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Hello! Guest! Please Login or Register! Clinician Mode

Examples Gene: MT-ND1, POLG, Region: M:1-1000 Variant: m.8993T>G, 1:g.10042757T>C rs3888511 MSCV_0000006, ClinVar: RCV000000015, Disease: Leigh syndrome, Phenotype: Retinopathy

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Most Common: Hearing Loss (D034381), Deafness (D003638), Sensorineural HL (D006319), Waardenburg Syndrome, Usher Syndromes

Disease Browser
Parent Node: Brain Diseases, Metabolic, Inborn (D020739)
Parent Node: Mental Retardation, X-Linked (D038901)
Parent Node: Mitochondrial Diseases (D028361)
Parent Node: Pyruvate Metabolism, Inborn Errors (D015323)
..Starting node ..Pyruvate Dehydrogenase Complex Deficiency Disease (D015325)
Child Nodes:
........Phosphoenolpyruvate carboxykinase 2 deficiency (C536655)
........Pyruvate Dehydrogenase E1-Beta Deficiency (C566729)
........Pyruvate Dehydrogenase E2 Deficiency (C565448)
........Pyruvate Dehydrogenase E3-Binding Protein Deficiency (C565447)
Sister Nodes:
..Leigh Disease (D007888) 12
..Pyruvate Carboxylase Deficiency Disease (D015324) 1
..Pyruvate Dehydrogenase Complex Deficiency Disease (D015325) 4
..Pyruvate Kinase Deficiency of Red Cells (C564858)
Human Disease MESH is developed by UMLS. Further data from MedGen, OMIM, CTD

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;

Genes: PDHA1;

Phenotypes

1	HP:0001423	X-linked dominant inheritance
2	HP:0003593	Infantile onset
3	HP:0001999	Abnormal facial shape	HP:0040284
4	HP:0000496	Abnormality of eye movement
5	HP:0001274	Agenesis of corpus callosum
6	HP:0000463	Anteverted nares
7	HP:0002872	Apneic episodes precipitated by illness, fatigue, stress
8	HP:0006799	Basal ganglia cysts
9	HP:0002059	Cerebral atrophy
10	HP:0001266	Choreoathetosis
11	HP:0004925	Chronic lactic acidosis
12	HP:0002928	Decreased activity of the pyruvate dehydrogenase complex
13	HP:0001332	Dystonia
14	HP:0002131	Episodic ataxia
15	HP:0000454	Flared nostrils
16	HP:0002007	Frontal bossing
17	HP:0001290	Generalized hypotonia
18	HP:0001263	Global developmental delay
19	HP:0003348	Hyperalaninemia
20	HP:0001252	Hypotonia
21	HP:0002490	Increased CSF lactate
22	HP:0002151	Increased serum lactate
23	HP:0001249	Intellectual disability
24	HP:0001254	Lethargy
25	HP:0000343	Long philtrum
26	HP:0000252	Microcephaly
27	HP:0003812	Phenotypic variability
28	HP:0000508	Ptosis
29	HP:0001250	Seizure
30	HP:0004900	Severe lactic acidosis
31	HP:0001518	Small for gestational age
32	HP:0002119	Ventriculomegaly
33	HP:0000431	Wide nasal bridge

Disease Causing ClinVar Variants

Variation_Name	GeneID	GeneSymbol	ClinicalSignificance	dbSNP	RCVaccession	TestedInGTR	PhenotypeIDs	Chromosome	Start	Stop	HGVS_c	HGVS_p	HGVS_g	OtherIDs	Disease_ClinVar
NM_000284.3(PDHA1):c.29G>C (p.Arg10Pro)	5160	PDHA1	Pathogenic	137853257	RCV000011634;	N	MedGen:C1839414,OMIM:312170, Orphanet:ORPHA79243	X	19362184	19362184	NM_000284.3:c.29G>C	NP_000275.1:p.Arg10Pro	NC_000023.10:g.19362184G>C	OMIM Allelic Variant:300502.0017	C1839414 312170 Pyruvate dehydrogenase E1-alpha deficiency
NM_000284.3(PDHA1):c.422G>A (p.Arg141Gln)	5160	PDHA1	Pathogenic	794729213	RCV000184034;	N	MedGen:C1839414,OMIM:312170, Orphanet:ORPHA79243	X	19371203	19371203	NM_000284.3:c.422G>A	NP_000275.1:p.Arg141Gln	NC_000023.10:g.19371203G>A	-	C1839414 312170 Pyruvate dehydrogenase E1-alpha deficiency
NM_000284.3(PDHA1):c.615C>G (p.Phe205Leu)	5160	PDHA1	Pathogenic	137853254	RCV000011629;	N	MedGen:C1839414,OMIM:312170, Orphanet:ORPHA79243	X	19373478	19373478	NM_000284.3:c.615C>G	NP_000275.1:p.Phe205Leu	NC_000023.10:g.19373478C>G	OMIM Allelic Variant:300502.0012	C1839414 312170 Pyruvate dehydrogenase E1-alpha deficiency
NM_000284.3(PDHA1):c.648A>C (p.Leu216Phe)	5160	PDHA1	Pathogenic	121917898	RCV000011640;	N	MedGen:C1839414,OMIM:312170, Orphanet:ORPHA79243	X	19373511	19373511	NM_000284.3:c.648A>C	NP_000275.1:p.Leu216Phe	NC_000023.10:g.19373511A>C	OMIM Allelic Variant:300502.0023	C1839414 312170 Pyruvate dehydrogenase E1-alpha deficiency
NM_000284.3(PDHA1):c.727T>A (p.Tyr243Asn)	5160	PDHA1	Pathogenic	137853255	RCV000011630;	N	MedGen:C1839414,OMIM:312170, Orphanet:ORPHA79243	X	19373590	19373590	NM_000284.3:c.727T>A	NP_000275.1:p.Tyr243Asn	NC_000023.10:g.19373590T>A	OMIM Allelic Variant:300502.0013	C1839414 312170 Pyruvate dehydrogenase E1-alpha deficiency
NM_000284.3(PDHA1):c.773A>C (p.Asp258Ala)	5160	PDHA1	Pathogenic	137853253	RCV000011628;	N	MedGen:C1839414,OMIM:312170, Orphanet:ORPHA79243	X	19373817	19373817	NM_000284.3:c.773A>C	NP_000275.1:p.Asp258Ala	NC_000023.10:g.19373817A>C	OMIM Allelic Variant:300502.0011	C1839414 312170 Pyruvate dehydrogenase E1-alpha deficiency
NM_000284.3(PDHA1):c.787C>G (p.Arg263Gly)	5160	PDHA1	Pathogenic	137853259	RCV000011625; RCV000196576;	N	MedGen:C1839414,OMIM:312170, Orphanet:ORPHA79243; MedGen:CN221809	X	19373831	19373831	NM_000284.3:c.787C>G	NP_000275.1:p.Arg263Gly	NC_000023.10:g.19373831C>G	OMIM Allelic Variant:300502.0008	CN221809 not provided; C1839414 312170 Pyruvate dehydrogenase E1-alpha deficiency
NM_000284.3(PDHA1):c.844A>C (p.Met282Leu)	5160	PDHA1	Benign;Pathogenic	2229137	RCV000011632; RCV000127400;	N	MedGen:C1839414,OMIM:312170, Orphanet:ORPHA79243; MedGen:CN169374	X	19375782	19375782	NM_000284.3:c.844A>C	NP_000275.1:p.Met282Leu	NC_000023.10:g.19375782A>C	OMIM Allelic Variant:300502.0015	CN169374 not specified; C1839414 312170 Pyruvate dehydrogenase E1-alpha deficiency
NM_000284.3(PDHA1):c.861_862insT (p.Arg288Serfs)	5160	PDHA1	Pathogenic	606231190	RCV000011633;	N	MedGen:C1839414,OMIM:312170, Orphanet:ORPHA79243	X	19375799	19375800	NM_000284.3:c.861_862insT	NP_000275.1:p.Arg288Serfs	NC_000023.10:g.19375799_19375800insT	OMIM Allelic Variant:300502.0016	C1839414 312170 Pyruvate dehydrogenase E1-alpha deficiency
NM_000284.3(PDHA1):c.863G>A (p.Arg288His)	5160	PDHA1	Pathogenic	137853258	RCV000011637;	N	MedGen:C1839414,OMIM:312170, Orphanet:ORPHA79243	X	19375801	19375801	NM_000284.3:c.863G>A	NP_000275.1:p.Arg288His	NC_000023.10:g.19375801G>A	OMIM Allelic Variant:300502.0020	C1839414 312170 Pyruvate dehydrogenase E1-alpha deficiency
NM_000284.3(PDHA1):c.900-3_917dup21 (p.Glu305_Glu306insAspSerTyrArgThrArgGlu)	5160	PDHA1	Pathogenic	606231188	RCV000011624;	N	MedGen:C1839414,OMIM:312170, Orphanet:ORPHA79243	X	19377031	19377051	NM_000284.3:c.900-3_917dup21	NP_000275.1:p.Glu305_Glu306insAspSerTyrArgThrArgGlu	NC_000023.10:g.19377031_19377051dup21	OMIM Allelic Variant:300502.0007	C1839414 312170 Pyruvate dehydrogenase E1-alpha deficiency
NM_000284.3(PDHA1):c.904C>T (p.Arg302Cys)	5160	PDHA1	Pathogenic	137853252	RCV000011626; RCV000199671;	N	MedGen:C1839414,OMIM:312170, Orphanet:ORPHA79243; MedGen:CN221809	X	19377038	19377038	NM_000284.3:c.904C>T	NP_000275.1:p.Arg302Cys	NC_000023.10:g.19377038C>T	OMIM Allelic Variant:300502.0009	CN221809 not provided; C1839414 312170 Pyruvate dehydrogenase E1-alpha deficiency
NM_000284.3(PDHA1):c.934_940delAGTAAGA (p.Ser312Valfs)	5160	PDHA1	Pathogenic	606231185	RCV000011619;	N	MedGen:C1839414,OMIM:312170, Orphanet:ORPHA79243	X	19377068	19377074	NM_000284.3:c.934_940delAGTAAGA	NP_000275.1:p.Ser312Valfs	NC_000023.10:g.19377068_19377074delAGTAAGA	OMIM Allelic Variant:300502.0002	C1839414 312170 Pyruvate dehydrogenase E1-alpha deficiency
NM_000284.3(PDHA1):c.937_939delAAG (p.Lys313del)	5160	PDHA1	Pathogenic	137853251	RCV000011621;	N	MedGen:C1839414,OMIM:312170, Orphanet:ORPHA79243	X	19377071	19377073	NM_000284.3:c.937_939delAAG	NP_000275.1:p.Lys313del	NC_000023.10:g.19377071_19377073delAAG	OMIM Allelic Variant:300502.0004	C1839414 312170 Pyruvate dehydrogenase E1-alpha deficiency
NM_000284.3(PDHA1):c.943G>A (p.Asp315Asn)	5160	PDHA1	Pathogenic	137853256	RCV000011631;	N	MedGen:C1839414,OMIM:312170, Orphanet:ORPHA79243	X	19377077	19377077	NM_000284.3:c.943G>A	NP_000275.1:p.Asp315Asn	NC_000023.10:g.19377077G>A	OMIM Allelic Variant:300502.0014	C1839414 312170 Pyruvate dehydrogenase E1-alpha deficiency
NM_000284.3(PDHA1):c.1073_1092del20 (p.Glu358Glyfs)	5160	PDHA1	Pathogenic	606231187	RCV000011623;	N	MedGen:C1839414,OMIM:312170, Orphanet:ORPHA79243	X	19377671	19377690	NM_000284.3:c.1073_1092del20	NP_000275.1:p.Glu358Glyfs	NC_000023.10:g.19377671_19377690del20	OMIM Allelic Variant:300502.0006	C1839414 312170 Pyruvate dehydrogenase E1-alpha deficiency
NM_000284.3(PDHA1):c.1074_1109dup36 (p.Ser370_Ser371insProProLeuGluGluLeuGlyTyrHisIleTyrSer)	5160	PDHA1	Pathogenic	606231191	RCV000011636;	N	MedGen:C1839414,OMIM:312170, Orphanet:ORPHA79243	X	19377672	19377707	NM_000284.3:c.1074_1109dup36	NP_000275.1:p.Ser370_Ser371insProProLeuGluGluLeuGlyTyrHisIleTyrSer	NC_000023.10:g.19377672_19377707dup36	OMIM Allelic Variant:300502.0019	C1839414 312170 Pyruvate dehydrogenase E1-alpha deficiency
NM_000284.3(PDHA1):c.1133G>A (p.Arg378His)	5160	PDHA1	Pathogenic	137853250	RCV000011620;	N	MedGen:C1839414,OMIM:312170, Orphanet:ORPHA79243	X	19377731	19377731	NM_000284.3:c.1133G>A	NP_000275.1:p.Arg378His	NC_000023.10:g.19377731G>A	OMIM Allelic Variant:300502.0003	C1839414 312170 Pyruvate dehydrogenase E1-alpha deficiency
NM_000284.3(PDHA1):c.1142_1145dupATCA (p.Trp383Serfs)	5160	PDHA1	Pathogenic	606231189	RCV000011627; RCV000199126;	N	MedGen:C1839414,OMIM:312170, Orphanet:ORPHA79243; MedGen:CN221809	X	19377740	19377743	NM_000284.3:c.1142_1145dupATCA	NP_000275.1:p.Trp383Serfs	NC_000023.10:g.19377740_19377743dupATCA	OMIM Allelic Variant:300502.0010	CN221809 not provided; C1839414 312170 Pyruvate dehydrogenase E1-alpha deficiency
NM_000284.3(PDHA1):c.1159_1160delAA (p.Lys387Valfs)	5160	PDHA1	Pathogenic	606231186	RCV000011622;	N	MedGen:C1839414,OMIM:312170, Orphanet:ORPHA79243	X	19377757	19377758	NM_000284.3:c.1159_1160delAA	NP_000275.1:p.Lys387Valfs	NC_000023.10:g.19377757_19377758delAA	OMIM Allelic Variant:300502.0005	C1839414 312170 Pyruvate dehydrogenase E1-alpha deficiency
NM_000284.3(PDHA1):c.1167_1170delCAGT (p.Ser390Lysfs)	5160	PDHA1	Pathogenic	606231184	RCV000011618;	N	MedGen:C1839414,OMIM:312170, Orphanet:ORPHA79243	X	19377765	19377768	NM_000284.3:c.1167_1170delCAGT	NP_000275.1:p.Ser390Lysfs	NC_000023.10:g.19377765_19377768delCAGT	OMIM Allelic Variant:300502.0001	C1839414 312170 Pyruvate dehydrogenase E1-alpha deficiency
NM_000284.3(PDHA1):c.79_90dupAGTCAATGAAAT	5160	PDHA1	Pathogenic	606231192	RCV000011638;	N	MedGen:C1839414,OMIM:312170, Orphanet:ORPHA79243	X	19377850	19377861	NM_000284.3:c.79_90dupAGTCAATGAAAT		NC_000023.10:g.19377850_19377861dupAGTCAATGAAAT	OMIM Allelic Variant:300502.0021	C1839414 312170 Pyruvate dehydrogenase E1-alpha deficiency