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:  Delayed development (evidence of at least one of A through F)
18 HP:0001263Global developmental delay
NAMDC:  Mental retardation
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:C1839414,OMIM:312170, Orphanet:ORPHA79243X1936218419362184NM_000284.3:c.29G>CNP_000275.1:p.Arg10ProNC_000023.10:g.19362184G>COMIM Allelic Variant:300502.0017C1839414 312170 Pyruvate dehydrogenase E1-alpha deficiency
NM_000284.3(PDHA1):c.422G>A (p.Arg141Gln)5160PDHA1Pathogenic794729213RCV000184034; NMedGen:C1839414,OMIM:312170, Orphanet:ORPHA79243X1937120319371203NM_000284.3:c.422G>ANP_000275.1:p.Arg141GlnNC_000023.10:g.19371203G>A-C1839414 312170 Pyruvate dehydrogenase E1-alpha deficiency
NM_000284.3(PDHA1):c.615C>G (p.Phe205Leu)5160PDHA1Pathogenic137853254RCV000011629; NMedGen:C1839414,OMIM:312170, Orphanet:ORPHA79243X1937347819373478NM_000284.3:c.615C>GNP_000275.1:p.Phe205LeuNC_000023.10:g.19373478C>GOMIM Allelic Variant:300502.0012C1839414 312170 Pyruvate dehydrogenase E1-alpha deficiency
NM_000284.3(PDHA1):c.648A>C (p.Leu216Phe)5160PDHA1Pathogenic121917898RCV000011640; NMedGen:C1839414,OMIM:312170, Orphanet:ORPHA79243X1937351119373511NM_000284.3:c.648A>CNP_000275.1:p.Leu216PheNC_000023.10:g.19373511A>COMIM Allelic Variant:300502.0023C1839414 312170 Pyruvate dehydrogenase E1-alpha deficiency
NM_000284.3(PDHA1):c.727T>A (p.Tyr243Asn)5160PDHA1Pathogenic137853255RCV000011630; NMedGen:C1839414,OMIM:312170, Orphanet:ORPHA79243X1937359019373590NM_000284.3:c.727T>ANP_000275.1:p.Tyr243AsnNC_000023.10:g.19373590T>AOMIM Allelic Variant:300502.0013C1839414 312170 Pyruvate dehydrogenase E1-alpha deficiency
NM_000284.3(PDHA1):c.773A>C (p.Asp258Ala)5160PDHA1Pathogenic137853253RCV000011628; NMedGen:C1839414,OMIM:312170, Orphanet:ORPHA79243X1937381719373817NM_000284.3:c.773A>CNP_000275.1:p.Asp258AlaNC_000023.10:g.19373817A>COMIM Allelic Variant:300502.0011C1839414 312170 Pyruvate dehydrogenase E1-alpha deficiency
NM_000284.3(PDHA1):c.787C>G (p.Arg263Gly)5160PDHA1Pathogenic137853259RCV000011625; RCV000196576; NMedGen:C1839414,OMIM:312170, Orphanet:ORPHA79243; MedGen:CN221809X1937383119373831NM_000284.3:c.787C>GNP_000275.1:p.Arg263GlyNC_000023.10:g.19373831C>GOMIM Allelic Variant:300502.0008CN221809 not provided; C1839414 312170 Pyruvate dehydrogenase E1-alpha deficiency
NM_000284.3(PDHA1):c.844A>C (p.Met282Leu)5160PDHA1Benign;Pathogenic2229137RCV000011632; RCV000127400; NMedGen:C1839414,OMIM:312170, Orphanet:ORPHA79243; MedGen:CN169374X1937578219375782NM_000284.3:c.844A>CNP_000275.1:p.Met282LeuNC_000023.10:g.19375782A>COMIM Allelic Variant:300502.0015CN169374 not specified; C1839414 312170 Pyruvate dehydrogenase E1-alpha deficiency
NM_000284.3(PDHA1):c.861_862insT (p.Arg288Serfs)5160PDHA1Pathogenic606231190RCV000011633; NMedGen:C1839414,OMIM:312170, Orphanet:ORPHA79243X1937579919375800NM_000284.3:c.861_862insTNP_000275.1:p.Arg288SerfsNC_000023.10:g.19375799_19375800insTOMIM Allelic Variant:300502.0016C1839414 312170 Pyruvate dehydrogenase E1-alpha deficiency
NM_000284.3(PDHA1):c.863G>A (p.Arg288His)5160PDHA1Pathogenic137853258RCV000011637; NMedGen:C1839414,OMIM:312170, Orphanet:ORPHA79243X1937580119375801NM_000284.3:c.863G>ANP_000275.1:p.Arg288HisNC_000023.10:g.19375801G>AOMIM Allelic Variant:300502.0020C1839414 312170 Pyruvate dehydrogenase E1-alpha deficiency
NM_000284.3(PDHA1):c.900-3_917dup21 (p.Glu305_Glu306insAspSerTyrArgThrArgGlu)5160PDHA1Pathogenic606231188RCV000011624; NMedGen:C1839414,OMIM:312170, Orphanet:ORPHA79243X1937703119377051NM_000284.3:c.900-3_917dup21NP_000275.1:p.Glu305_Glu306insAspSerTyrArgThrArgGluNC_000023.10:g.19377031_19377051dup21OMIM Allelic Variant:300502.0007C1839414 312170 Pyruvate dehydrogenase E1-alpha deficiency
NM_000284.3(PDHA1):c.904C>T (p.Arg302Cys)5160PDHA1Pathogenic137853252RCV000011626; RCV000199671; NMedGen:C1839414,OMIM:312170, Orphanet:ORPHA79243; MedGen:CN221809X1937703819377038NM_000284.3:c.904C>TNP_000275.1:p.Arg302CysNC_000023.10:g.19377038C>TOMIM Allelic Variant:300502.0009CN221809 not provided; C1839414 312170 Pyruvate dehydrogenase E1-alpha deficiency
NM_000284.3(PDHA1):c.934_940delAGTAAGA (p.Ser312Valfs)5160PDHA1Pathogenic606231185RCV000011619; NMedGen:C1839414,OMIM:312170, Orphanet:ORPHA79243X1937706819377074NM_000284.3:c.934_940delAGTAAGANP_000275.1:p.Ser312ValfsNC_000023.10:g.19377068_19377074delAGTAAGAOMIM Allelic Variant:300502.0002C1839414 312170 Pyruvate dehydrogenase E1-alpha deficiency
NM_000284.3(PDHA1):c.937_939delAAG (p.Lys313del)5160PDHA1Pathogenic137853251RCV000011621; NMedGen:C1839414,OMIM:312170, Orphanet:ORPHA79243X1937707119377073NM_000284.3:c.937_939delAAGNP_000275.1:p.Lys313delNC_000023.10:g.19377071_19377073delAAGOMIM Allelic Variant:300502.0004C1839414 312170 Pyruvate dehydrogenase E1-alpha deficiency
NM_000284.3(PDHA1):c.943G>A (p.Asp315Asn)5160PDHA1Pathogenic137853256RCV000011631; NMedGen:C1839414,OMIM:312170, Orphanet:ORPHA79243X1937707719377077NM_000284.3:c.943G>ANP_000275.1:p.Asp315AsnNC_000023.10:g.19377077G>AOMIM Allelic Variant:300502.0014C1839414 312170 Pyruvate dehydrogenase E1-alpha deficiency
NM_000284.3(PDHA1):c.1073_1092del20 (p.Glu358Glyfs)5160PDHA1Pathogenic606231187RCV000011623; NMedGen:C1839414,OMIM:312170, Orphanet:ORPHA79243X1937767119377690NM_000284.3:c.1073_1092del20NP_000275.1:p.Glu358GlyfsNC_000023.10:g.19377671_19377690del20OMIM Allelic Variant:300502.0006C1839414 312170 Pyruvate dehydrogenase E1-alpha deficiency
NM_000284.3(PDHA1):c.1074_1109dup36 (p.Ser370_Ser371insProProLeuGluGluLeuGlyTyrHisIleTyrSer)5160PDHA1Pathogenic606231191RCV000011636; NMedGen:C1839414,OMIM:312170, Orphanet:ORPHA79243X1937767219377707NM_000284.3:c.1074_1109dup36NP_000275.1:p.Ser370_Ser371insProProLeuGluGluLeuGlyTyrHisIleTyrSerNC_000023.10:g.19377672_19377707dup36OMIM Allelic Variant:300502.0019C1839414 312170 Pyruvate dehydrogenase E1-alpha deficiency
NM_000284.3(PDHA1):c.1133G>A (p.Arg378His)5160PDHA1Pathogenic137853250RCV000011620; NMedGen:C1839414,OMIM:312170, Orphanet:ORPHA79243X1937773119377731NM_000284.3:c.1133G>ANP_000275.1:p.Arg378HisNC_000023.10:g.19377731G>AOMIM Allelic Variant:300502.0003C1839414 312170 Pyruvate dehydrogenase E1-alpha deficiency
NM_000284.3(PDHA1):c.1142_1145dupATCA (p.Trp383Serfs)5160PDHA1Pathogenic606231189RCV000011627; RCV000199126; NMedGen:C1839414,OMIM:312170, Orphanet:ORPHA79243; MedGen:CN221809X1937774019377743NM_000284.3:c.1142_1145dupATCANP_000275.1:p.Trp383SerfsNC_000023.10:g.19377740_19377743dupATCAOMIM Allelic Variant:300502.0010CN221809 not provided; C1839414 312170 Pyruvate dehydrogenase E1-alpha deficiency
NM_000284.3(PDHA1):c.1159_1160delAA (p.Lys387Valfs)5160PDHA1Pathogenic606231186RCV000011622; NMedGen:C1839414,OMIM:312170, Orphanet:ORPHA79243X1937775719377758NM_000284.3:c.1159_1160delAANP_000275.1:p.Lys387ValfsNC_000023.10:g.19377757_19377758delAAOMIM Allelic Variant:300502.0005C1839414 312170 Pyruvate dehydrogenase E1-alpha deficiency
NM_000284.3(PDHA1):c.1167_1170delCAGT (p.Ser390Lysfs)5160PDHA1Pathogenic606231184RCV000011618; NMedGen:C1839414,OMIM:312170, Orphanet:ORPHA79243X1937776519377768NM_000284.3:c.1167_1170delCAGTNP_000275.1:p.Ser390LysfsNC_000023.10:g.19377765_19377768delCAGTOMIM Allelic Variant:300502.0001C1839414 312170 Pyruvate dehydrogenase E1-alpha deficiency
NM_000284.3(PDHA1):c.*79_*90dupAGTCAATGAAAT5160PDHA1Pathogenic606231192RCV000011638; NMedGen:C1839414,OMIM:312170, Orphanet:ORPHA79243X1937785019377861NM_000284.3:c.*79_*90dupAGTCAATGAAATNC_000023.10:g.19377850_19377861dupAGTCAATGAAATOMIM Allelic Variant:300502.0021C1839414 312170 Pyruvate dehydrogenase E1-alpha deficiency
MSeqDR Portal
Ensembl Gene IDAssociated Gene NameLSDB GenesLSDB VariantsclinVar hitsDescriptionDisease id
ENSG00000131828 MSeqDR Search EnsemblPDHA111222pyruvate dehydrogenase (lipoamide) alpha 1 [Source:HGNC Symbol;Acc:8806]00442

*Click on gene and variants to check details. Or view all variants in new page