christophe A\} and Iwona Pietrzak and Lejla Zubcevic and Jacek Kusmierek and Tomasz Klupa and Malecki, \{Maciej T\} and Ashcroft, \{Frances M\}",

year = "2007",

month = nov,

doi = "10.1038/ncpneuro0640",

language = "English",

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pages = "640--5",

journal = "Nature Reviews Neurology",

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AU - Mlynarski, Wojciech

AU - Tarasov, Andrei I

AU - Gach, Agnieszka

AU - Girard, Christophe A

AU - Pietrzak, Iwona

AU - Zubcevic, Lejla

AU - Kusmierek, Jacek

AU - Klupa, Tomasz

AU - Malecki, Maciej T

AU - Ashcroft, Frances M

PY - 2007/11

Y1 - 2007/11

N2 - BACKGROUND: A 12-week-old female presented with neonatal diabetes. Insulin therapy alleviated the diabetes, but the patient showed marked motor and mental developmental delay. The patient underwent genetic evaluation at the age of 6 years, prompted by reports that mutations in the KCNJ11 gene caused neonatal diabetes.INVESTIGATIONS: Genomic sequencing of the ATP-sensitive potassium (K(ATP)) channel gene KCNJ11 and in vitro functional analysis of the channel defect, and single-photon emission CT imaging before and after glibenclamide therapy.DIAGNOSIS: Genetic evaluation revealed a missense mutation (His46Leu) in KCNJ11, which encodes the Kir6.2 subunit of the K(ATP) channel, conferring reduced ATP sensitivity. Functional studies demonstrated that the mutant channels were strongly inhibited by the sulfonylurea tolbutamide.MANAGEMENT: Sulfonylurea (glibenclamide) treatment led to both improved glucose homeostasis and an increase in mental and motor function.

AB - BACKGROUND: A 12-week-old female presented with neonatal diabetes. Insulin therapy alleviated the diabetes, but the patient showed marked motor and mental developmental delay. The patient underwent genetic evaluation at the age of 6 years, prompted by reports that mutations in the KCNJ11 gene caused neonatal diabetes.INVESTIGATIONS: Genomic sequencing of the ATP-sensitive potassium (K(ATP)) channel gene KCNJ11 and in vitro functional analysis of the channel defect, and single-photon emission CT imaging before and after glibenclamide therapy.DIAGNOSIS: Genetic evaluation revealed a missense mutation (His46Leu) in KCNJ11, which encodes the Kir6.2 subunit of the K(ATP) channel, conferring reduced ATP sensitivity. Functional studies demonstrated that the mutant channels were strongly inhibited by the sulfonylurea tolbutamide.MANAGEMENT: Sulfonylurea (glibenclamide) treatment led to both improved glucose homeostasis and an increase in mental and motor function.

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KW - Hypoglycemic Agents/therapeutic use

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KW - Potassium Channels, Inwardly Rectifying/genetics

KW - Sulfonylurea Compounds/therapeutic use

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ER -

Sulfonylurea improves CNS function in a case of intermediate DEND syndrome caused by a mutation in KCNJ11

Abstract

Keywords

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