BCKDKD
MCID: BRN135
MIFTS: 37

Branched-Chain Keto Acid Dehydrogenase Kinase Deficiency (BCKDKD)

Categories: Genetic diseases, Metabolic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Branched-Chain Keto Acid Dehydrogenase Kinase Deficiency

MalaCards integrated aliases for Branched-Chain Keto Acid Dehydrogenase Kinase Deficiency:

Name: Branched-Chain Keto Acid Dehydrogenase Kinase Deficiency 57 12 29 6 15
Branched-Chain Ketoacid Dehydrogenase Kinase Deficiency 57 72 36 13 39 70
Bckdkd 57 12 72
Autism-Epilepsy Syndrome Due to Branched Chain Ketoacid Dehydrogenase Kinase Deficiency 12 58
Bckdk Deficiency 57 12
Brain Diseases, Metabolic, Inborn 44

Characteristics:

Orphanet epidemiological data:

58
autism-epilepsy syndrome due to branched chain ketoacid dehydrogenase kinase deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide);

Classifications:

Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism


External Ids:

Disease Ontology 12 DOID:0090126
OMIM® 57 614923
KEGG 36 H02136
ICD10 32 E71.1
ICD10 via Orphanet 33 E71.1
Orphanet 58 ORPHA308410
UMLS 70 C3554078

Summaries for Branched-Chain Keto Acid Dehydrogenase Kinase Deficiency

Disease Ontology : 12 An amino acid metabolic disorder that is characterized by autism, epilepsy, intellectual disability, and reduced levels of branched-chain amino acids that has material basis in homozygous mutation in the branched chain keto acid dehydrogenase kinase gene (BCKDK) on chromosome 16p11.

MalaCards based summary : Branched-Chain Keto Acid Dehydrogenase Kinase Deficiency, also known as branched-chain ketoacid dehydrogenase kinase deficiency, is related to maple syrup urine disease and optic atrophy 1. An important gene associated with Branched-Chain Keto Acid Dehydrogenase Kinase Deficiency is BCKDK (Branched Chain Keto Acid Dehydrogenase Kinase), and among its related pathways/superpathways are Metabolism and Viral mRNA Translation. The drugs carbamide peroxide and Ornithine have been mentioned in the context of this disorder. Affiliated tissues include brain, and related phenotypes are intellectual disability and autism

KEGG : 36 Branched-chain ketoacid dehydrogenase kinase (BCKDK) deficiency is a familial comorbid intellectual disability, autism, and epilepsy, caused by mutations in the BCKDK. Patients also showed abnormally low plasma levels of branched-chain amino acids.

UniProtKB/Swiss-Prot : 72 Branched-chain ketoacid dehydrogenase kinase deficiency: A metabolic disorder characterized by autism, epilepsy, intellectual disability, and reduced branched-chain amino acids.

More information from OMIM: 614923

Related Diseases for Branched-Chain Keto Acid Dehydrogenase Kinase Deficiency

Diseases related to Branched-Chain Keto Acid Dehydrogenase Kinase Deficiency via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 12)
# Related Disease Score Top Affiliating Genes
1 maple syrup urine disease 28.9 PPM1K DLD BCKDK BCKDHB BCKDHA
2 optic atrophy 1 10.0
3 autism 10.0
4 mitochondrial metabolism disease 10.0
5 citrullinemia, classic 9.9 TMLHE BCKDHB
6 amino acid metabolic disorder 9.9 BCKDHB BCKDHA
7 dihydrolipoamide dehydrogenase deficiency 9.9 DLD BCKDHB
8 glycine encephalopathy 9.7 DLD BCKDHB
9 intermediate maple syrup urine disease 9.7 PPM1K BCKDHB BCKDHA
10 methylmalonic acidemia 9.7 BCKDHB BCKDHA
11 organic acidemia 9.6 PPM1K BCKDK BCKDHB BCKDHA
12 propionic acidemia 9.5 TMLHE BCKDK BCKDHB BCKDHA

Graphical network of the top 20 diseases related to Branched-Chain Keto Acid Dehydrogenase Kinase Deficiency:



Diseases related to Branched-Chain Keto Acid Dehydrogenase Kinase Deficiency

Symptoms & Phenotypes for Branched-Chain Keto Acid Dehydrogenase Kinase Deficiency

Human phenotypes related to Branched-Chain Keto Acid Dehydrogenase Kinase Deficiency:

31
# Description HPO Frequency HPO Source Accession
1 intellectual disability 31 obligate (100%) HP:0001249
2 autism 31 obligate (100%) HP:0000717
3 seizure 31 obligate (100%) HP:0001250
4 abnormal circulating branched chain amino acid concentration 31 obligate (100%) HP:0010892

Clinical features from OMIM®:

614923 (Updated 05-Apr-2021)

Drugs & Therapeutics for Branched-Chain Keto Acid Dehydrogenase Kinase Deficiency

Drugs for Branched-Chain Keto Acid Dehydrogenase Kinase Deficiency (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1
carbamide peroxide Approved 124-43-6
2
Ornithine Approved, Nutraceutical 70-26-8, 3184-13-2 6262

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Augmentation of Umbilical Cord Blood Transplantation for Inherited Metabolic Diseases With Intrathecal Administration of Human Umbilical Cord Blood-Derived Oligodendrocyte-Like Cells Recruiting NCT02254863 Phase 1
2 Assessing Neural Mechanisms of Injury in Inborn Errors of Urea Metabolism Using Structural MRI, Functional MRI, and Magnetic Resonance Spectroscopy Completed NCT00472732
3 Longitudinal Study of Urea Cycle Disorders Recruiting NCT00237315

Search NIH Clinical Center for Branched-Chain Keto Acid Dehydrogenase Kinase Deficiency

Cochrane evidence based reviews: brain diseases, metabolic, inborn

Genetic Tests for Branched-Chain Keto Acid Dehydrogenase Kinase Deficiency

Genetic tests related to Branched-Chain Keto Acid Dehydrogenase Kinase Deficiency:

# Genetic test Affiliating Genes
1 Branched-Chain Keto Acid Dehydrogenase Kinase Deficiency 29 BCKDK

Anatomical Context for Branched-Chain Keto Acid Dehydrogenase Kinase Deficiency

MalaCards organs/tissues related to Branched-Chain Keto Acid Dehydrogenase Kinase Deficiency:

40
Brain

Publications for Branched-Chain Keto Acid Dehydrogenase Kinase Deficiency

Articles related to Branched-Chain Keto Acid Dehydrogenase Kinase Deficiency:

# Title Authors PMID Year
1
Mutations in BCKD-kinase lead to a potentially treatable form of autism with epilepsy. 57 6
22956686 2012
2
Impaired growth and neurological abnormalities in branched-chain alpha-keto acid dehydrogenase kinase-deficient mice. 57
16875466 2006
3
Autism spectrum disorders and inborn errors of metabolism: an update. 61
23921282 2013

Variations for Branched-Chain Keto Acid Dehydrogenase Kinase Deficiency

ClinVar genetic disease variations for Branched-Chain Keto Acid Dehydrogenase Kinase Deficiency:

6 (show all 29)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 BCKDK NM_005881.4(BCKDK):c.466C>T (p.Arg156Ter) SNV Pathogenic 39743 rs397514573 GRCh37: 16:31121568-31121568
GRCh38: 16:31110247-31110247
2 BCKDK NM_005881.4(BCKDK):c.222del (p.Met74fs) Deletion Pathogenic 39744 GRCh37: 16:31120858-31120858
GRCh38: 16:31109537-31109537
3 BCKDK NM_005881.4(BCKDK):c.671G>C (p.Arg224Pro) SNV Pathogenic 39745 rs147210405 GRCh37: 16:31122037-31122037
GRCh38: 16:31110716-31110716
4 BCKDK NM_005881.4(BCKDK):c.453C>G (p.Tyr151Ter) SNV Likely pathogenic 434505 rs369521689 GRCh37: 16:31121555-31121555
GRCh38: 16:31110234-31110234
5 overlap with 40 genes Deletion Uncertain significance 598742 GRCh37: 16:30554158-31536880
GRCh38:
6 BCKDK NM_005881.4(BCKDK):c.904A>G (p.Ile302Val) SNV Uncertain significance 193685 rs201164597 GRCh37: 16:31122679-31122679
GRCh38: 16:31111358-31111358
7 BCKDK NM_005881.4(BCKDK):c.196-8del Deletion Uncertain significance 640951 rs1596808347 GRCh37: 16:31120822-31120822
GRCh38: 16:31109501-31109501
8 BCKDK NM_005881.4(BCKDK):c.193A>G (p.Lys65Glu) SNV Uncertain significance 650837 rs1596808163 GRCh37: 16:31120737-31120737
GRCh38: 16:31109416-31109416
9 BCKDK NM_005881.4(BCKDK):c.373G>A (p.Val125Met) SNV Uncertain significance 197262 rs141282419 GRCh37: 16:31121102-31121102
GRCh38: 16:31109781-31109781
10 BCKDK NM_005881.4(BCKDK):c.793A>C (p.Ile265Leu) SNV Uncertain significance 944223 GRCh37: 16:31122488-31122488
GRCh38: 16:31111167-31111167
11 BCKDK NM_005881.4(BCKDK):c.1010A>G (p.Glu337Gly) SNV Uncertain significance 955963 GRCh37: 16:31123264-31123264
GRCh38: 16:31111943-31111943
12 BCKDK NM_005881.4(BCKDK):c.544-8C>G SNV Uncertain significance 1000745 GRCh37: 16:31121714-31121714
GRCh38: 16:31110393-31110393
13 BCKDK NM_005881.4(BCKDK):c.1131G>A (p.Ala377=) SNV Uncertain significance 1008861 GRCh37: 16:31123478-31123478
GRCh38: 16:31112157-31112157
14 BCKDK NM_005881.4(BCKDK):c.86C>T (p.Ala29Val) SNV Uncertain significance 955153 GRCh37: 16:31120630-31120630
GRCh38: 16:31109309-31109309
15 BCKDK NM_005881.4(BCKDK):c.347T>C (p.Ile116Thr) SNV Uncertain significance 969568 GRCh37: 16:31121076-31121076
GRCh38: 16:31109755-31109755
16 BCKDK NM_005881.4(BCKDK):c.851C>T (p.Thr284Ile) SNV Uncertain significance 846730 GRCh37: 16:31122626-31122626
GRCh38: 16:31111305-31111305
17 BCKDK NM_005881.4(BCKDK):c.847G>A (p.Ala283Thr) SNV Uncertain significance 193684 rs760851100 GRCh37: 16:31122622-31122622
GRCh38: 16:31111301-31111301
18 BCKDK NM_005881.4(BCKDK):c.305T>C (p.Ile102Thr) SNV Uncertain significance 1028955 GRCh37: 16:31121034-31121034
GRCh38: 16:31109713-31109713
19 BCKDK NM_005881.4(BCKDK):c.846-3T>A SNV Uncertain significance 166745 rs118042732 GRCh37: 16:31122618-31122618
GRCh38: 16:31111297-31111297
20 BCKDK NM_005881.4(BCKDK):c.556G>A (p.Val186Ile) SNV Uncertain significance 1037546 GRCh37: 16:31121734-31121734
GRCh38: 16:31110413-31110413
21 BCKDK NM_005881.4(BCKDK):c.936-10A>G SNV Likely benign 720197 rs374677650 GRCh37: 16:31123180-31123180
GRCh38: 16:31111859-31111859
22 BCKDK NM_005881.4(BCKDK):c.372C>T (p.His124=) SNV Likely benign 756783 rs148112682 GRCh37: 16:31121101-31121101
GRCh38: 16:31109780-31109780
23 BCKDK NM_005881.4(BCKDK):c.588G>A (p.Ser196=) SNV Likely benign 779622 rs150773521 GRCh37: 16:31121766-31121766
GRCh38: 16:31110445-31110445
24 BCKDK NM_005881.4(BCKDK):c.717-5C>T SNV Likely benign 784538 rs1291981908 GRCh37: 16:31122407-31122407
GRCh38: 16:31111086-31111086
25 BCKDK NM_005881.4(BCKDK):c.1218G>A (p.Arg406=) SNV Likely benign 194067 rs145180240 GRCh37: 16:31123565-31123565
GRCh38: 16:31112244-31112244
26 BCKDK NM_005881.4(BCKDK):c.721C>T (p.Leu241=) SNV Likely benign 502258 rs374121679 GRCh37: 16:31122416-31122416
GRCh38: 16:31111095-31111095
27 BCKDK NM_005881.4(BCKDK):c.1066A>T (p.Ser356Cys) SNV Benign 289834 rs142542453 GRCh37: 16:31123320-31123320
GRCh38: 16:31111999-31111999
28 BCKDK NM_005881.4(BCKDK):c.845+10C>T SNV Benign 128522 rs74015068 GRCh37: 16:31122550-31122550
GRCh38: 16:31111229-31111229
29 BCKDK NM_005881.4(BCKDK):c.181G>T (p.Ala61Ser) SNV Benign 783737 rs73530211 GRCh37: 16:31120725-31120725
GRCh38: 16:31109404-31109404

UniProtKB/Swiss-Prot genetic disease variations for Branched-Chain Keto Acid Dehydrogenase Kinase Deficiency:

72
# Symbol AA change Variation ID SNP ID
1 BCKDK p.Arg224Pro VAR_069037 rs147210405
2 BCKDK p.Arg174Gly VAR_072184
3 BCKDK p.Leu389Pro VAR_072185

Expression for Branched-Chain Keto Acid Dehydrogenase Kinase Deficiency

Search GEO for disease gene expression data for Branched-Chain Keto Acid Dehydrogenase Kinase Deficiency.

Pathways for Branched-Chain Keto Acid Dehydrogenase Kinase Deficiency

Pathways related to Branched-Chain Keto Acid Dehydrogenase Kinase Deficiency according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.56 TMLHE PPM1K DLD CACNA2D2 BCKDK BCKDHB
2
Show member pathways
13.32 TMLHE PPM1K DLD BCKDK BCKDHB BCKDHA
3 11.23 TMLHE DLD
4
Show member pathways
11.17 TMLHE PPM1K DLD BCKDK BCKDHB BCKDHA
5
Show member pathways
11.04 DLD BCKDHB BCKDHA
6 10.96 DLD BCKDHB BCKDHA
7
Show member pathways
10.79 DLD BCKDHB BCKDHA
8 9.91 DLD BCKDHB BCKDHA

GO Terms for Branched-Chain Keto Acid Dehydrogenase Kinase Deficiency

Cellular components related to Branched-Chain Keto Acid Dehydrogenase Kinase Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 9.63 TMLHE PPM1K DLD BCKDK BCKDHB BCKDHA
2 mitochondrial matrix GO:0005759 9.43 TMLHE PPM1K DLD BCKDK BCKDHB BCKDHA
3 mitochondrial alpha-ketoglutarate dehydrogenase complex GO:0005947 8.8 BCKDK BCKDHB BCKDHA

Biological processes related to Branched-Chain Keto Acid Dehydrogenase Kinase Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 oxidation-reduction process GO:0055114 9.26 TMLHE DLD BCKDHB BCKDHA
2 branched-chain amino acid catabolic process GO:0009083 9.02 PPM1K DLD BCKDK BCKDHB BCKDHA

Molecular functions related to Branched-Chain Keto Acid Dehydrogenase Kinase Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 oxidoreductase activity GO:0016491 9.46 TMLHE DLD BCKDHB BCKDHA
2 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring) activity GO:0003863 8.96 BCKDHB BCKDHA
3 alpha-ketoacid dehydrogenase activity GO:0003826 8.62 BCKDHB BCKDHA

Sources for Branched-Chain Keto Acid Dehydrogenase Kinase Deficiency

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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