PDHDD
MCID: PYR025
MIFTS: 31

Pyruvate Dehydrogenase E2 Deficiency (PDHDD)

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

Aliases & Classifications for Pyruvate Dehydrogenase E2 Deficiency

MalaCards integrated aliases for Pyruvate Dehydrogenase E2 Deficiency:

Name: Pyruvate Dehydrogenase E2 Deficiency 57 58 72 36 29 13 6 39 70
Lactic Acidemia Due to Defect of E2 Lipoyl Transacetylase of the Pyruvate Dehydrogenase Complex 57 72
Dihydrolipoyllysine-Residue Acetyltransferase Component of Pyruvate Dehydrogenase Complex Deficiency 58
Dihydrolipoamide Acetyltransferase Component of Pyruvate Dehydrogenase Complex Deficiency 58
Pyruvate Dehydrogenase Complex Component E2 Deficiency 58
Pdhe2 Deficiency 72
Pdhdd 57

Characteristics:

Orphanet epidemiological data:

58
pyruvate dehydrogenase e2 deficiency
Inheritance: Autosomal recessive; Age of onset: Childhood; Age of death: adolescent,late childhood;

OMIM®:

57 (Updated 05-Apr-2021)
Miscellaneous:
very rare
onset in infancy

Inheritance:
autosomal recessive


HPO:

31
pyruvate dehydrogenase e2 deficiency:
Inheritance autosomal recessive inheritance
Onset and clinical course infantile onset
very rare


Classifications:

Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism


Summaries for Pyruvate Dehydrogenase E2 Deficiency

KEGG : 36 Defects in the pyruvate dehydrogenase (PDH) complex is a major cause of primary lactic acidosis and neurological dysfunction in infancy. Recently, mutations in DLAT, the gene encoding dihydrolipoamide acetyltransferase, the E2 core component of the complex, have been described. Patients are less severely affected than typical patients with E1 mutations. Episodic dystonia was the major neurological manifestation.

MalaCards based summary : Pyruvate Dehydrogenase E2 Deficiency, also known as lactic acidemia due to defect of e2 lipoyl transacetylase of the pyruvate dehydrogenase complex, is related to neurodegeneration with brain iron accumulation 1 and pyruvate dehydrogenase e1-beta deficiency, and has symptoms including ataxia and dystonia, paroxysmal. An important gene associated with Pyruvate Dehydrogenase E2 Deficiency is DLAT (Dihydrolipoamide S-Acetyltransferase), and among its related pathways/superpathways are Glycolysis / Gluconeogenesis and Pyruvate metabolism. Affiliated tissues include globus pallidus and eye, and related phenotypes are abnormal enzyme/coenzyme activity and difficulty walking

UniProtKB/Swiss-Prot : 72 Pyruvate dehydrogenase E2 deficiency: Pyruvate dehydrogenase (PDH) deficiency is a major cause of primary lactic acidosis and neurological dysfunction in infancy and early childhood. In this form of PDH deficiency episodic dystonia is the major neurological manifestation, with other more common features of pyruvate dehydrogenase deficiency, such as hypotonia and ataxia, being less prominent.

More information from OMIM: 245348 PS312170

Related Diseases for Pyruvate Dehydrogenase E2 Deficiency

Diseases related to Pyruvate Dehydrogenase E2 Deficiency via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 neurodegeneration with brain iron accumulation 1 10.1
2 pyruvate dehydrogenase e1-beta deficiency 10.1
3 dystonia 10.1
4 learning disability 10.1
5 pyruvate dehydrogenase e1-alpha deficiency 9.5 PIH1D2 DLAT

Graphical network of the top 20 diseases related to Pyruvate Dehydrogenase E2 Deficiency:



Diseases related to Pyruvate Dehydrogenase E2 Deficiency

Symptoms & Phenotypes for Pyruvate Dehydrogenase E2 Deficiency

Human phenotypes related to Pyruvate Dehydrogenase E2 Deficiency:

58 31 (show all 48)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 abnormal enzyme/coenzyme activity 58 31 hallmark (90%) Very frequent (99-80%) HP:0012379
2 difficulty walking 58 31 hallmark (90%) Very frequent (99-80%) HP:0002355
3 low levels of vitamin b1 58 31 hallmark (90%) Very frequent (99-80%) HP:0100503
4 abnormal csf pyruvate family amino acid concentration 58 31 hallmark (90%) Very frequent (99-80%) HP:0500231
5 dysarthria 58 31 frequent (33%) Frequent (79-30%) HP:0001260
6 global developmental delay 58 31 frequent (33%) Frequent (79-30%) HP:0001263
7 hypertonia 58 31 frequent (33%) Frequent (79-30%) HP:0001276
8 intellectual disability, severe 58 31 frequent (33%) Frequent (79-30%) HP:0010864
9 broad-based gait 58 31 frequent (33%) Frequent (79-30%) HP:0002136
10 babinski sign 58 31 frequent (33%) Frequent (79-30%) HP:0003487
11 retinal degeneration 58 31 frequent (33%) Frequent (79-30%) HP:0000546
12 positional foot deformity 58 31 frequent (33%) Frequent (79-30%) HP:0005656
13 lower limb hyperreflexia 58 31 frequent (33%) Frequent (79-30%) HP:0002395
14 neurodegeneration 58 31 frequent (33%) Frequent (79-30%) HP:0002180
15 eye of the tiger anomaly of globus pallidus 58 31 frequent (33%) Frequent (79-30%) HP:0002454
16 upgaze palsy 58 31 frequent (33%) Frequent (79-30%) HP:0025331
17 frog-leg posture 58 31 frequent (33%) Frequent (79-30%) HP:0031139
18 paroxysmal dystonia 58 31 frequent (33%) Frequent (79-30%) HP:0002268
19 iron accumulation in globus pallidus 58 31 frequent (33%) Frequent (79-30%) HP:0012677
20 delayed ability to walk 58 31 frequent (33%) Frequent (79-30%) HP:0031936
21 delayed ability to stand 58 31 frequent (33%) Frequent (79-30%) HP:0025335
22 arm dystonia 58 31 frequent (33%) Frequent (79-30%) HP:0031960
23 microcephaly 58 31 occasional (7.5%) Occasional (29-5%) HP:0000252
24 strabismus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000486
25 anxiety 58 31 occasional (7.5%) Occasional (29-5%) HP:0000739
26 dementia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000726
27 speech apraxia 58 31 occasional (7.5%) Occasional (29-5%) HP:0011098
28 peripheral visual field loss 58 31 occasional (7.5%) Occasional (29-5%) HP:0007994
29 hyperreflexia 31 HP:0001347
30 abnormality of eye movement 58 Frequent (79-30%)
31 ptosis 31 HP:0000508
32 nystagmus 31 HP:0000639
33 ataxia 31 HP:0001251
34 gait disturbance 58 Frequent (79-30%)
35 behavioral abnormality 58 Frequent (79-30%)
36 neonatal hypotonia 31 HP:0001319
37 intellectual disability, mild 31 HP:0001256
38 abnormality of the nervous system 58 Frequent (79-30%)
39 lactic acidosis 31 HP:0003128
40 choreoathetosis 31 HP:0001266
41 psychomotor retardation 31 HP:0025356
42 delayed gross motor development 31 HP:0002194
43 oculomotor apraxia 31 HP:0000657
44 functional motor deficit 58 Occasional (29-5%)
45 poor speech 31 HP:0002465
46 drooling 31 HP:0002307
47 jerky head movements 31 HP:0006961
48 decreased activity of the pyruvate dehydrogenase complex 31 HP:0002928

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
hyperreflexia
ataxia
psychomotor retardation
poor speech
drooling
more
Head And Neck Head:
microcephaly

Laboratory Abnormalities:
serum and csf lactate may be increased
decreased activity of the pyruvate dehydrogenase complex (pdh)
decreased activity of the e2 subunit (lipoyl transacetylase, ) of the pdh
decreased levels of the e2 subunit protein

Head And Neck Eyes:
ptosis
nystagmus
oculomotor apraxia
saccade initiation failure

Metabolic Features:
lactic acidosis, may be mild

Clinical features from OMIM®:

245348 (Updated 05-Apr-2021)

UMLS symptoms related to Pyruvate Dehydrogenase E2 Deficiency:


ataxia; dystonia, paroxysmal

Drugs & Therapeutics for Pyruvate Dehydrogenase E2 Deficiency

Search Clinical Trials , NIH Clinical Center for Pyruvate Dehydrogenase E2 Deficiency

Genetic Tests for Pyruvate Dehydrogenase E2 Deficiency

Genetic tests related to Pyruvate Dehydrogenase E2 Deficiency:

# Genetic test Affiliating Genes
1 Pyruvate Dehydrogenase E2 Deficiency 29 DLAT

Anatomical Context for Pyruvate Dehydrogenase E2 Deficiency

MalaCards organs/tissues related to Pyruvate Dehydrogenase E2 Deficiency:

40
Globus Pallidus, Eye

Publications for Pyruvate Dehydrogenase E2 Deficiency

Articles related to Pyruvate Dehydrogenase E2 Deficiency:

# Title Authors PMID Year
1
Pyruvate dehydrogenase complex-E2 deficiency causes paroxysmal exercise-induced dyskinesia. 57 6
29093066 2017
2
Clinical and genetic spectrum of pyruvate dehydrogenase deficiency: dihydrolipoamide acetyltransferase (E2) deficiency. 6 57
16049940 2005
3
Defects in the E2 lipoyl transacetylase and the X-lipoyl containing component of the pyruvate dehydrogenase complex in patients with lactic acidemia. 57
2112155 1990
4
Pyruvate dehydrogenase E2 deficiency: a potentially treatable cause of episodic dystonia. 61
20022530 2010

Variations for Pyruvate Dehydrogenase E2 Deficiency

ClinVar genetic disease variations for Pyruvate Dehydrogenase E2 Deficiency:

6 (show all 38)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 DLAT DLAT, 3-BP DEL, 361GAA Deletion Pathogenic 2109 GRCh37:
GRCh38:
2 PIH1D2 , DLAT NM_001931.5(DLAT):c.1728C>A (p.Phe576Leu) SNV Pathogenic 2110 rs119103240 GRCh37: 11:111931812-111931812
GRCh38: 11:112061088-112061088
3 DLAT NM_001931.5(DLAT):c.470T>G (p.Val157Gly) SNV Pathogenic 208790 rs797044957 GRCh37: 11:111899327-111899327
GRCh38: 11:112028603-112028603
4 DLAT NC_000011.9:g.(?_111896177)_(111922093_?)del Deletion Pathogenic 832069 GRCh37: 11:111896177-111922093
GRCh38:
5 DLAT NM_001931.5(DLAT):c.976-1G>A SNV Pathogenic 432212 rs367875541 GRCh37: 11:111909967-111909967
GRCh38: 11:112039243-112039243
6 PIH1D2 , DLAT NM_001931.5(DLAT):c.1934TGT[2] (p.Leu647del) Microsatellite Pathogenic 1033461 GRCh37: 11:111933249-111933251
GRCh38: 11:112062525-112062527
7 DLAT NM_001931.5(DLAT):c.848_849del (p.Asp283fs) Deletion Likely pathogenic 434944 rs782704553 GRCh37: 11:111908057-111908058
GRCh38: 11:112037333-112037334
8 DLAT NM_001931.5(DLAT):c.396dup (p.Ala133fs) Duplication Conflicting interpretations of pathogenicity 631650 rs782173047 GRCh37: 11:111899250-111899251
GRCh38: 11:112028526-112028527
9 DLAT NM_001931.5(DLAT):c.202A>T (p.Thr68Ser) SNV Uncertain significance 1029549 GRCh37: 11:111896398-111896398
GRCh38: 11:112025674-112025674
10 DLAT NM_001931.5(DLAT):c.956C>T (p.Pro319Leu) SNV Uncertain significance 1029550 GRCh37: 11:111908165-111908165
GRCh38: 11:112037441-112037441
11 DLAT NM_001931.5(DLAT):c.1289G>A (p.Arg430Gln) SNV Uncertain significance 955752 GRCh37: 11:111915953-111915953
GRCh38: 11:112045229-112045229
12 DLAT NM_001931.5(DLAT):c.343G>A (p.Glu115Lys) SNV Uncertain significance 1041771 GRCh37: 11:111896985-111896985
GRCh38: 11:112026261-112026261
13 DLAT NM_001931.5(DLAT):c.355A>G (p.Ile119Val) SNV Uncertain significance 534585 rs1555179245 GRCh37: 11:111896997-111896997
GRCh38: 11:112026273-112026273
14 DLAT NM_001931.5(DLAT):c.1202C>T (p.Pro401Leu) SNV Uncertain significance 547881 rs781794850 GRCh37: 11:111915866-111915866
GRCh38: 11:112045142-112045142
15 DLAT NM_001931.5(DLAT):c.1310T>G (p.Met437Arg) SNV Uncertain significance 1000966 GRCh37: 11:111916606-111916606
GRCh38: 11:112045882-112045882
16 DLAT NM_001931.5(DLAT):c.1406A>G (p.Glu469Gly) SNV Uncertain significance 1002009 GRCh37: 11:111921965-111921965
GRCh38: 11:112051241-112051241
17 DLAT NM_001931.5(DLAT):c.1384A>C (p.Lys462Gln) SNV Uncertain significance 961474 GRCh37: 11:111916680-111916680
GRCh38: 11:112045956-112045956
18 DLAT NM_001931.5(DLAT):c.382G>A (p.Val128Ile) SNV Uncertain significance 596741 rs144677434 GRCh37: 11:111899239-111899239
GRCh38: 11:112028515-112028515
19 PIH1D2 , DLAT NM_001931.5(DLAT):c.1712T>C (p.Phe571Ser) SNV Uncertain significance 838535 GRCh37: 11:111931796-111931796
GRCh38: 11:112061072-112061072
20 DLAT NM_001931.5(DLAT):c.32A>C (p.Asn11Thr) SNV Uncertain significance 841563 GRCh37: 11:111896228-111896228
GRCh38: 11:112025504-112025504
21 DLAT NM_001931.5(DLAT):c.983C>T (p.Ala328Val) SNV Uncertain significance 856329 GRCh37: 11:111909975-111909975
GRCh38: 11:112039251-112039251
22 DLAT NM_001931.5(DLAT):c.1399A>C (p.Ile467Leu) SNV Uncertain significance 930797 GRCh37: 11:111921958-111921958
GRCh38: 11:112051234-112051234
23 DLAT NM_001931.5(DLAT):c.572C>T (p.Ala191Val) SNV Uncertain significance 214292 rs200500508 GRCh37: 11:111899581-111899581
GRCh38: 11:112028857-112028857
24 DLAT NM_001931.5(DLAT):c.675C>T (p.Ala225=) SNV Likely benign 386351 rs782220140 GRCh37: 11:111904142-111904142
GRCh38: 11:112033418-112033418
25 DLAT NM_001931.5(DLAT):c.946C>T (p.Pro316Ser) SNV Likely benign 302456 rs149088081 GRCh37: 11:111908155-111908155
GRCh38: 11:112037431-112037431
26 DLAT NM_001931.5(DLAT):c.1142A>G (p.Asp381Gly) SNV Likely benign 302459 rs144235197 GRCh37: 11:111914202-111914202
GRCh38: 11:112043478-112043478
27 DLAT NM_001931.5(DLAT):c.1476C>T (p.Pro492=) SNV Likely benign 744090 rs370501604 GRCh37: 11:111922035-111922035
GRCh38: 11:112051311-112051311
28 DLAT NM_001931.5(DLAT):c.969A>C (p.Pro323=) SNV Likely benign 746386 rs587627931 GRCh37: 11:111908178-111908178
GRCh38: 11:112037454-112037454
29 DLAT NM_001931.5(DLAT):c.628G>A (p.Ala210Thr) SNV Likely benign 214294 rs140678772 GRCh37: 11:111899637-111899637
GRCh38: 11:112028913-112028913
30 DLAT NM_001931.5(DLAT):c.144G>A (p.Val48=) SNV Likely benign 534586 rs367745211 GRCh37: 11:111896340-111896340
GRCh38: 11:112025616-112025616
31 DLAT NM_001931.5(DLAT):c.1035A>G (p.Pro345=) SNV Likely benign 374698 rs140302942 GRCh37: 11:111910027-111910027
GRCh38: 11:112039303-112039303
32 DLAT NM_001931.4(DLAT):c.381+22delT Deletion Benign/Likely benign 522242 rs5794771 GRCh37: 11:111897029-111897029
GRCh38: 11:112026305-112026305
33 DLAT NM_001931.5(DLAT):c.570A>G (p.Gln190=) SNV Benign/Likely benign 137089 rs143107853 GRCh37: 11:111899579-111899579
GRCh38: 11:112028855-112028855
34 DLAT NM_001931.5(DLAT):c.46G>A (p.Ala16Thr) SNV Benign 137085 rs150145390 GRCh37: 11:111896242-111896242
GRCh38: 11:112025518-112025518
35 DLAT NM_001931.5(DLAT):c.928G>A (p.Glu310Lys) SNV Benign 137087 rs116125936 GRCh37: 11:111908137-111908137
GRCh38: 11:112037413-112037413
36 DLAT NM_001931.5(DLAT):c.55G>C (p.Glu19Gln) SNV Benign 137086 rs61757217 GRCh37: 11:111896251-111896251
GRCh38: 11:112025527-112025527
37 DLAT NM_001931.5(DLAT):c.626A>G (p.Gln209Arg) SNV Benign 137090 rs11553595 GRCh37: 11:111899635-111899635
GRCh38: 11:112028911-112028911
38 DLAT NM_001931.5(DLAT):c.693C>T (p.Thr231=) SNV Benign 137091 rs34680691 GRCh37: 11:111904160-111904160
GRCh38: 11:112033436-112033436

Expression for Pyruvate Dehydrogenase E2 Deficiency

Search GEO for disease gene expression data for Pyruvate Dehydrogenase E2 Deficiency.

Pathways for Pyruvate Dehydrogenase E2 Deficiency

Pathways related to Pyruvate Dehydrogenase E2 Deficiency according to KEGG:

36
# Name Kegg Source Accession
1 Glycolysis / Gluconeogenesis hsa00010
2 Pyruvate metabolism hsa00620

GO Terms for Pyruvate Dehydrogenase E2 Deficiency

Sources for Pyruvate Dehydrogenase E2 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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