TY - JOUR
T1 - Sulfonylurea improves CNS function in a case of intermediate DEND syndrome caused by a mutation in KCNJ11
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 - 2007/11/1
Y1 - 2007/11/1
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 (KATP) 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 KATP 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 (KATP) 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 KATP 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.
UR - http://www.scopus.com/inward/record.url?scp=35748967277&partnerID=8YFLogxK
U2 - 10.1038/ncpneuro0640
DO - 10.1038/ncpneuro0640
M3 - Article
C2 - 17982434
AN - SCOPUS:35748967277
SN - 1745-834X
VL - 3
SP - 640
EP - 645
JO - Nature Clinical Practice Neurology
JF - Nature Clinical Practice Neurology
IS - 11
ER -
