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


METHODS
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.


METHODS
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.


RESULTS
Sulfonylurea (glibenclamide) treatment led to both improved glucose homeostasis and an increase in mental and motor function.
Mlynarski
Wojciech
W
Department of Pediatrics, Medical University of Lodz, Lodz, Poland.
Tarasov
Andrei I
AI
Gach
Agnieszka
A
Girard
Christophe A
CA
Pietrzak
Iwona
I
Zubcevic
Lejla
L
Kusmierek
Jacek
J
Klupa
Tomasz
T
Malecki
Maciej T
MT
Ashcroft
Frances M
FM
D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D002658:Developmental Disabilities / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D020233:Gait Disorders, Neurologic / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D005905:Glyburide / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007223:Infant; D007328:Insulin / Q000627:therapeutic use; D020125:Mutation, Missense; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D013453:Sulfonylurea Compounds / Q000627:therapeutic use; D015899:Tomography, Emission-Computed, Single-Photon; D000099161:Kcnj11 Channel
D005905:Glyburide; D007004:Hypoglycemic Agents; D007328:Insulin; D024661:Potassium Channels, Inwardly Rectifying; D013453:Sulfonylurea Compounds; D000099161:Kcnj11 Channel