MSeqDR Mitochondrial Disease Portal


 
*:HP: HPO terms, UMDF: 1= Disease, ND: NAMDC terms.
  Most Studied  CPEO, Complex I Deficiency, COXPD1, Leigh, LHON, MELAS, MERRF, Myopathy, SANDO
Term ID:9545
Name:Pyruvate Dehydrogenase Complex Deficiency Disease
Definition:An inherited metabolic disorder caused by deficient enzyme activity in the PYRUVATE DEHYDROGENASE COMPLEX, resulting in deficiency of acetyl CoA and reduced synthesis of acetylcholine. Two clinical forms are recognized: neonatal and juvenile. The neonatal form is a relatively common cause of lactic acidosis in the first weeks of life and may also feature an erythematous rash. The juvenile form presents with lactic acidosis, alopecia, intermittent ATAXIA; SEIZURES; and an erythematous rash. (From J Inherit Metab Dis 1996;19(4):452-62) Autosomal recessive and X-linked forms are caused by mutations in the genes for the three different enzyme components of this multisubunit pyruvate dehydrogenase complex. One of the mutations at Xp22.2-p22.1 in the gene for the E1 alpha component of the complex leads to LEIGH DISEASE.
Alternative IDs:OMIM:312170
ParentIDs:MESH:D015323|MESH:D020739|MESH:D028361|MESH:D038901
TreeNumbers:C10.228.140.163.100.750 |C10.597.606.643.455.875 |C16.320.322.500.875 |C16.320.400.525.875 |C16.320.565.189.750 |C16.320.565.202.810.766 |C18.452.132.100.750 |C18.452.648.189.750 |C18.452.648.202.810.766 |C18.452.660.710
Synonyms:Ataxia, Intermittent, with Abnormal Pyruvate Metabolism |ATAXIA, INTERMITTENT, WITH PYRUVATE DEHYDROGENASE DEFICIENCY |Ataxia, Intermittent, with Pyruvate Dehydrogenase, or Decarboxylase, Deficiency |Ataxia with Lactic Acidosis |Ataxia with Lactic Acidosis I
Slim Mappings:Genetic disease (inborn)|Metabolic disease|Nervous system disease
Reference: MedGen: D015325
MeSH: D015325
OMIM: 312170;
MSeqDR LSDB: 00442;
MSeqDR has 3 matches in descendants: 00046; 00475; 00478;  
Genes: PDHA1;
Phenotypes
1 HP:0001423X-linked dominant inheritance
2 HP:0003593Infantile onset
3 HP:0001999Abnormal facial shape35%
4 HP:0000496Abnormality of eye movement
5 HP:0001274Agenesis of corpus callosum
6 HP:0000463Anteverted nares
7 HP:0002872Apneic episodes precipitated by illness, fatigue, stress
8 HP:0006799Basal ganglia cysts
9 HP:0002059Cerebral atrophy
10 HP:0001266Choreoathetosis
11 HP:0004925Chronic lactic acidosis
12 HP:0002928Decreased activity of the pyruvate dehydrogenase (PDH) complex
13 HP:0001332Dystonia
NAMDC:  Dystonia
14 HP:0002131Episodic ataxia
15 HP:0000454Flared nostrils
16 HP:0002007Frontal bossing
17 HP:0001263Global developmental delay
NAMDC:  Mental retardation
18 HP:0001263Global developmental delay
NAMDC:  Delayed development (evidence of at least one of A through F)
19 HP:0003348Hyperalaninemia
20 HP:0002490Increased CSF lactate
21 HP:0002151Increased serum lactate
22 HP:0001249Intellectual disability
23 HP:0001254Lethargy
24 HP:0000343Long philtrum
25 HP:0000252Microcephaly
26 HP:0001252Muscular hypotonia
NAMDC:  Hypotonia
27 HP:0003812Phenotypic variability
28 HP:0000508Ptosis
NAMDC:  Ptosis
29 HP:0001250Seizures
NAMDC:  Seizures
30 HP:0004900Severe lactic acidosis
31 HP:0001518Small for gestational age
32 HP:0002119Ventriculomegaly
33 HP:0000431Wide nasal bridge
Disease Causing ClinVar Variants
Variation_NameGeneIDGeneSymbolClinicalSignificancedbSNPRCVaccessionTestedInGTRPhenotypeIDsChromosomeStartStopHGVS_cHGVS_pHGVS_gOtherIDsDisease_ClinVar
NM_000284.3(PDHA1):c.29G>C (p.Arg10Pro)5160PDHA1Pathogenic137853257RCV000011634; NMedGen:C1839413,OMIM:312170, Orphanet:ORPHA79243X1936218419362184OMIM Allelic Variant:300502.0017,UniProtKB (protein):P08559#VAR_010238C1839413 312170 Pyruvate dehydrogenase E1-alpha deficiency;
NM_000284.3(PDHA1):c.58-1G>A5160PDHA1Pathogenic-1RCV000688120; NMedGen:C1839413,OMIM:312170, Orphanet:ORPHA79243X1936742919367429-C1839413 312170 Pyruvate dehydrogenase E1-alpha deficiency;
NM_000284.3(PDHA1):c.214C>T (p.Arg72Cys)5160PDHA1Pathogenic/Likely pathogenic863224148RCV000624128; RCV000692713; RCV000505722; NMeSH:D030342,MedGen:C0950123; MedGen:C1839413,OMIM:312170, Orphanet:ORPHA79243; MedGen:CN517202X1936815119368151UniProtKB (protein):P08559#VAR_004949C0950123 Inborn genetic diseases;
NM_000284.3(PDHA1):c.265G>A (p.Gly89Ser)5160PDHA1Uncertain significance-1RCV000680061; NMedGen:C1839413,OMIM:312170, Orphanet:ORPHA79243X1936820219368202-C1839413 312170 Pyruvate dehydrogenase E1-alpha deficiency;
NG_016781.1:g.11219_12516dup5160PDHA1Likely pathogenic-1RCV000735827; NMedGen:C1839413,OMIM:312170, Orphanet:ORPHA79243X1936822919369526-
NM_000284.3(PDHA1):c.292-23A>G5160PDHA1Pathogenic1057518702RCV000415131; NMedGen:C1839413,OMIM:312170, Orphanet:ORPHA79243X1936937619369376-C1839413 312170 Pyruvate dehydrogenase E1-alpha deficiency;
NM_000284.3(PDHA1):c.300_301dup (p.Cys101Serfs)5160PDHA1Likely pathogenic-1RCV000721984; NMedGen:C1839413,OMIM:312170, Orphanet:ORPHA79243X1936940719369408-
NM_000284.3(PDHA1):c.422G>A (p.Arg141Gln)5160PDHA1Pathogenic794729213RCV000184034; NMedGen:C1839413,OMIM:312170, Orphanet:ORPHA79243X1937120319371203-C1839413 312170 Pyruvate dehydrogenase E1-alpha deficiency;
NM_001173455.1(PDHA1):c.448G>A (p.Gly150Arg)5160PDHA1Uncertain significance1057518695RCV000415066; NMedGen:C1839413,OMIM:312170, Orphanet:ORPHA79243X1937120819371208-C1839413 312170 Pyruvate dehydrogenase E1-alpha deficiency;
NM_000284.3(PDHA1):c.434G>A (p.Cys145Tyr)5160PDHA1Uncertain significance1555933946RCV000640507; NMedGen:C1839413,OMIM:312170, Orphanet:ORPHA79243X1937121519371215-C1839413 312170 Pyruvate dehydrogenase E1-alpha deficiency;
NM_000284.3(PDHA1):c.455C>T (p.Ser152Leu)5160PDHA1Likely pathogenic1555933954RCV000578270; NMedGen:C1839413,OMIM:312170, Orphanet:ORPHA79243X1937123619371236-C1839413 312170 Pyruvate dehydrogenase E1-alpha deficiency;
NM_000284.3(PDHA1):c.461A>G (p.His154Arg)5160PDHA1Likely pathogenic1131692230RCV000495894; NMedGen:C1839413,OMIM:312170, Orphanet:ORPHA79243X1937124219371242-C1839413 312170 Pyruvate dehydrogenase E1-alpha deficiency;
NM_000284.3(PDHA1):c.482A>G (p.Tyr161Cys)5160PDHA1Pathogenic-1RCV000679874; NMedGen:C1839413,OMIM:312170, Orphanet:ORPHA79243X1937126319371263-C1839413 312170 Pyruvate dehydrogenase E1-alpha deficiency;
NM_000284.3(PDHA1):c.491A>G (p.Asn164Ser)5160PDHA1Pathogenic1555933963RCV000578359; NMedGen:C1839413,OMIM:312170, Orphanet:ORPHA79243X1937127219371272-C1839413 312170 Pyruvate dehydrogenase E1-alpha deficiency;
NM_000284.3(PDHA1):c.506C>T (p.Ala169Val)5160PDHA1Pathogenic863224150RCV000640506; RCV000199416; NMedGen:C1839413,OMIM:312170, Orphanet:ORPHA79243; MedGen:CN517202X1937128719371287-CN517202 not provided;
NM_000284.3(PDHA1):c.523G>A (p.Ala175Thr)5160PDHA1Pathogenic-1RCV000680062; NMedGen:C1839413,OMIM:312170, Orphanet:ORPHA79243X1937262119372621-C1839413 312170 Pyruvate dehydrogenase E1-alpha deficiency;
NM_000284.3(PDHA1):c.536T>G (p.Leu179Arg)5160PDHA1Likely pathogenic1555934165RCV000578439; NMedGen:C1839413,OMIM:312170, Orphanet:ORPHA79243X1937263419372634-C1839413 312170 Pyruvate dehydrogenase E1-alpha deficiency;
NM_000284.3(PDHA1):c.615C>G (p.Phe205Leu)5160PDHA1Pathogenic137853254RCV000011629; NMedGen:C1839413,OMIM:312170, Orphanet:ORPHA79243X1937347819373478OMIM Allelic Variant:300502.0012,UniProtKB (protein):P08559#VAR_004954C1839413 312170 Pyruvate dehydrogenase E1-alpha deficiency;
NM_000284.3(PDHA1):c.648A>C (p.Leu216Phe)5160PDHA1Pathogenic121917898RCV000011640; NMedGen:C1839413,OMIM:312170, Orphanet:ORPHA79243X1937351119373511OMIM Allelic Variant:300502.0023C1839413 312170 Pyruvate dehydrogenase E1-alpha deficiency;
NM_000284.3(PDHA1):c.727T>A (p.Tyr243Asn)5160PDHA1Pathogenic137853255RCV000011630; NMedGen:C1839413,OMIM:312170, Orphanet:ORPHA79243X1937359019373590OMIM Allelic Variant:300502.0013,UniProtKB (protein):P08559#VAR_021053C1839413 312170 Pyruvate dehydrogenase E1-alpha deficiency;
NM_000284.3(PDHA1):c.759+26G>A5160PDHA1Uncertain significance1555934413RCV000640505; NMedGen:C1839413,OMIM:312170, Orphanet:ORPHA79243X1937364819373648-C1839413 312170 Pyruvate dehydrogenase E1-alpha deficiency;
NM_000284.3(PDHA1):c.773A>C (p.Asp258Ala)5160PDHA1Pathogenic137853253RCV000011628; NMedGen:C1839413,OMIM:312170, Orphanet:ORPHA79243X1937381719373817OMIM Allelic Variant:300502.0011,UniProtKB (protein):P08559#VAR_004958C1839413 312170 Pyruvate dehydrogenase E1-alpha deficiency;
NM_000284.3(PDHA1):c.787C>G (p.Arg263Gly)5160PDHA1Pathogenic137853259RCV000011625; RCV000196576; NMedGen:C1839413,OMIM:312170, Orphanet:ORPHA79243; MedGen:CN517202X1937383119373831OMIM Allelic Variant:300502.0008,UniProtKB (protein):P08559#VAR_004959CN517202 not provided;
NM_001173456.1(PDHA1):c.695_696del (p.Glu233Glyfs)5160PDHA1Likely pathogenic-1RCV000721985; NMedGen:C1839413,OMIM:312170, Orphanet:ORPHA79243X1937383219373833-
NM_000284.3(PDHA1):c.844A>C (p.Met282Leu)5160PDHA1Benign2229137RCV000715720; RCV000011632; RCV000224670; RCV000127400; NMedGen:C2711754; MedGen:C1839413,OMIM:312170, Orphanet:ORPHA79243; MedGen:CN517202; MedGen:CN169374X1937578219375782OMIM Allelic Variant:300502.0015,UniProtKB (protein):P08559#VAR_021054CN517202 not provided;
NM_000284.3(PDHA1):c.861_862insT (p.Arg288Serfs)5160PDHA1Pathogenic606231190RCV000011633; NMedGen:C1839413,OMIM:312170, Orphanet:ORPHA79243X1937579919375800OMIM Allelic Variant:300502.0016C1839413 312170 Pyruvate dehydrogenase E1-alpha deficiency;
NM_000284.3(PDHA1):c.863G>A (p.Arg288His)5160PDHA1Pathogenic137853258RCV000011637; NMedGen:C1839413,OMIM:312170, Orphanet:ORPHA79243X1937580119375801OMIM Allelic Variant:300502.0020,UniProtKB (protein):P08559#VAR_021055C1839413 312170 Pyruvate dehydrogenase E1-alpha deficiency;
NM_000284.3(PDHA1):c.917_918insTAGTTACCGTACACGAGAAGA (p.Glu305_Glu306insAspSerTyrArgThrArgGlu)5160PDHA1Pathogenic606231188RCV000011624; NMedGen:C1839413,OMIM:312170, Orphanet:ORPHA79243X1937703119377051OMIM Allelic Variant:300502.0007C1839413 312170 Pyruvate dehydrogenase E1-alpha deficiency;
NM_000284.3(PDHA1):c.904C>T (p.Arg302Cys)5160PDHA1Pathogenic137853252RCV000622696; RCV000011626; RCV000199671; NMeSH:D030342,MedGen:C0950123; MedGen:C1839413,OMIM:312170, Orphanet:ORPHA79243; MedGen:CN517202X1937703819377038OMIM Allelic Variant:300502.0009,UniProtKB (protein):P08559#VAR_004962C0950123 Inborn genetic diseases;
NM_000284.3(PDHA1):c.910C>T (p.Arg304Ter)5160PDHA1Pathogenic863224146RCV000760291; RCV000196688; NMedGen:C1839413,OMIM:312170, Orphanet:ORPHA79243; MedGen:CN517202X1937704419377044-CN517202 not provided;
NM_000284.3(PDHA1):c.930_932delAAG (p.Arg311del)5160PDHA1Pathogenic1555935223RCV000578365; NMedGen:C1839413,OMIM:312170, Orphanet:ORPHA79243X1937706419377066-C1839413 312170 Pyruvate dehydrogenase E1-alpha deficiency;
NM_000284.3(PDHA1):c.934_940delAGTAAGA (p.Ser312Valfs)5160PDHA1Pathogenic606231185RCV000011619; NMedGen:C1839413,OMIM:312170, Orphanet:ORPHA79243X1937706819377074OMIM Allelic Variant:300502.0002C1839413 312170 Pyruvate dehydrogenase E1-alpha deficiency;
NM_000284.3(PDHA1):c.937_939del (p.Lys313del)5160PDHA1Pathogenic137853251RCV000011621; NMedGen:C1839413,OMIM:312170, Orphanet:ORPHA79243X1937707119377073NC_000023.10:g.19377071_19377073delAAGOMIM Allelic Variant:300502.0004C1839413 312170 Pyruvate dehydrogenase E1-alpha deficiency;
NM_000284.3(PDHA1):c.943G>A (p.Asp315Asn)5160PDHA1Pathogenic137853256RCV000011631; NMedGen:C1839413,OMIM:312170, Orphanet:ORPHA79243X1937707719377077OMIM Allelic Variant:300502.0014,UniProtKB (protein):P08559#VAR_021056C1839413 312170 Pyruvate dehydrogenase E1-alpha deficiency;
NM_000284.3(PDHA1):c.1026_1039del14 (p.Arg343Glyfs)5160PDHA1Pathogenic-1RCV000679875; NMedGen:C1839413,OMIM:312170, Orphanet:ORPHA79243X1937762319377637-C1839413 312170 Pyruvate dehydrogenase E1-alpha deficiency;
NM_000284.3(PDHA1):c.1073_1092del20 (p.Glu358Glyfs)5160PDHA1Pathogenic606231187RCV000011623; NMedGen:C1839413,OMIM:312170, Orphanet:ORPHA79243X1937767119377690OMIM Allelic Variant:300502.0006C1839413 312170 Pyruvate dehydrogenase E1-alpha deficiency;
NM_000284.3(PDHA1):c.1074_1109dup (p.Ser370_Ser371insProProLeuGluGluLeuGlyTyrHisIleTyrSer)5160PDHA1Pathogenic606231191RCV000011636; NMedGen:C1839413,OMIM:312170, Orphanet:ORPHA79243X1937767219377707NC_000023.10:g.19377672_19377707dupOMIM Allelic Variant:300502.0019C1839413 312170 Pyruvate dehydrogenase E1-alpha deficiency;
NM_000284.3(PDHA1):c.1132C>T (p.Arg378Cys)5160PDHA1Pathogenic863224147RCV000497402; RCV000198575; NMedGen:C1839413,OMIM:312170, Orphanet:ORPHA79243; MedGen:CN517202X1937773019377730-CN517202 not provided;
NM_001173454.1(PDHA1):c.1247G>A (p.Arg416His)5160PDHA1Pathogenic137853250RCV000011620; NMedGen:C1839413,OMIM:312170, Orphanet:ORPHA79243X1937773119377731OMIM Allelic Variant:300502.0003,UniProtKB (protein):P08559#VAR_004966C1839413 312170 Pyruvate dehydrogenase E1-alpha deficiency;
NM_000284.3(PDHA1):c.1142_1145dupATCA (p.Trp383Serfs)5160PDHA1Pathogenic606231189RCV000624104; RCV000011627; RCV000199126; NMeSH:D030342,MedGen:C0950123; MedGen:C1839413,OMIM:312170, Orphanet:ORPHA79243; MedGen:CN517202X1937774019377743OMIM Allelic Variant:300502.0010C0950123 Inborn genetic diseases;
NM_000284.3(PDHA1):c.1159_1160delAA (p.Lys387Valfs)5160PDHA1Pathogenic606231186RCV000011622; NMedGen:C1839413,OMIM:312170, Orphanet:ORPHA79243X1937775719377758OMIM Allelic Variant:300502.0005C1839413 312170 Pyruvate dehydrogenase E1-alpha deficiency;
NM_000284.3(PDHA1):c.1167_1170delCAGT (p.Ser390Lysfs)5160PDHA1Pathogenic606231184RCV000011618; NMedGen:C1839413,OMIM:312170, Orphanet:ORPHA79243X1937776519377768OMIM Allelic Variant:300502.0001C1839413 312170 Pyruvate dehydrogenase E1-alpha deficiency;
NM_000284.3(PDHA1):c.*79_*90dup5160PDHA1Pathogenic1555935690RCV000011638; NMedGen:C1839413,OMIM:312170, Orphanet:ORPHA79243X1937785019377861NC_000023.10:g.19377850_19377861dupAGTCAATGAAATOMIM Allelic Variant:300502.0021C1839413 312170 Pyruvate dehydrogenase E1-alpha deficiency;
NM_001135024.1(PDHX):c.88delT (p.Ser30Profs)8050PDHXLikely pathogenic-1RCV000721986; NMedGen:C1839413,OMIM:312170, Orphanet:ORPHA79243113493800634938006-
MSeqDR Portal
Ensembl Gene IDAssociated Gene NameLSDB GenesLSDB VariantsclinVar hitsDescriptionDisease id
ENSG00000131828 MSeqDR Search EnsemblPDHA111243pyruvate dehydrogenase (lipoamide) alpha 1 [Source:HGNC Symbol;Acc:8806]00442

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