BCKDK gene

Also known as: Autism-epilepsy syndrome due to branched chain ketoacid dehydrogenase kinase deficiency; BCKDK deficiency (BCKDKD).

(OMIM#614923 https://omim.org/entry/614923)

1. The disease:

A rare disorder of branched-chain amino acid metabolism characterized by childhood-onset epilepsy, autism and intellectual disability with reduced levels of plasma branched chain aminoacids.

2. The symptoms:

BCKDKD can have a variable clinical picture with seizures in the first year of age or with ASD in adulthood. The classical presentation is autism, epilepsy, intellectual disability and reduced branched-chain amino acids (BCAAs). Normally, the seizures are the first symptom to appear. Lack of early signs or symptoms does not exclude the diagnosis.

3. Actions to take in case of early diagnosis

  • Infants with a positive genetic test (having 2 pathogenic variants or 2 copies of a single pathogenic variant in the gene BCKDK) should continue breastfeeding and avoid baby formulas. Early treatment is essential in preventing chronic symptoms.
  • Biochemical correlation is essential for confirming diagnosis with plasma or CSF quantitative amino acid. Biochemical NBS with tandem mass spectrometry can also help (if you inform the NBS that you will need low cutoffs for BCAAs).
  • BCKDKD is a lifelong disease that requires lifetime management and regular follow-up with a metabolic physician and dietician, a part from a multidisciplinary approach to care.
  • Genetic counseling is highly recommended for family planning and evaluation of at-risk family members such as siblings.

4. More information

Orphanet: https://www.orpha.net/consor/cgi-bin/Disease_Search.php?lng=EN&data_id=21310&Disease_Disease_Search_diseaseGroup=Branched-chain-keto-acid-dehydrogenase-kinase-deficiency&Disease_Disease_Search_diseaseType=Pat&Disease(s)/group%20of%20diseases =Syndrome-d’épilepsie-autistique-due-à-une-chaîne-ramifiée-cétoacide-déshydrogénase-kinase-déficience&title=Autisme-épilepsie%20syndrome%20due%20à%20branched%20chain%20ketoacid%20dehydrogenase%20kinase%20deficiency&search=Disease_Search_Simple


  • Novarino G, El-Fishawy P, Kayserili H, et al. Mutations in BCKD-kinase lead to a potentially treatable form of autism with epilepsy. 2012;338(6105):394-397. doi:10.1126/science.1224631. PMID: 22956686.
  • García-Cazorla A, Oyarzabal A, Fort J, et al. Two novel mutations in the BCKDK (branched-chain keto-acid dehydrogenase kinase) gene are responsible for a neurobehavioral deficit in two pediatric unrelated patients. Hum Mutat. 2014;35(4):470-477. doi:10.1002/humu.22513. PMID: 24449431.