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

被引：83

作者：

Mlynarski, Woj Ciech

Tarasov, Andrei I.

Gach, Agnieszka

Girard, Christophe A.

Pietrzak, Wona

Zubcevic, Lejla

Kusmierek, Jacek

Klupa, Tornasz

Malecki, Maciej T.

Ashcroft, Frances M.

机构：

[1] Univ Oxford, Dept Physiol Anat & Genet, Oxford OX1 3PT, England

[2] Med Univ Lodz, Dept Pediat, Lodz, Poland

[3] Med Univ Lodz, Dept Mol Genet & Immunopathol, Lodz, Poland

[4] Med Univ Lodz, Dept Nucl Med, Lodz, Poland

[5] Jagiellonian Univ, Coll Med, Dept Metab Dis, Krakow, Poland

来源：

NATURE CLINICAL PRACTICE NEUROLOGY | 2007年 / 3卷 / 11期

基金：

英国惠康基金;

关键词：

ATP-sensitive potassium channel; KCNJ11; neonatal diabetes; neuropathology; sulfonylurea;

D O I：

10.1038/ncpneuro0640

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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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收藏

页码：640 / 645

页数：6

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