PDHXD
MCID: PYR031
MIFTS: 42

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 56 58 73 36 29 6 39 71
Lacticacidemia Due to Pdx1 Deficiency 56 73 13
Lactic Acidemia Due to Defect in Lipoyl-Containing Component X of the Pyruvate Dehydrogenase Complex 56 73
Lipoamide Dehydrogenase Deficiency 58 29
Pdhxd 56 73
Branched Chain Alpha-Ketoacid Dehydrogenase Complex Deficiency 58
Pyruvate Dehydrogenase Complex Component E3 Deficiency 58
Pyruvate Dehydrogenase Protein X Component Deficiency 58
Glycine Cleavage System L Protein Deficiency 58
Nadh Cytochrome B5 Reductase Deficiency 71
Dihydrolipoyl Dehydrogenase Deficiency 58
2-Oxoglutarate Complex Deficiency 58
Diaphorase Deficiency 58

Characteristics:

Orphanet epidemiological data:

58
pyruvate dehydrogenase e3-binding protein deficiency
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal; Age of death: adolescent,late childhood;

OMIM:

56
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:

31
pyruvate dehydrogenase e3-binding protein deficiency:
Inheritance autosomal recessive inheritance
Onset and clinical course variable expressivity congenital onset


Classifications:

Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism
Developmental anomalies during embryogenesis


Summaries for Pyruvate Dehydrogenase E3-Binding Protein Deficiency

KEGG : 36 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 intellectual disability and global developmental delay

UniProtKB/Swiss-Prot : 73 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:

31 (show all 26)
# Description HPO Frequency HPO Source Accession
1 intellectual disability 31 HP:0001249
2 global developmental delay 31 HP:0001263
3 hypertelorism 31 HP:0000316
4 microcephaly 31 HP:0000252
5 optic atrophy 31 HP:0000648
6 neonatal hypotonia 31 HP:0001319
7 spastic tetraplegia 31 HP:0002510
8 ataxia 31 HP:0001251
9 high palate 31 HP:0000218
10 epicanthus 31 HP:0000286
11 pectus excavatum 31 HP:0000767
12 abnormality of eye movement 31 HP:0000496
13 dystonia 31 HP:0001332
14 spastic paraplegia 31 HP:0001258
15 partial agenesis of the corpus callosum 31 HP:0001338
16 trigonocephaly 31 HP:0000243
17 lactic acidosis 31 HP:0003128
18 increased serum pyruvate 31 HP:0003542
19 metabolic acidosis 31 HP:0001942
20 unsteady gait 31 HP:0002317
21 hyperalaninemia 31 HP:0003348
22 poor fine motor coordination 31 HP:0007010
23 poor gross motor coordination 31 HP:0007015
24 decreased activity of the pyruvate dehydrogenase complex 31 HP:0002928
25 subependymal cysts 31 HP:0002416
26 seizure 31 HP:0001250

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Eyes:
hypertelorism
optic atrophy
epicanthal folds
abnormal ocular movements

Head And Neck Head:
microcephaly
trigonocephaly
frontal metopic ridge

Metabolic Features:
lactic acidosis
metabolic acidosis

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

Neurologic Central Nervous System:
seizures
ataxia
dystonia
spastic paraplegia
unsteady gait
more
Head And Neck Mouth:
high palate

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

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

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-122 9.23 PDHA1
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-170 9.23 DLD
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-24 9.23 DLD
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-35 9.23 DLD
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-42 9.23 DLD
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-51 9.23 DLD
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-60 9.23 PDHA1
8 Decreased shRNA abundance (Z-score < -2) GR00366-A-77 9.23 DLD

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:

40
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. 56 6 61
12557299 2003
2
Pyruvate dehydrogenase E3 binding protein deficiency. 56 6 61
11935326 2002
3
Founder p.Arg 446* mutation in the PDHX gene explains over half of cases with congenital lactic acidosis in Roma children. 6 56
25087164 2014
4
Deep sequencing reveals 50 novel genes for recessive cognitive disorders. 6 56
21937992 2011
5
A large genomic deletion in the PDHX gene caused by the retrotranspositional insertion of a full-length LINE-1 element. 6 56
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. 6 56
9399911 1997
7
Defect in the X-lipoyl-containing component of the pyruvate dehydrogenase complex in a patient with neonatal lactic acidemia. 56 6
8584393 1996
8
Defect in the lipoyl-bearing protein X subunit of the pyruvate dehydrogenase complex in two patients with encephalomyelopathy. 6 56
8229524 1993
9
Lactic acidosis and developmental delay due to deficiency of E3 binding protein (protein X) of the pyruvate dehydrogenase complex. 56 61
15303005 2004
10
Leigh's disease due to a new mutation in the PDHX gene. 6
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. 56
10590436 1999
12
Detection of a homozygous four base pair deletion in the protein X gene in a case of pyruvate dehydrogenase complex deficiency. 6
9467010 1998
13
Pyruvate dehydrogenase complex deficiency and absence of subunit X. 56
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. 56
2112155 1990
15
Mendeliome sequencing enables differential diagnosis and treatment of neonatal lactic acidosis. 61
27317552 2016
16
Primary pyruvate dehydrogenase E3 binding protein deficiency with mild hyperlactataemia and hyperalaninaemia. 61
14518830 2003

Variations for Pyruvate Dehydrogenase E3-Binding Protein Deficiency

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

6 (show top 50) (show all 97) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 PDHX NG_013368.1:g.5604_20276deldeletion Pathogenic 2111 11:34938280-34952952 11:34916733-34931405
2 PDHX NM_003477.3(PDHX):c.965_1023del (p.Asp322fs)deletion Pathogenic 2112 rs1554989996 11:34999671-34999729 11:34978124-34978182
3 PDHX NM_003477.3(PDHX):c.88_91del (p.Lys30fs)deletion Pathogenic 2113 rs724159828 11:34938289-34938292 11:34916742-34916745
4 PDHX NM_003477.3(PDHX):c.641+1G>ASNV Pathogenic 2114 rs724159829 11:34982066-34982066 11:34960519-34960519
5 PDHX NM_003477.3(PDHX):c.1024-1G>ASNV Pathogenic 2115 rs724159830 11:35006116-35006116 11:34984569-34984569
6 PDHX NM_003477.3(PDHX):c.620del (p.Pro207fs)deletion Pathogenic 2116 rs724159979 11:34982042-34982042 11:34960495-34960495
7 PDHX AJ298105.1:g.61273_107768delins6086deletion Pathogenic 2117
8 PDHX NM_003477.3(PDHX):c.742C>T (p.Gln248Ter)SNV Pathogenic 2118 rs113309941 11:34988287-34988287 11:34966740-34966740
9 PDHX NM_003477.3(PDHX):c.1183-3088_1247+760deldeletion Pathogenic 2119 11:35010771-35014683 11:34989224-34993136
10 PDHX NM_003477.3(PDHX):c.1336C>T (p.Arg446Ter)SNV Pathogenic 162202 rs1135402725 11:35016549-35016549 11:34995002-34995002
11 PDHX NM_003477.3(PDHX):c.134G>A (p.Trp45Ter)SNV Likely pathogenic 424121 rs1064796807 11:34938336-34938336 11:34916789-34916789
12 PDHX NM_003477.3(PDHX):c.242-4G>ASNV Conflicting interpretations of pathogenicity 737899 11:34969049-34969049 11:34947502-34947502
13 PDHX NM_003477.3(PDHX):c.976G>C (p.Val326Leu)SNV Conflicting interpretations of pathogenicity 138664 rs35560997 11:34999682-34999682 11:34978135-34978135
14 PDHX NM_003477.3(PDHX):c.161-6T>CSNV Conflicting interpretations of pathogenicity 304462 rs200438675 11:34952945-34952945 11:34931398-34931398
15 PDHX NM_003477.3(PDHX):c.579A>G (p.Glu193=)SNV Conflicting interpretations of pathogenicity 214955 rs61752926 11:34982003-34982003 11:34960456-34960456
16 PDHX NM_003477.3(PDHX):c.589C>A (p.Leu197Met)SNV Conflicting interpretations of pathogenicity 214960 rs139052284 11:34982013-34982013 11:34960466-34960466
17 PDHX NM_003477.3(PDHX):c.640G>C (p.Glu214Gln)SNV Conflicting interpretations of pathogenicity 214962 rs146445744 11:34982064-34982064 11:34960517-34960517
18 PDHX NM_003477.3(PDHX):c.674C>T (p.Thr225Met)SNV Conflicting interpretations of pathogenicity 214956 rs148645836 11:34988219-34988219 11:34966672-34966672
19 PDHX NM_003477.3(PDHX):c.749C>T (p.Thr250Ile)SNV Conflicting interpretations of pathogenicity 214963 rs146876119 11:34988294-34988294 11:34966747-34966747
20 PDHX NM_003477.3(PDHX):c.542+10T>CSNV Conflicting interpretations of pathogenicity 304467 rs368960575 11:34979140-34979140 11:34957593-34957593
21 PDHX NM_003477.3(PDHX):c.47A>C (p.Tyr16Ser)SNV Conflicting interpretations of pathogenicity 304461 rs118136428 11:34938249-34938249 11:34916702-34916702
22 PDHX NM_003477.3(PDHX):c.702T>C (p.Thr234=)SNV Uncertain significance 304471 rs772231144 11:34988247-34988247 11:34966700-34966700
23 PDHX NM_003477.3(PDHX):c.403G>T (p.Gly135Ter)SNV Uncertain significance 632159 rs769476738 11:34978991-34978991 11:34957444-34957444
24 PDHX NM_001135024.1(PDHX):c.115+15G>ASNV Uncertain significance 304455 rs886048246 11:34938048-34938048 11:34916501-34916501
25 PDHX NM_003477.3(PDHX):c.*259G>TSNV Uncertain significance 304479 rs771515806 11:35016978-35016978 11:34995431-34995431
26 PDHX NM_003477.3(PDHX):c.*331G>CSNV Uncertain significance 304480 rs555691861 11:35017050-35017050 11:34995503-34995503
27 PDHX NM_003477.3(PDHX):c.*743G>ASNV Uncertain significance 304484 rs577162977 11:35017462-35017462 11:34995915-34995915
28 PDHX NM_003477.3(PDHX):c.-7C>TSNV Uncertain significance 304460 rs751680964 11:34938196-34938196 11:34916649-34916649
29 PDHX NM_003477.3(PDHX):c.577G>C (p.Glu193Gln)SNV Uncertain significance 304468 rs149337104 11:34982001-34982001 11:34960454-34960454
30 PDHX NM_003477.3(PDHX):c.585C>G (p.His195Gln)SNV Uncertain significance 304469 rs886048247 11:34982009-34982009 11:34960462-34960462
31 PDHX NM_003477.3(PDHX):c.841A>G (p.Ser281Gly)SNV Uncertain significance 304472 rs886048248 11:34991710-34991710 11:34970163-34970163
32 PDHX NM_003477.3(PDHX):c.1129A>G (p.Ile377Val)SNV Uncertain significance 214958 rs75430333 11:35006222-35006222 11:34984675-34984675
33 PDHX NM_003477.3(PDHX):c.317A>G (p.Asp106Gly)SNV Uncertain significance 282337 rs146456454 11:34969128-34969128 11:34947581-34947581
34 PDHX NM_003477.3(PDHX):c.511G>A (p.Val171Ile)SNV Uncertain significance 304465 rs142256229 11:34979099-34979099 11:34957552-34957552
35 PDHX NM_015957.4(APIP):c.-1C>TSNV Uncertain significance 304446 rs774565620 11:34937832-34937832 11:34916285-34916285
36 PDHX NM_003477.3(PDHX):c.*650G>ASNV Uncertain significance 304483 rs886048249 11:35017369-35017369 11:34995822-34995822
37 PDHX NM_003477.3(PDHX):c.*763G>ASNV Uncertain significance 304485 rs886048250 11:35017482-35017482 11:34995935-34995935
38 PDHX NM_015957.4(APIP):c.-14C>TSNV Uncertain significance 304447 rs886048245 11:34937845-34937845 11:34916298-34916298
39 PDHX NM_015957.4(APIP):c.-18G>ASNV Uncertain significance 304448 rs761199870 11:34937849-34937849 11:34916302-34916302
40 PDHX NM_015957.4(APIP):c.57+57C>GSNV Uncertain significance 877364 11:34937718-34937718 11:34916171-34916171
41 PDHX NM_001135024.1(PDHX):c.115+8C>ASNV Uncertain significance 878391 11:34938041-34938041 11:34916494-34916494
42 PDHX NM_003477.3(PDHX):c.-27C>TSNV Uncertain significance 878981 11:34938176-34938176 11:34916629-34916629
43 PDHX NM_003477.3(PDHX):c.35G>A (p.Arg12Gln)SNV Uncertain significance 878982 11:34938237-34938237 11:34916690-34916690
44 PDHX NM_003477.3(PDHX):c.402A>G (p.Glu134=)SNV Uncertain significance 877419 11:34978990-34978990 11:34957443-34957443
45 PDHX NM_003477.3(PDHX):c.940A>G (p.Lys314Glu)SNV Uncertain significance 879035 11:34991809-34991809 11:34970262-34970262
46 PDHX NM_003477.3(PDHX):c.1164A>G (p.Glu388=)SNV Uncertain significance 880249 11:35006257-35006257 11:34984710-34984710
47 PDHX NM_003477.3(PDHX):c.1450A>G (p.Thr484Ala)SNV Uncertain significance 880250 11:35016663-35016663 11:34995116-34995116
48 PDHX NM_003477.3(PDHX):c.*662A>TSNV Uncertain significance 878502 11:35017381-35017381 11:34995834-34995834
49 PDHX NM_003477.3(PDHX):c.*742C>TSNV Uncertain significance 878503 11:35017461-35017461 11:34995914-34995914
50 PDHX NM_003477.3(PDHX):c.*783G>TSNV Uncertain significance 878504 11:35017502-35017502 11:34995955-34995955

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
13.45 PDHX PDHA1 DLD APIP
2
Show member pathways
13.11 PDHX PDHA1 DLD APIP
3
Show member pathways
12.69 PDHX PDHA1 DLD
4
Show member pathways
12.08 PDHX PDHA1 DLD
5
Show member pathways
11.8 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
10.34 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 tricarboxylic acid cycle GO:0006099 9.26 PDHA1 DLD
2 acetyl-CoA biosynthetic process from pyruvate GO:0006086 9.16 PDHA1 DLD
3 pyruvate metabolic process GO:0006090 9.13 PDHX PDHA1 DLD
4 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 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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