PDHXD
MCID: PYR031
MIFTS: 40

Pyruvate Dehydrogenase E3-Binding Protein Deficiency (PDHXD)

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

Aliases & Classifications for Pyruvate Dehydrogenase E3-Binding Protein Deficiency

MalaCards integrated aliases for Pyruvate Dehydrogenase E3-Binding Protein Deficiency:

Name: Pyruvate Dehydrogenase E3-Binding Protein Deficiency 57 59 74 37 29 6 40 72
Lacticacidemia Due to Pdx1 Deficiency 57 74 13
Lactic Acidemia Due to Defect in Lipoyl-Containing Component X of the Pyruvate Dehydrogenase Complex 57 74
Lipoamide Dehydrogenase Deficiency 59 29
Pdhxd 57 74
Branched Chain Alpha-Ketoacid Dehydrogenase Complex Deficiency 59
Pyruvate Dehydrogenase Complex Component E3 Deficiency 59
Pyruvate Dehydrogenase Protein X Component Deficiency 59
Glycine Cleavage System L Protein Deficiency 59
Nadh Cytochrome B5 Reductase Deficiency 72
Dihydrolipoyl Dehydrogenase Deficiency 59
2-Oxoglutarate Complex Deficiency 59
Diaphorase Deficiency 59

Characteristics:

Orphanet epidemiological data:

59
pyruvate dehydrogenase e3-binding protein deficiency
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal; Age of death: adolescent,late childhood;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
variable severity
onset at birth or in early childhood
phenotypic similarities to leigh syndrome ()
patients may or may not have dysmorphic features


HPO:

32
pyruvate dehydrogenase e3-binding protein deficiency:
Inheritance autosomal recessive inheritance
Onset and clinical course variable expressivity congenital onset


Classifications:



External Ids:

KEGG 37 H02003
MeSH 44 D000140
ICD10 via Orphanet 34 E74.4
UMLS via Orphanet 73 C1855553
Orphanet 59 ORPHA255182
MedGen 42 C1855553
UMLS 72 C0268193 C1855553

Summaries for Pyruvate Dehydrogenase E3-Binding Protein Deficiency

KEGG : 37
Defects in the pyruvate dehydrogenase (PDH) complex is a major cause of primary lactic acidosis and neurological dysfunction in infancy. E3 binding protein (E3BP, formerly Protein X) mediates association between the E2 core and the E3 enzyme. Primary defects of the E3BP appear to be a rare cause of pyruvate dehydrogenase deficiency.

MalaCards based summary : Pyruvate Dehydrogenase E3-Binding Protein Deficiency, also known as lacticacidemia due to pdx1 deficiency, is related to pyruvate dehydrogenase e1-alpha deficiency and lactic acidosis, and has symptoms including seizures, ataxia and headache. An important gene associated with Pyruvate Dehydrogenase E3-Binding Protein Deficiency is PDHX (Pyruvate Dehydrogenase Complex Component X), and among its related pathways/superpathways are Metabolism and Viral mRNA Translation. Affiliated tissues include eye, and related phenotypes are hypertelorism and pectus excavatum

UniProtKB/Swiss-Prot : 74 Pyruvate dehydrogenase E3-binding protein deficiency: A metabolic disorder characterized by decreased activity of the pyruvate dehydrogenase complex without observable reduction in the activities of enzymes E1, E2, or E3. Clinical features include hypotonia and psychomotor retardation.

More information from OMIM: 245349 PS312170

Related Diseases for Pyruvate Dehydrogenase E3-Binding Protein Deficiency

Graphical network of the top 20 diseases related to Pyruvate Dehydrogenase E3-Binding Protein Deficiency:



Diseases related to Pyruvate Dehydrogenase E3-Binding Protein Deficiency

Symptoms & Phenotypes for Pyruvate Dehydrogenase E3-Binding Protein Deficiency

Human phenotypes related to Pyruvate Dehydrogenase E3-Binding Protein Deficiency:

32 (show all 26)
# Description HPO Frequency HPO Source Accession
1 hypertelorism 32 HP:0000316
2 pectus excavatum 32 HP:0000767
3 high palate 32 HP:0000218
4 abnormality of eye movement 32 HP:0000496
5 intellectual disability 32 HP:0001249
6 seizures 32 HP:0001250
7 ataxia 32 HP:0001251
8 global developmental delay 32 HP:0001263
9 microcephaly 32 HP:0000252
10 optic atrophy 32 HP:0000648
11 neonatal hypotonia 32 HP:0001319
12 spastic tetraplegia 32 HP:0002510
13 epicanthus 32 HP:0000286
14 poor fine motor coordination 32 HP:0007010
15 dystonia 32 HP:0001332
16 lactic acidosis 32 HP:0003128
17 trigonocephaly 32 HP:0000243
18 metabolic acidosis 32 HP:0001942
19 spastic paraplegia 32 HP:0001258
20 partial agenesis of the corpus callosum 32 HP:0001338
21 increased serum pyruvate 32 HP:0003542
22 hyperalaninemia 32 HP:0003348
23 unsteady gait 32 HP:0002317
24 decreased activity of the pyruvate dehydrogenase complex 32 HP:0002928
25 poor gross motor coordination 32 HP:0007015
26 subependymal cysts 32 HP:0002416

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
hypertelorism
optic atrophy
epicanthal folds
abnormal ocular movements

Neurologic Central Nervous System:
seizures
ataxia
dystonia
spastic paraplegia
unsteady gait
more
Metabolic Features:
lactic acidosis
metabolic acidosis

Chest Ribs Sternum Clavicles And Scapulae:
pectus excavatum (1 patient)

Head And Neck Mouth:
high palate

Head And Neck Head:
microcephaly
trigonocephaly
frontal metopic ridge

Laboratory Abnormalities:
increased serum pyruvate
lacticacidemia
increased serum alanine
decreased activity of the pyruvate dehydrogenase (pdh) complex
decreased levels of component x protein of the pdh complex

Clinical features from OMIM:

245349

UMLS symptoms related to Pyruvate Dehydrogenase E3-Binding Protein Deficiency:


seizures, ataxia, headache, lethargy, cyanosis, dyspnea on exertion

Drugs & Therapeutics for Pyruvate Dehydrogenase E3-Binding Protein Deficiency

Search Clinical Trials , NIH Clinical Center for Pyruvate Dehydrogenase E3-Binding Protein Deficiency

Genetic Tests for Pyruvate Dehydrogenase E3-Binding Protein Deficiency

Genetic tests related to Pyruvate Dehydrogenase E3-Binding Protein Deficiency:

# Genetic test Affiliating Genes
1 Pyruvate Dehydrogenase E3-Binding Protein Deficiency 29 PDHX
2 Lipoamide Dehydrogenase Deficiency 29

Anatomical Context for Pyruvate Dehydrogenase E3-Binding Protein Deficiency

MalaCards organs/tissues related to Pyruvate Dehydrogenase E3-Binding Protein Deficiency:

41
Eye

Publications for Pyruvate Dehydrogenase E3-Binding Protein Deficiency

Articles related to Pyruvate Dehydrogenase E3-Binding Protein Deficiency:

(show all 16)
# Title Authors PMID Year
1
A new case of pyruvate dehydrogenase deficiency due to a novel mutation in the PDX1 gene. 38 8 71
12557299 2003
2
Pyruvate dehydrogenase E3 binding protein deficiency. 38 8 71
11935326 2002
3
Founder p.Arg 446* mutation in the PDHX gene explains over half of cases with congenital lactic acidosis in Roma children. 8 71
25087164 2014
4
Deep sequencing reveals 50 novel genes for recessive cognitive disorders. 8 71
21937992 2011
5
A large genomic deletion in the PDHX gene caused by the retrotranspositional insertion of a full-length LINE-1 element. 8 71
17152059 2007
6
Mutations in PDX1, the human lipoyl-containing component X of the pyruvate dehydrogenase-complex gene on chromosome 11p1, in congenital lactic acidosis. 8 71
9399911 1997
7
Defect in the X-lipoyl-containing component of the pyruvate dehydrogenase complex in a patient with neonatal lactic acidemia. 8 71
8584393 1996
8
Defect in the lipoyl-bearing protein X subunit of the pyruvate dehydrogenase complex in two patients with encephalomyelopathy. 8 71
8229524 1993
9
Lactic acidosis and developmental delay due to deficiency of E3 binding protein (protein X) of the pyruvate dehydrogenase complex. 38 8
15303005 2004
10
Leigh's disease due to a new mutation in the PDHX gene. 71
16566017 2006
11
First prenatal diagnosis of defects in the HsPDX1 gene encoding protein X, an additional lipoyl-containing subunit of the human pyruvate dehydrogenase complex. 8
10590436 1999
12
Detection of a homozygous four base pair deletion in the protein X gene in a case of pyruvate dehydrogenase complex deficiency. 71
9467010 1998
13
Pyruvate dehydrogenase complex deficiency and absence of subunit X. 8
9501264 1998
14
Defects in the E2 lipoyl transacetylase and the X-lipoyl containing component of the pyruvate dehydrogenase complex in patients with lactic acidemia. 8
2112155 1990
15
Mendeliome sequencing enables differential diagnosis and treatment of neonatal lactic acidosis. 38
27317552 2016
16
Primary pyruvate dehydrogenase E3 binding protein deficiency with mild hyperlactataemia and hyperalaninaemia. 38
14518830 2003

Variations for Pyruvate Dehydrogenase E3-Binding Protein Deficiency

ClinVar genetic disease variations for Pyruvate Dehydrogenase E3-Binding Protein Deficiency:

6 (show all 16)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 PDHX NG_013368.1: g.5604_20276del deletion Pathogenic 11:34938280-34952952 11:34916733-34931405
2 PDHX NM_003477.3(PDHX): c.965_1023del (p.Asp322fs) deletion Pathogenic rs1554989996 11:34999671-34999729 11:34978124-34978182
3 PDHX NM_003477.3(PDHX): c.88_91del (p.Lys30fs) deletion Pathogenic rs724159828 11:34938289-34938292 11:34916742-34916745
4 PDHX NM_003477.3(PDHX): c.641+1G> A single nucleotide variant Pathogenic rs724159829 11:34982066-34982066 11:34960519-34960519
5 PDHX NM_003477.3(PDHX): c.1024-1G> A single nucleotide variant Pathogenic rs724159830 11:35006116-35006116 11:34984569-34984569
6 PDHX NM_003477.3(PDHX): c.620del (p.Pro207fs) deletion Pathogenic rs724159979 11:34982044-34982044 11:34960497-34960497
7 PDHX AJ298105.1: g.61273_107768delins6086 deletion Pathogenic
8 PDHX NM_003477.3(PDHX): c.742C> T (p.Gln248Ter) single nucleotide variant Pathogenic rs113309941 11:34988287-34988287 11:34966740-34966740
9 PDHX NM_003477.3(PDHX): c.1183-3088_1247+760del deletion Pathogenic 11:35010774-35014686 11:34989227-34993139
10 PDHX NM_003477.3(PDHX): c.1336C> T (p.Arg446Ter) single nucleotide variant Pathogenic rs1135402725 11:35016549-35016549 11:34995002-34995002
11 PDHX NM_003477.3(PDHX): c.134G> A (p.Trp45Ter) single nucleotide variant Likely pathogenic rs1064796807 11:34938336-34938336 11:34916789-34916789
12 PDHX NM_003477.3(PDHX): c.589C> A (p.Leu197Met) single nucleotide variant Uncertain significance rs139052284 11:34982013-34982013 11:34960466-34960466
13 PDHX NM_003477.3(PDHX): c.1129A> G (p.Ile377Val) single nucleotide variant Uncertain significance rs75430333 11:35006222-35006222 11:34984675-34984675
14 PDHX NM_003477.3(PDHX): c.403G> T (p.Gly135Ter) single nucleotide variant Uncertain significance 11:34978991-34978991 11:34957444-34957444
15 PDHX NM_003477.3(PDHX): c.44G> A (p.Arg15His) single nucleotide variant Uncertain significance rs387906998 11:34938246-34938246 11:34916699-34916699
16 PDHX NM_003477.3(PDHX): c.479G> A (p.Arg160His) single nucleotide variant not provided rs747386411 11:34979067-34979067 11:34957520-34957520

Expression for Pyruvate Dehydrogenase E3-Binding Protein Deficiency

Search GEO for disease gene expression data for Pyruvate Dehydrogenase E3-Binding Protein Deficiency.

Pathways for Pyruvate Dehydrogenase E3-Binding Protein Deficiency

Pathways related to Pyruvate Dehydrogenase E3-Binding Protein Deficiency according to GeneCards Suite gene sharing:

(show all 11)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.43 PDHX PDHA1 DLD APIP
2
Show member pathways
13.11 PDHX PDHA1 DLD APIP
3
Show member pathways
12.93 PDHX PDHA1 DLD
4
Show member pathways
12.08 PDHX PDHA1 DLD
5
Show member pathways
11.78 PDHA1 DLD
6
Show member pathways
11.55 PDHX PDHA1 DLD
7
Show member pathways
11.45 PDHA1 DLD
8 11.29 PDHX PDHA1 DLD
9
Show member pathways
10.99 PDHA1 DLD
10
Show member pathways
10.95 PDHX PDHA1 DLD
11
Show member pathways
10.41 PDHX PDHA1 DLD

GO Terms for Pyruvate Dehydrogenase E3-Binding Protein Deficiency

Cellular components related to Pyruvate Dehydrogenase E3-Binding Protein Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 9.33 PDHX PDHA1 DLD
2 mitochondrial matrix GO:0005759 9.13 PDHX PDHA1 DLD
3 pyruvate dehydrogenase complex GO:0045254 8.8 PDHX PDHA1 DLD

Biological processes related to Pyruvate Dehydrogenase E3-Binding Protein Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 acetyl-CoA biosynthetic process from pyruvate GO:0006086 8.96 PDHA1 DLD
2 mitochondrial acetyl-CoA biosynthetic process from pyruvate GO:0061732 8.8 PDHX PDHA1 DLD

Molecular functions related to Pyruvate Dehydrogenase E3-Binding Protein Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 pyruvate dehydrogenase (NAD+) activity GO:0034604 8.8 PDHX PDHA1 DLD

Sources for Pyruvate Dehydrogenase E3-Binding Protein Deficiency

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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