MCID: PYR022
MIFTS: 47

Pyruvate Dehydrogenase E1-Alpha Deficiency malady

Genetic diseases, Rare diseases, Neuronal diseases, Metabolic diseases, Fetal diseases categories

Summaries for Pyruvate Dehydrogenase E1-Alpha Deficiency

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NIH Rare Diseases:41 Pyruvate dehydrogenase deficiency is metabolic disorder associated with abnormal function of the mitochondria in cells, thus depriving the body of energy. progressive neurological symptoms usually start in infancy but may be evident at birth, or in later childhood; these symptoms may include developmental delay, intermittent ataxia, poor muscle tone (hypotonia), abnormal eye movements, or seizures. severe lethargy, poor feeding, and tachypnea (rapid breathing) commonly occur, especially during times of illness, stress, or high carbohydrate intake. childhood-onset forms of the condition are often associated with intermittent periods of illness but normal neurological development. prognosis is difficult to predict due to the many causes of the condition, but in most cases of neonatal and infantile onset, prognosis is described as poor. the most common form of pyruvate dehydrogenase deficiency is caused by mutations in the e1 alpha gene, and is inherited in an x-linked dominant manner; all other forms are caused by various genes and are inherited in an autosomal recessive manner. in addition to directly treating acidosis and providing alternative energy for the body, treatment typically includes dietary supplementation with thiamine, carnitine, and lipoic acids, although not all individuals respond to this therapy. last updated: 1/4/2011

MalaCards based summary: Pyruvate Dehydrogenase E1-Alpha Deficiency, also known as pyruvate dehydrogenase complex deficiency, is related to lactic acidosis and leigh syndrome, and has symptoms including muscular hypotonia, reduced consciousness/confusion and feeding difficulties in infancy. An important gene associated with Pyruvate Dehydrogenase E1-Alpha Deficiency is PDHA1 (pyruvate dehydrogenase (lipoamide) alpha 1), and among its related pathways are Glycolysis and gluconeogenesis short map and Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.. The compounds 2-oxo acid and dihydrolipoamide have been mentioned in the context of this disorder. Affiliated tissues include eye, brain and cortex.

Disease Ontology:9 A carbohydrate metabolic disorder characterized by the buildup of lactic acid in the body and a variety of neurological problems and caused by a deficiency of one of the three enzymes in the pyruvate dehydrogenase complex.

Genetics Home Reference:21 Pyruvate dehydrogenase deficiency is characterized by the buildup of a chemical called lactic acid in the body and a variety of neurological problems. Signs and symptoms of this condition usually first appear shortly after birth, and they can vary widely among affected individuals. The most common feature is a potentially life-threatening buildup of lactic acid (lactic acidosis), which can cause nausea, vomiting, severe breathing problems, and an abnormal heartbeat. People with pyruvate dehydrogenase deficiency usually have neurological problems as well. Most have delayed development of mental abilities and motor skills such as sitting and walking. Other neurological problems can include intellectual disability, seizures, weak muscle tone (hypotonia), poor coordination, and difficulty walking. Some affected individuals have abnormal brain structures, such as underdevelopment of the tissue connecting the left and right halves of the brain (corpus callosum), wasting away (atrophy) of the exterior part of the brain known as the cerebral cortex, or patches of damaged tissue (lesions) on some parts of the brain. Because of the severe health effects, many individuals with pyruvate dehydrogenase deficiency do not survive past childhood, although some may live into adolescence or adulthood.

OMIM:45 Genetic defects in the pyruvate dehydrogenase complex are one of the most common causes of primary lactic acidosis in... (312170) more...

Wikipedia:63 Pyruvate dehydrogenase deficiency (also known as pyruvate dehydrogenase complex deficiency or PDCD) is... more...

Aliases & Classifications for Pyruvate Dehydrogenase E1-Alpha Deficiency

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Sources:
45OMIM, 9Disease Ontology, 10diseasecard, 41NIH Rare Diseases, 20GeneTests, 21Genetics Home Reference, 11DISEASES, 47Orphanet, 22GTR, 60UMLS, 55SNOMED-CT, 33MeSH, 27ICD9CM, 34MESH via Orphanet, 26ICD10 via Orphanet, 61UMLS via Orphanet, 25ICD10
See all sources

Pyruvate Dehydrogenase E1-Alpha Deficiency, Aliases & Descriptions:

Name: Pyruvate Dehydrogenase E1-Alpha Deficiency 45 10 20 47 22
Pyruvate Dehydrogenase Complex Deficiency 41 20 21 47 22
Pyruvate Decarboxylase Deficiency 9 41 11 47 60
Pyruvate Dehydrogenase Deficiency 9 41 21 47 60
Pyruvate Dehydrogenase Complex Deficiency Disease 9 60
Pdhc 41 47
Pdh 41 47
Ataxia, Intermittent, with Pyruvate Dehydrogenase, or Decarboxylase, Deficiency 41
Pyruvate Dehydrogenase Complex E1 Component Subunit Alpha Deficiency 47
 
Intermittent Ataxia with Pyruvate Dehydrogenase Deficiency 21
Pyruvate Dehydrogenase E1 Alpha Deficiency 60
Deficiency of Pyruvic Dehydrogenase 9
Ataxia with Lactic Acidosis, Type I 60
Ataxia with Lactic Acidosis 1 41
Ataxia with Lactic Acidosis 21
Pdhc Deficiency 21
Pdh Deficiency 21
Pdhad 47


Classifications:



Characteristics (Orphanet epidemiological data):

47
pyruvate dehydrogenase complex deficiency:
Inheritance: Autosomal recessive,Not applicable,X-linked dominant; Age of onset: Childhood,Infancy,Neonatal; Age of death: adolescent,late childhood
pyruvate dehydrogenase e1-alpha deficiency:
Inheritance: X-linked dominant; Age of onset: Infancy,Neonatal; Age of death: adolescent,late childhood


External Ids:

OMIM45 312170
Disease Ontology9 DOID:3649
MeSH33 D015325
ICD9CM27 271.8
Orphanet47 765, 79243
MESH via Orphanet34 C536257, D015325
ICD10 via Orphanet26 E74.4
UMLS via Orphanet61 C0034345, C2936911
ICD1025 R27.0

Related Diseases for Pyruvate Dehydrogenase E1-Alpha Deficiency

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Diseases related to Pyruvate Dehydrogenase E1-Alpha Deficiency via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 19)
idRelated DiseaseScoreTop Affiliating Genes
1lactic acidosis30.8PDHX, PDHA1
2leigh syndrome30.2PDHX, PDHA1
3primary biliary cirrhosis29.7PDHX, PDP1
4pyruvate carboxylase deficiency10.7
5pyruvate dehydrogenase e2 deficiency10.5
6west syndrome10.5
7pyruvate dehydrogenase phosphatase deficiency10.3
8ataxia10.2
9cerebritis10.2
10periventricular leukomalacia10.2
11dystonia10.2
12spinocerebellar degeneration10.2
13leukomalacia10.2
14ischemia10.2
15hypoxia10.2
16breast cancer10.0
17dihydrolipoamide dehydrogenase deficiency10.0
18lacticacidemia due to pdx1 deficiency10.0
19galactosemia9.9PDHX, PDP1

Graphical network of diseases related to Pyruvate Dehydrogenase E1-Alpha Deficiency:



Diseases related to pyruvate dehydrogenase e1-alpha deficiency

Symptoms for Pyruvate Dehydrogenase E1-Alpha Deficiency

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Symptoms by clinical synopsis from OMIM:

312170

Clinical features from OMIM:

312170

Symptoms:

 47 (show all 38)
  • facial dysmorphism
  • feeding disorder/dysphagia/swallowing/sucking disorder/esophageal dyskinesia
  • motor deficit/trouble
  • hypotonia
  • obnubilation/coma/lethargia/desorientation
  • autosomal recessive inheritance
  • x-linked dominant inheritance
  • failure to thrive/difficulties for feeding in infancy/growth delay
  • microcephaly
  • abnormal eye movements/oculomotor disorder
  • respiratory rhythm disorder
  • corpus callosum/septum pellucidum total/partial agenesis
  • abnormal gait
  • ataxia/incoordination/trouble of the equilibrium
  • tremor
  • chorea/athetosis/choreoathetosis/choreic syndrome
  • pyramidal syndrome
  • hypertonia/spasticity/rigidity/stiffness
  • seizures/epilepsy/absences/spasms/status epilepticus
  • elocution disorders/dysarthria/dysphonia
  • intellectual deficit/mental/psychomotor retardation/learning disability
  • intrauterine growth retardation
  • trigonocephaly
  • frontal bossing/prominent forehead
  • narrow face
  • hypertelorism
  • upslanted palpebral fissures/mongoloid slanting palpebral fissures
  • epicanthic folds
  • broad nose/nasal bridge
  • long philtrum
  • high vaulted/narrow palate
  • pectus excavatum
  • xanthomas/lipomas
  • respiratory distress/dyspnea/respiratory failure/lung volume reduction
  • dilated cerebral ventricles without hydrocephaly
  • dystonia/torticollis/writer's cramp/blepharospasms
  • acute palsy
  • early death/lethality

HPO human phenotypes related to Pyruvate Dehydrogenase E1-Alpha Deficiency:

(show all 62)
id Description Frequency HPO Source Accession
1 muscular hypotonia hallmark (90%) HP:0001252
2 reduced consciousness/confusion hallmark (90%) HP:0004372
3 feeding difficulties in infancy hallmark (90%) HP:0008872
4 microcephaly typical (50%) HP:0000252
5 abnormality of eye movement typical (50%) HP:0000496
6 seizures typical (50%) HP:0001250
7 hypertonia typical (50%) HP:0001276
8 gait disturbance typical (50%) HP:0001288
9 tremor typical (50%) HP:0001337
10 intrauterine growth retardation typical (50%) HP:0001511
11 chorea typical (50%) HP:0002072
12 neurological speech impairment typical (50%) HP:0002167
13 incoordination typical (50%) HP:0002311
14 abnormal pattern of respiration typical (50%) HP:0002793
15 aplasia/hypoplasia of the corpus callosum typical (50%) HP:0007370
16 cognitive impairment typical (50%) HP:0100543
17 abnormal facial shape 35% HP:0001999
18 abnormality of the palate occasional (7.5%) HP:0000174
19 trigonocephaly occasional (7.5%) HP:0000243
20 narrow face occasional (7.5%) HP:0000275
21 epicanthus occasional (7.5%) HP:0000286
22 hypertelorism occasional (7.5%) HP:0000316
23 long philtrum occasional (7.5%) HP:0000343
24 abnormality of the nose occasional (7.5%) HP:0000366
25 upslanted palpebral fissure occasional (7.5%) HP:0000582
26 pectus excavatum occasional (7.5%) HP:0000767
27 multiple lipomas occasional (7.5%) HP:0001012
28 frontal bossing occasional (7.5%) HP:0002007
29 respiratory insufficiency occasional (7.5%) HP:0002093
30 ventriculomegaly occasional (7.5%) HP:0002119
31 cerebral palsy occasional (7.5%) HP:0100021
32 microcephaly HP:0000252
33 long philtrum HP:0000343
34 wide nasal bridge HP:0000431
35 flared nostrils HP:0000454
36 anteverted nares HP:0000463
37 abnormality of eye movement HP:0000496
38 ptosis HP:0000508
39 intellectual disability HP:0001249
40 seizures HP:0001250
41 muscular hypotonia HP:0001252
42 lethargy HP:0001254
43 global developmental delay HP:0001263
44 choreoathetosis HP:0001266
45 agenesis of corpus callosum HP:0001274
46 dystonia HP:0001332
47 x-linked dominant inheritance HP:0001423
48 small for gestational age HP:0001518
49 frontal bossing HP:0002007
50 cerebral atrophy HP:0002059
51 ventriculomegaly HP:0002119
52 episodic ataxia HP:0002131
53 increased serum lactate HP:0002151
54 increased csf lactate HP:0002490
55 apneic episodes precipitated by illness, fatigue, stress HP:0002872
56 decreased activity of the pyruvate dehydrogenase (pdh) complex HP:0002928
57 hyperalaninemia HP:0003348
58 infantile onset HP:0003593
59 phenotypic variability HP:0003812
60 severe lactic acidosis HP:0004900
61 chronic lactic acidosis HP:0004925
62 basal ganglia cysts HP:0006799

Drugs & Therapeutics for Pyruvate Dehydrogenase E1-Alpha Deficiency

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Drug clinical trials:

Search ClinicalTrials for Pyruvate Dehydrogenase E1-Alpha Deficiency

Search NIH Clinical Center for Pyruvate Dehydrogenase E1-Alpha Deficiency

Genetic Tests for Pyruvate Dehydrogenase E1-Alpha Deficiency

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Genetic tests related to Pyruvate Dehydrogenase E1-Alpha Deficiency:

id Genetic test Affiliating Genes
1 Pyruvate Dehydrogenase Complex Deficiency20 22
2 Pyruvate Dehydrogenase E1-Alpha Deficiency20 22 PDHA1

Anatomical Context for Pyruvate Dehydrogenase E1-Alpha Deficiency

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MalaCards organs/tissues related to Pyruvate Dehydrogenase E1-Alpha Deficiency:

31
Eye, Brain, Cortex, Lung

Animal Models for Pyruvate Dehydrogenase E1-Alpha Deficiency or affiliated genes

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Publications for Pyruvate Dehydrogenase E1-Alpha Deficiency

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Variations for Pyruvate Dehydrogenase E1-Alpha Deficiency

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UniProtKB/Swiss-Prot genetic disease variations for Pyruvate Dehydrogenase E1-Alpha Deficiency:

62 (show all 20)
id Symbol AA change Variation ID SNP ID
1PDHA1p.Arg72CysVAR_004949
2PDHA1p.His113AspVAR_004950
3PDHA1p.Gly162ArgVAR_004951
4PDHA1p.Val167MetVAR_004952
5PDHA1p.Ala199ThrVAR_004953
6PDHA1p.Phe205LeuVAR_004954
7PDHA1p.Met210ValVAR_004955
8PDHA1p.Pro217LeuVAR_004956
9PDHA1p.Thr231AlaVAR_004957
10PDHA1p.Asp258AlaVAR_004958
11PDHA1p.Arg263GlyVAR_004959rs28936081
12PDHA1p.Arg263GlnVAR_004960
13PDHA1p.His292LeuVAR_004961
14PDHA1p.Arg302CysVAR_004962
15PDHA1p.Arg302HisVAR_004963
16PDHA1p.Arg378HisVAR_004966
17PDHA1p.Arg10ProVAR_010238
18PDHA1p.Tyr243AsnVAR_021053
19PDHA1p.Arg288HisVAR_021055
20PDHA1p.Asp315AsnVAR_021056rs28935187

Clinvar genetic disease variations for Pyruvate Dehydrogenase E1-Alpha Deficiency:

6 (show all 12)
id Gene Variation Type Significance SNP ID Assembly Location
1PDHXPDHX, 85-BP DEL, NT78deletionPathogenic
2PDHXPDHX, 59-BP DEL, NT965deletionPathogenic
3PDHXPDHX, 4-BP DEL, 125GAAGdeletionPathogenic
4PDHXPDHX, IVS5DS, G-Asingle nucleotide variantPathogenic
5PDHXPDHX, IVS8AS, G-A, -1single nucleotide variantPathogenic
6PDHXPDHX, 1-BP DEL, 620CdeletionPathogenic
7PDHXPDHX, 46-KB DELdeletionPathogenic
8PDHXNM_003477.2(PDHX): c.742C> T (p.Gln248Ter)single nucleotide variantPathogenicrs113309941GRCh37Chr 11, 34988287: 34988287
9PDHXPDHX, 3,913-BP DELdeletionPathogenic
10PDHXNM_003477.2(PDHX): c.44G> A (p.Arg15His)single nucleotide variantPathogenicrs387906998GRCh37Chr 11, 34938246: 34938246
11PDP1PDP1, 3-BP DEL, LEU213deletionPathogenic
12PDP1NM_018444.3(PDP1): c.277G> T (p.Glu93Ter)single nucleotide variantPathogenicrs267606938GRCh37Chr 8, 94934564: 94934564

Expression for genes affiliated with Pyruvate Dehydrogenase E1-Alpha Deficiency

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Search GEO for disease gene expression data for Pyruvate Dehydrogenase E1-Alpha Deficiency.

Pathways for genes affiliated with Pyruvate Dehydrogenase E1-Alpha Deficiency

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Pathways related to Pyruvate Dehydrogenase E1-Alpha Deficiency according to GeneCards Suite gene sharing:

idSuper pathways (with members indented)ScoreTop Affiliating Genes
1
Show member pathways
glycolysis36
gluconeogenesis36
Glycolysis and Gluconeogenesis36
9.3PDHX, PDHA1
2
Show member pathways
8.5PDHA1, PDP1, PDHX
3
Show member pathways
TCA cycle36
pyruvate decarboxylation to acetyl CoA36
NAD phosphorylation and dephosphorylation36
TCA Cycle36
conversion of glucose to acetyl CoA and entry into the TCA cycle36
8.5PDP1, PDHA1, PDHX
4
Show member pathways
8.5PDHA1, PDHX, PDP1

Compounds for genes affiliated with Pyruvate Dehydrogenase E1-Alpha Deficiency

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Sources:
43Novoseek, 24HMDB, 12DrugBank, 28IUPHAR
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Compounds related to Pyruvate Dehydrogenase E1-Alpha Deficiency according to GeneCards Suite gene sharing:

(show all 17)
idCompoundScoreTop Affiliating Genes
12-oxo acid439.4PDHX, PDP1
2dihydrolipoamide43 2410.4PDP1, PDHX
3alpha lipoic acid439.4PDP1, PDHX
4alpha-ketoglutarate439.3PDP1, PDHX
5lipoamide43 2410.3PDHA1, PDP1
6dichloroacetate439.3PDHA1, PDP1
7acetyl-l-carnitine439.3PDHA1, PDP1
8thiamine pyrophosphate43 2410.3PDHA1, PDP1
9carnitine439.2PDHA1, PDP1
10citrate439.1PDP1, PDHA1
11acetyl-coa43 2410.1PDP1, PDHA1
12nadh43 24 1211.0PDP1, PDHA1
13adp43 28 2411.0PDP1, PDHA1
14glycogen43 249.9PDHA1, PDP1
15pyruvate438.8PDHX, PDHA1, PDP1
16lactate438.7PDP1, PDHA1
17glucose438.7PDHA1, PDHX, PDP1

GO Terms for genes affiliated with Pyruvate Dehydrogenase E1-Alpha Deficiency

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Cellular components related to Pyruvate Dehydrogenase E1-Alpha Deficiency according to GeneCards Suite gene sharing:

idNameGO IDScoreTop Affiliating Genes
1mitochondrial matrixGO:00057598.5PDP1, PDHA1, PDHX

Biological processes related to Pyruvate Dehydrogenase E1-Alpha Deficiency according to GeneCards Suite gene sharing:

idNameGO IDScoreTop Affiliating Genes
1regulation of acetyl-CoA biosynthetic process from pyruvateGO:00105108.5PDP1, PDHA1, PDHX
2small molecule metabolic processGO:00442818.5PDP1, PDHA1, PDHX
3pyruvate metabolic processGO:00060908.4PDP1, PDHA1, PDHX
4cellular metabolic processGO:00442378.2PDHX, PDHA1, PDP1

Products for genes affiliated with Pyruvate Dehydrogenase E1-Alpha Deficiency

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  • Antibodies
  • Proteins
  • Lysates
  • Antibodies
  • Proteins
  • Kits and Assays

Sources for Pyruvate Dehydrogenase E1-Alpha Deficiency

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3CDC
13ExPASy
14FMA
22GTR
23HGMD
24HMDB
25ICD10
26ICD10 via Orphanet
27ICD9CM
28IUPHAR
29KEGG
33MeSH
34MESH via Orphanet
35MGI
38NCIt
39NDF-RT
42NINDS
43Novoseek
45OMIM
46OMIM via Orphanet
50PubMed
51QIAGEN
56SNOMED-CT via Orphanet
60UMLS
61UMLS via Orphanet