Mutations in BCKD-kinase lead to a potentially treatable form of autism with epilepsy

ABSTRACT: Autism is present in 1% of the population, yet treatments are extremely limited. We identified homozygous inactivating mutations in the BCKDK gene in families presenting with autism and epilepsy. The encoded branched chain ketoacid dehydrogenase kinase protein is responsible for phosphorylation-mediated inactivation of the E1-alpha subunit of branched chain ketoacid dehydrogenase, itself mutated in Maple Syrup Urine Disease (MSUD). Patients with homozygous BCKDK mutations display reductions in BCKDK mRNA and protein, E1-alpha phosphorylation and serum branched chain amino acids (BCAAs). Bckdk knockout mice show abnormal brain amino acids profiles and neurobehavioral defects, which are largely corrected by dietary BCAA supplementation. Thus autism presenting with epilepsy due to BCKDK mutat

ORGANISM(S): Mus musculus

SUBMITTER: Eric Scott 

PROVIDER: E-GEOD-39447 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress