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 journalArticlepeer-review

86 Citations (Scopus)


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 languageEnglish
Pages (from-to)640-5
Number of pages6
JournalNature Reviews Neurology
Issue number11
Publication statusPublished - Nov 2007


  • 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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