Autism-epilepsy syndrome due to branched chain ketoacid dehydrogenase kinase deficiency

General Information (adopted from Orphanet):

Synonyms, Signs: BCKDKD
BCKDK DEFICIENCY
Number of Symptoms 7
OrphanetNr: 308410
OMIM Id: 614923
ICD-10: E71.1
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: 0.1 of 100 000
Inheritance:
[Orphanet]
Age of onset:

Disease classification (adopted from Orphanet):

Parent Diseases: Amino acid or protein metabolism disease with epilepsy
 -Rare neurologic disease
Disorder of branched-chain amino acid metabolism
 -Rare genetic disease

Comment:

Case study with 6 patients in 3 consanguineous families identified inactivating mutations in the gene BCKDK (Branched Chain Ketoacid Dehydrogenase Kinase) . The encoded protein is responsible for phosphorylation-mediated inactivation of the E1a subunit of branched-chain ketoacid dehydrogenase (BCKDH)(PMID: 22956686). Bckdk knockout mice show abnormal brain amino acid profiles and neurobehavioral deficits that respond to dietary supplementation. Thus, autism presenting with intellectual disability and epilepsy caused by BCKDK mutations represents a potentially treatable syndrome (PMID:22956686).

Symptom Information: Sort by abundance 

1
(HPO:0001249) Intellectual disability 22956686 IBIS 1089 / 7739
2
(HPO:0000717) Autism 22956686 IBIS 108 / 7739
3
(HPO:0001250) Seizures 22956686 IBIS 1245 / 7739
4
(HPO:0001263) Global developmental delay 853 / 7739
5
(HPO:0002353) EEG abnormality 22956686 IBIS 188 / 7739
6
(HPO:0001270) Motor delay 322 / 7739
7
(HPO:0010892) Abnormality of branched chain family amino acid metabolism 22956686 IBIS 2 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Clinical Description OMIM Novarino et al. (2012) studied 3 consanguineous families with autism, epilepsy, intellectual disability, and reduced branched-chain amino acids (BCAAs). All patients were born at full term to unaffected parents. The first family (558), of Turkish origin, had 2 ...
Molecular genetics OMIM In 3 consanguineous families with autism, epilepsy, and intellectual disability, Novarino et al. (2012) detected homozygosity for mutation in the branched-chain ketoacid dehydrogenase kinase (BCKDK) gene (614901.0001-614901.0003). Two families carried null mutations (nonsense and frameshift) and 1 family ...