PDHAD
MCID: PYR022
MIFTS: 59

Pyruvate Dehydrogenase E1-Alpha Deficiency (PDHAD)

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

Aliases & Classifications for Pyruvate Dehydrogenase E1-Alpha Deficiency

MalaCards integrated aliases for Pyruvate Dehydrogenase E1-Alpha Deficiency:

Name: Pyruvate Dehydrogenase E1-Alpha Deficiency 57 59 74 37 29 13 6 40
Pyruvate Dehydrogenase Complex Deficiency 57 53 25 59 37 29 6
Pyruvate Decarboxylase Deficiency 57 12 53 59 74 15 17
Pyruvate Dehydrogenase Deficiency 12 75 53 25 59 74
Pdh Deficiency 57 53 25 74
Pyruvate Dehydrogenase Complex Deficiency Disease 12 44 72
Pdhad 57 59 74
Ataxia with Lactic Acidosis I 57 74
Pdhc 53 59
Ataxia, Intermittent, with Pyruvate Dehydrogenase, or Decarboxylase, Deficiency 53
Ataxia Intermittent with Pyruvate Dehydrogenase or Decarboxylase Deficiency 74
Pyruvate Dehydrogenase Complex E1 Component Subunit Alpha Deficiency 59
Ataxia, Intermittent, with Pyruvate Dehydrogenase Deficiency 57
Intermittent Ataxia with Pyruvate Dehydrogenase Deficiency 25
Ataxia, Intermittent, with Abnormal Pyruvate Metabolism 57
Ataxia Intermittent with Abnormal Pyruvate Metabolism 74
Pyruvate Dehydrogenase E1 Alpha Deficiency 72
Deficiency of Pyruvic Dehydrogenase 12
Ataxia with Lactic Acidosis 1 53
Ataxia with Lactic Acidosis 25
Pdhc Deficiency 25
Pdc Deficiency 53
Pdh 59

Characteristics:

Orphanet epidemiological data:

59
pyruvate dehydrogenase e1-alpha deficiency
Inheritance: X-linked dominant; Age of onset: Infancy,Neonatal; Age of death: adolescent,late childhood;
pyruvate dehydrogenase deficiency
Inheritance: Autosomal recessive,Not applicable,X-linked dominant; Prevalence: <1/1000000 (Europe); Age of onset: Childhood,Infancy,Neonatal; Age of death: adolescent,late childhood;

OMIM:

57
Miscellaneous:
highly variable phenotype
onset in infancy or early childhood
two main phenotypes, metabolic and neurologic
35% of patients have facial dysmorphism
a subset of patients improve with thiamine
severe infantile cases usually die by 6 months
females demonstrate lyonization with corresponding phenotypic variation

Inheritance:
x-linked dominant


HPO:

32
pyruvate dehydrogenase e1-alpha deficiency:
Onset and clinical course infantile onset
Inheritance x-linked dominant inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:3649
MeSH 44 D015325
NCIt 50 C103968
SNOMED-CT 68 46683007
ICD10 33 E74.4
MESH via Orphanet 45 C536257 D015325
ICD10 via Orphanet 34 E74.4
UMLS via Orphanet 73 C0034345 C1839413 C2936911
UMLS 72 C0034345 C1839413

Summaries for Pyruvate Dehydrogenase E1-Alpha Deficiency

NIH Rare Diseases : 53 Pyruvate dehydrogenase complex (PDC) deficiency is a type of metabolic disease. This means that the body is not able to efficiently break down nutrients in food to be used for energy. Symptoms of PDC deficiency include signs of metabolic dysfunction such as extreme tiredness (lethargy), poor feeding, and rapid breathing (tachypnea). Other symptoms may include signs of neurological dysfunction such as developmental delay, periods of uncontrolled movements (ataxia), low muscle tone (hypotonia), abnormal eye movements, and seizures. Symptoms usually begin in infancy, but signs can first appear at birth or later in childhood. Symptoms may be especially apparent during times of illness, stress, or after meals with high amounts of carbohydrates. The most common form of PDC deficiency is caused by genetic changes (mutations or pathogenic variants) in the PDHA1 gene. These pathogenic variants are inherited in an X-linked manner. Pathogenic variants in other genes including PDHB, DLAT, PDHX, DLD, and PDP1 can also cause PDC deficiency. These pathogenic variants are inherited in an autosomal recessive manner. PDC deficiency is diagnosed based on laboratory tests including blood tests, analysis of the urine, and brain MRI. The diagnosis can be confirmed by analyzing the pyruvate dehydrogenase enzyme. Treatment for PDC deficiency includes dietary supplementation with carnitine, thiamine, and lipoic acid.

MalaCards based summary : Pyruvate Dehydrogenase E1-Alpha Deficiency, also known as pyruvate dehydrogenase complex deficiency, is related to lactic acidosis and pyruvate dehydrogenase e3-binding protein deficiency, and has symptoms including seizures, lethargy and nasal flaring. An important gene associated with Pyruvate Dehydrogenase E1-Alpha Deficiency is PDHA1 (Pyruvate Dehydrogenase E1 Alpha 1 Subunit), and among its related pathways/superpathways are Pyruvate metabolism and Glycolysis / Gluconeogenesis. The drugs Strawberry and pyruvate have been mentioned in the context of this disorder. Affiliated tissues include brain, testes and eye, and related phenotypes are muscular hypotonia and feeding difficulties in infancy

Disease Ontology : 12 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 : 25 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 : 57 Genetic defects in the pyruvate dehydrogenase complex are one of the most common causes of primary lactic acidosis in children. Most cases are caused by mutation in the E1-alpha subunit gene on the X chromosome. X-linked PDH deficiency is one of the few X-linked diseases in which a high proportion of heterozygous females manifest severe symptoms. The clinical spectrum of PDH deficiency is broad, ranging from fatal lactic acidosis in the newborn to chronic neurologic dysfunction with structural abnormalities in the central nervous system without systemic acidosis (Robinson et al., 1987; Brown et al., 1994). (312170)

KEGG : 37
Pyruvate dehydrogenase complex deficiency is an autosomal or X-linked recessive disorder caused by deficient enzyme activity in the pyruvate dehydrogenase complex, resulting in deficiency of acetyl CoA and reduced synthesis of acetylcholine. This deficiency in newborns may lead to brain malformations. The PDH complex comprises three catalytic subunits, PDH (E1), dihydrolipoamide acetyltransferase (E2) and dihydrolipoamide dehydrogenase (E3), and two regulatory subunits, E1 kinase and phospho-E1-phosphatase, together with a sixth component, E3-binding protein, which is believed to play a role in the attachment of E3 to the E2 core.

UniProtKB/Swiss-Prot : 74 Pyruvate dehydrogenase E1-alpha deficiency: An enzymatic defect causing primary lactic acidosis in children. It is associated with a broad clinical spectrum ranging from fatal lactic acidosis in the newborn to chronic neurologic dysfunction with structural abnormalities in the central nervous system without systemic acidosis.

Wikipedia : 75 Pyruvate dehydrogenase deficiency (also known as pyruvate dehydrogenase complex deficiency or PDCD) is... more...

Related Diseases for Pyruvate Dehydrogenase E1-Alpha Deficiency

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

(show top 50) (show all 113)
# Related Disease Score Top Affiliating Genes
1 lactic acidosis 30.6 PDHX PDHA1
2 pyruvate dehydrogenase e3-binding protein deficiency 30.2 PDHX PDHA1
3 leigh syndrome 29.2 PDHX PDHB PDHA1 ECHS1
4 mitochondrial metabolism disease 28.9 PDHA1 HIBCH ECHS1
5 pyruvate carboxylase deficiency 11.9
6 pyruvate dehydrogenase e1-beta deficiency 11.9
7 pyruvate dehydrogenase e2 deficiency 11.7
8 alpha-ketoglutarate dehydrogenase deficiency 11.4
9 leigh syndrome, french canadian type 11.4
10 pyruvate dehydrogenase phosphatase deficiency 11.4
11 encephalopathy 10.3
12 hypotonia 10.3
13 ataxia and polyneuropathy, adult-onset 10.3
14 hydrocephalus, congenital, 1 10.2
15 west syndrome 10.2
16 inherited metabolic disorder 10.2
17 nuclear gene-encoded leigh syndrome 10.2
18 neuropathy 10.2
19 glucose transporter type 1 deficiency syndrome 10.2
20 myoclonus 10.2
21 hepatocellular carcinoma 10.2
22 primary biliary cirrhosis 10.2
23 ischemia 10.2
24 primary biliary cholangitis 10.2
25 hypoxia 10.2
26 ocular motor apraxia 10.1
27 kearns-sayre syndrome 10.1
28 microcephaly 10.1
29 mitochondrial disorders 10.1
30 hyper-beta-alaninemia 10.1
31 alacrima, achalasia, and mental retardation syndrome 10.1
32 alcohol-related neurodevelopmental disorder 10.1
33 optic nerve disease 10.1
34 movement disease 10.1
35 peripheral nervous system disease 10.1
36 diabetes mellitus, noninsulin-dependent 10.0
37 systemic lupus erythematosus 10.0
38 muscular dystrophy, duchenne type 10.0
39 oral squamous cell carcinoma 10.0
40 glucose intolerance 10.0
41 pneumocystosis 10.0
42 cryptococcosis 10.0
43 esophageal candidiasis 10.0
44 candidiasis 10.0
45 histoplasmosis 10.0
46 squamous cell carcinoma 10.0
47 dental caries 10.0
48 leptospirosis 10.0
49 liver cirrhosis 10.0
50 thyroiditis 10.0

Graphical network of the top 20 diseases related to Pyruvate Dehydrogenase E1-Alpha Deficiency:



Diseases related to Pyruvate Dehydrogenase E1-Alpha Deficiency

Symptoms & Phenotypes for Pyruvate Dehydrogenase E1-Alpha Deficiency

Human phenotypes related to Pyruvate Dehydrogenase E1-Alpha Deficiency:

59 32 (show top 50) (show all 53)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 muscular hypotonia 59 32 hallmark (90%) Very frequent (99-80%) HP:0001252
2 feeding difficulties in infancy 59 32 hallmark (90%) Very frequent (99-80%) HP:0008872
3 lethargy 59 32 hallmark (90%) Very frequent (99-80%) HP:0001254
4 abnormality of eye movement 59 32 frequent (33%) Frequent (79-30%) HP:0000496
5 seizures 59 32 frequent (33%) Frequent (79-30%) HP:0001250
6 ataxia 59 32 frequent (33%) Frequent (79-30%) HP:0001251
7 spasticity 59 32 frequent (33%) Frequent (79-30%) HP:0001257
8 dysarthria 59 32 frequent (33%) Frequent (79-30%) HP:0001260
9 gait disturbance 59 32 frequent (33%) Frequent (79-30%) HP:0001288
10 tremor 59 32 frequent (33%) Frequent (79-30%) HP:0001337
11 abnormal pyramidal sign 59 32 frequent (33%) Frequent (79-30%) HP:0007256
12 global developmental delay 59 32 frequent (33%) Frequent (79-30%) HP:0001263
13 microcephaly 59 32 frequent (33%) Frequent (79-30%) HP:0000252
14 intrauterine growth retardation 59 32 frequent (33%) Frequent (79-30%) HP:0001511
15 choreoathetosis 59 32 frequent (33%) Frequent (79-30%) HP:0001266
16 aplasia/hypoplasia of the corpus callosum 59 32 frequent (33%) Frequent (79-30%) HP:0007370
17 tachypnea 59 32 frequent (33%) Frequent (79-30%) HP:0002789
18 osteolytic defects of the middle phalanx of the 4th toe 59 32 frequent (33%) Frequent (79-30%) HP:0100453
19 hypertelorism 59 32 occasional (7.5%) Occasional (29-5%) HP:0000316
20 pectus excavatum 59 32 occasional (7.5%) Occasional (29-5%) HP:0000767
21 frontal bossing 59 32 occasional (7.5%) Occasional (29-5%) HP:0002007
22 high palate 59 32 occasional (7.5%) Occasional (29-5%) HP:0000218
23 wide nasal bridge 59 32 occasional (7.5%) Occasional (29-5%) HP:0000431
24 dyspnea 59 32 occasional (7.5%) Occasional (29-5%) HP:0002094
25 long philtrum 59 32 occasional (7.5%) Occasional (29-5%) HP:0000343
26 epicanthus 59 32 occasional (7.5%) Occasional (29-5%) HP:0000286
27 dystonia 59 32 occasional (7.5%) Occasional (29-5%) HP:0001332
28 multiple lipomas 59 32 occasional (7.5%) Occasional (29-5%) HP:0001012
29 ventriculomegaly 59 32 occasional (7.5%) Occasional (29-5%) HP:0002119
30 trigonocephaly 59 32 occasional (7.5%) Occasional (29-5%) HP:0000243
31 narrow face 59 32 occasional (7.5%) Occasional (29-5%) HP:0000275
32 upslanted palpebral fissure 59 32 occasional (7.5%) Occasional (29-5%) HP:0000582
33 cerebral palsy 59 32 occasional (7.5%) Occasional (29-5%) HP:0100021
34 abnormal facial shape 59 32 very rare (1%) Very frequent (99-80%) HP:0001999
35 agenesis of corpus callosum 32 HP:0001274
36 ptosis 32 HP:0000508
37 intellectual disability 32 HP:0001249
38 anteverted nares 32 HP:0000463
39 generalized hypotonia 32 HP:0001290
40 growth delay 59 Very frequent (99-80%)
41 increased serum lactate 32 HP:0002151
42 increased csf lactate 32 HP:0002490
43 cerebral atrophy 32 HP:0002059
44 hyperalaninemia 32 HP:0003348
45 small for gestational age 32 HP:0001518
46 episodic ataxia 32 HP:0002131
47 severe lactic acidosis 32 HP:0004900
48 decreased activity of the pyruvate dehydrogenase complex 32 HP:0002928
49 basal ganglia cysts 32 HP:0006799
50 flared nostrils 32 HP:0000454

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Face:
frontal bossing
long philtrum

Head And Neck Nose:
wide nasal bridge
flared nostrils
upturned nose

Growth Weight:
low birth weight

Metabolic Features:
lactic acidosis, severe
lactic acidosis, chronic
a subset of patients may have subtle increases in blood lactate
a subset of patients may have normal levels of blood lactate

Neurologic Central Nervous System:
seizures
dystonia
choreoathetosis
lethargy
cerebral atrophy
more
Head And Neck Head:
microcephaly
narrow head

Head And Neck Eyes:
abnormal eye movements
episodic ptosis

Laboratory Abnormalities:
increased blood pyruvic acid
increased blood lactic acid
increased csf pyruvic acid
increased csf lactic acid
increased blood alanine
more

Clinical features from OMIM:

312170

UMLS symptoms related to Pyruvate Dehydrogenase E1-Alpha Deficiency:


seizures, lethargy, nasal flaring

Drugs & Therapeutics for Pyruvate Dehydrogenase E1-Alpha Deficiency

Drugs for Pyruvate Dehydrogenase E1-Alpha Deficiency (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Strawberry Approved Phase 3
2 pyruvate Phase 3
3 4-phenylbutyric acid Phase 1, Phase 2
4 Pharmaceutical Solutions Phase 1

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Phase 3 Trial of Dichloroacetate in Pyruvate Dehydrogenase Complex Deficiency: Recruiting NCT02616484 Phase 3 Dichloroacetate (DCA)
2 Pilot Clinical Trial to Investigate the Safety and Efficacy of Phenylbutyrate Therapy for Patients With Pyruvate Dehydrogenase Complex Deficiency. Recruiting NCT03734263 Phase 1, Phase 2 sodium phenylbutyrate
3 A Pilot Study of Rapid Haplotyping Procedure for Personalized Dosing of Dichloroacetate (DCA) in Healthy Volunteers Part 1: Rapid Haplotyping Procedure for Determining the Response of Patients to DCA. Part 2: Personalized Dosing of Dichloroacetate for the Treatment of Rare and Common Diseases Completed NCT02690285 Phase 1 Dichloroacetate (DCA)
4 Natural History and Advanced Genetic Study of Pyruvate Dehydrogenase Complex Deficiencies (North American Mitochondrial Disease Consortium, Rare Diseases Clinical Research Network, Project 7413) Recruiting NCT03056794
5 VIVE Mind: Terapias Corpo-mente Nos Cuidados de saúde primários - Estudo Aleatorizado e Controlado Not yet recruiting NCT04058119
6 VIVE Active: avaliação de um Programa de Treino Funcional Nos Cuidados de saúde primários - Estudo Quasi-experimental Not yet recruiting NCT04058093

Search NIH Clinical Center for Pyruvate Dehydrogenase E1-Alpha Deficiency

Cochrane evidence based reviews: pyruvate dehydrogenase complex deficiency disease

Genetic Tests for Pyruvate Dehydrogenase E1-Alpha Deficiency

Genetic tests related to Pyruvate Dehydrogenase E1-Alpha Deficiency:

# Genetic test Affiliating Genes
1 Pyruvate Dehydrogenase E1-Alpha Deficiency 29 PDHA1
2 Pyruvate Dehydrogenase Complex Deficiency 29

Anatomical Context for Pyruvate Dehydrogenase E1-Alpha Deficiency

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

41
Brain, Testes, Eye, Cortex, Liver, Skin, Bone

Publications for Pyruvate Dehydrogenase E1-Alpha Deficiency

Articles related to Pyruvate Dehydrogenase E1-Alpha Deficiency:

(show top 50) (show all 180)
# Title Authors PMID Year
1
Cerebral palsy and pyruvate dehydrogenase deficiency: identification of two new mutations in the E1alpha gene. 38 8 71
10486093 1999
2
Pyruvate dehydrogenase E1 alpha deficiency in a family: different clinical presentation in two siblings. 38 8 71
9686362 1998
3
An amino acid substitution in the pyruvate dehydrogenase E1 alpha gene, affecting mitochondrial import of the precursor protein. 38 8 71
7573035 1995
4
A mutation in the E1 alpha subunit of pyruvate dehydrogenase associated with variable expression of pyruvate dehydrogenase complex deficiency. 38 8 71
1508605 1992
5
Thiamine-responsive pyruvate dehydrogenase deficiency in two patients caused by a point mutation (F205L and L216F) within the thiamine pyrophosphate binding region. 8 71
12379317 2002
6
Biochemical and molecular analysis of an X-linked case of Leigh syndrome associated with thiamin-responsive pyruvate dehydrogenase deficiency. 8 71
9266390 1997
7
Pyruvate dehydrogenase deficiency. Clinical presentation and molecular genetic characterization of five new patients. 8 71
8032855 1994
8
Pyruvate dehydrogenase deficiency in a male caused by a point mutation (F205L) in the E1 alpha subunit. 8 71
8199595 1994
9
Defective gene in lactic acidosis: abnormal pyruvate dehydrogenase E1 alpha-subunit caused by a frame shift. 8 71
2537010 1989
10
A deficiency of both subunits of pyruvate dehydrogenase which is not expressed in fibroblasts. 8 71
3137520 1988
11
Pyruvate dehydrogenase E1 alpha deficiency: males and females differ yet again. 38 71
7887408 1995
12
Characterization of the mutations in three patients with pyruvate dehydrogenase E1 alpha deficiency. 38 71
1909401 1991
13
Fatal lactic acidosis due to deficiency of E1 component of the pyruvate dehydrogenase complex. 38 8
3139934 1988
14
Pyruvate dehydrogenase complex-E2 deficiency causes paroxysmal exercise-induced dyskinesia. 71
29093066 2017
15
Dihydrolipoamide Dehydrogenase Deficiency 71
25032271 2014
16
Stimulation of reactive oxygen species generation by disease-causing mutations of lipoamide dehydrogenase. 71
21558426 2011
17
Cryptic proteolytic activity of dihydrolipoamide dehydrogenase. 71
17404228 2007
18
Novel mutations in dihydrolipoamide dehydrogenase deficiency in two cousins with borderline-normal PDH complex activity. 71
16770810 2006
19
Somatic mosaicism in a male with an exon skipping mutation in PDHA1 of the pyruvate dehydrogenase complex results in a milder phenotype. 8
16412675 2006
20
Clinical and genetic spectrum of pyruvate dehydrogenase deficiency: dihydrolipoamide acetyltransferase (E2) deficiency. 71
16049940 2005
21
A novel mutation in the dihydrolipoamide dehydrogenase E3 subunit gene (DLD) resulting in an atypical form of alpha-ketoglutarate dehydrogenase deficiency. 71
15712224 2005
22
Mutations in the gene for the E1beta subunit: a novel cause of pyruvate dehydrogenase deficiency. 71
15138885 2004
23
Leigh syndrome due to compound heterozygosity of dihydrolipoamide dehydrogenase gene mutations. Description of the first E3 splice site mutation. 71
12925875 2003
24
Differential effect of DCA treatment on the pyruvate dehydrogenase complex in patients with severe PDHC deficiency. 8
12621116 2003
25
Identification of a common mutation (Gly194Cys) in both Arab Moslem and Ashkenazi Jewish patients with dihydrolipoamide dehydrogenase (E3) deficiency: possible beneficial effect of vitamin therapy. 71
14765544 2003
26
Novel mutations in a boy with dihydrolipoamide dehydrogenase deficiency. 71
11687750 2001
27
Lipoamide dehydrogenase deficiency due to a novel mutation in the interface domain. 71
10448086 1999
28
Molecular basis of lipoamide dehydrogenase deficiency in Ashkenazi Jews. 71
9934985 1999
29
Thiamine-responsive lactic acidaemia: role of pyruvate dehydrogenase complex. 8
9727848 1998
30
Arginine 302 mutations in the pyruvate dehydrogenase E1alpha subunit gene: identification of further patients and in vitro demonstration of pathogenicity. 71
9671272 1998
31
Transfection screening for primary defects in the pyruvate dehydrogenase E1alpha subunit gene. 8
9259285 1997
32
Lipoamide dehydrogenase deficiency in Ashkenazi Jews: an insertion mutation in the mitochondrial leader sequence. 71
9298831 1997
33
Identification of two mutations in a compound heterozygous child with dihydrolipoamide dehydrogenase deficiency. 71
8968745 1996
34
Leigh disease with deficiency of lipoamide dehydrogenase: treatment failure with dichloroacetate. 71
8652022 1996
35
Association of cerebral dysgenesis and lactic acidemia with X-linked PDH E1 alpha subunit mutations in females. 71
8771169 1995
36
Pyruvate dehydrogenase deficiency. 8
7853374 1994
37
Cerebral dysgenesis and lactic acidemia: an MRI/MRS phenotype associated with pyruvate dehydrogenase deficiency. 8
7880337 1994
38
Molecular analysis of abnormal pyruvate dehydrogenase in a patient with thiamine-responsive congenital lactic acidemia. 8
7808831 1994
39
Neurodevelopmental abnormalities and lactic acidosis in a girl with a 20-bp deletion in the X-linked pyruvate dehydrogenase E1 alpha subunit gene. 71
7692352 1993
40
Molecular genetic characterization of an X-linked form of Leigh's syndrome. 8
8498846 1993
41
Identification of two missense mutations in a dihydrolipoamide dehydrogenase-deficient patient. 71
8506365 1993
42
Mutations in the X-linked E1 alpha subunit of pyruvate dehydrogenase leading to deficiency of the pyruvate dehydrogenase complex. 71
8504306 1993
43
A four-nucleotide insertion hotspot in the X chromosome located pyruvate dehydrogenase E1 alpha gene (PDHA1). 71
8504309 1993
44
Alpha-ketoglutarate dehydrogenase deficiency presenting as congenital lactic acidosis. 71
1640293 1992
45
X-linked pyruvate dehydrogenase E1 alpha subunit deficiency in heterozygous females: variable manifestation of the same mutation. 8
1293379 1992
46
Mutations and polymorphisms in the pyruvate dehydrogenase E1 alpha gene. 8
1301207 1992
47
Mutation of E1 alpha gene in a female patient with pyruvate dehydrogenase deficiency due to rapid degradation of E1 protein. 71
1338114 1992
48
Pyruvate dehydrogenase deficiency due to a 20-bp deletion in exon II of the pyruvate dehydrogenase (PDH) E1 alpha gene. 71
1907799 1991
49
Demonstration of an unstable variant of pyruvate dehydrogenase protein (E1) in cultured fibroblasts from a patient with congenital lactic acidemia. 71
1909778 1991
50
Pyruvate dehydrogenase deficiency due to a mutation of the E1 alpha subunit. 71
1770778 1991

Variations for Pyruvate Dehydrogenase E1-Alpha Deficiency

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

6 (show top 50) (show all 237)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 PDHA1 NM_000284.4(PDHA1): c.482A> G (p.Tyr161Cys) single nucleotide variant Pathogenic X:19371263-19371263 X:19353145-19353145
2 PDHA1 NM_000284.4(PDHA1): c.523G> A (p.Ala175Thr) single nucleotide variant Pathogenic X:19372621-19372621 X:19354503-19354503
3 PDHA1 NM_000284.4(PDHA1): c.1026_1039del (p.Arg343fs) deletion Pathogenic X:19377623-19377637 X:19359506-19359519
4 PDHA1 NM_000284.4(PDHA1): c.1163_1166CAGT[1] (p.Ser390fs) short repeat Pathogenic rs606231184 X:19377765-19377768 X:19359647-19359650
5 PDHA1 NM_000284.4(PDHA1): c.927_933AGTAAGA[1] (p.Ser312fs) short repeat Pathogenic rs606231185 X:19377068-19377074 X:19358950-19358956
6 PDHA1 NM_000284.4(PDHA1): c.1133G> A (p.Arg378His) single nucleotide variant Pathogenic rs137853250 X:19377731-19377731 X:19359613-19359613
7 PDHA1 NM_000284.4(PDHA1): c.938_940del (p.Lys313del) deletion Pathogenic rs137853251 X:19377071-19377073 X:19358953-19358955
8 PDHA1 NM_000284.4(PDHA1): c.1159_1160del (p.Lys387fs) deletion Pathogenic rs606231186 X:19377757-19377758 X:19359639-19359640
9 PDHA1 NM_000284.4(PDHA1): c.1073_1092del (p.Glu358fs) deletion Pathogenic rs606231187 X:19377671-19377690 X:19359553-19359572
10 PDHA1 NM_000284.3(PDHA1) insertion Pathogenic rs606231188 X:19377031-19377051 X:19358913-19358933
11 PDHA1 NM_000284.4(PDHA1): c.787C> G (p.Arg263Gly) single nucleotide variant Pathogenic rs137853259 X:19373831-19373831 X:19355713-19355713
12 PDHA1 NM_000284.4(PDHA1): c.904C> T (p.Arg302Cys) single nucleotide variant Pathogenic rs137853252 X:19377038-19377038 X:19358920-19358920
13 PDHA1 NM_000284.4(PDHA1): c.1142_1145dup (p.Trp383fs) duplication Pathogenic rs606231189 X:19377740-19377743 X:19359622-19359625
14 PDHA1 NM_000284.4(PDHA1): c.773A> C (p.Asp258Ala) single nucleotide variant Pathogenic rs137853253 X:19373817-19373817 X:19355699-19355699
15 PDHA1 NM_000284.4(PDHA1): c.615C> G (p.Phe205Leu) single nucleotide variant Pathogenic rs137853254 X:19373478-19373478 X:19355360-19355360
16 PDHA1 NM_000284.4(PDHA1): c.727T> A (p.Tyr243Asn) single nucleotide variant Pathogenic rs137853255 X:19373590-19373590 X:19355472-19355472
17 PDHA1 NM_000284.4(PDHA1): c.943G> A (p.Asp315Asn) single nucleotide variant Pathogenic rs137853256 X:19377077-19377077 X:19358959-19358959
18 PDHA1 NM_000284.4(PDHA1): c.292-23A> G single nucleotide variant Pathogenic rs1057518702 X:19369376-19369376 X:19351258-19351258
19 PDHA1 NM_000284.4(PDHA1): c.930_932AAG[1] (p.Arg311del) short repeat Pathogenic rs1555935223 X:19377064-19377066 X:19358946-19358948
20 PDHA1 NM_000284.4(PDHA1): c.861_862insT (p.Arg288fs) insertion Pathogenic rs606231190 X:19375799-19375800 X:19357681-19357682
21 PDHA1 NM_000284.4(PDHA1): c.29G> C (p.Arg10Pro) single nucleotide variant Pathogenic rs137853257 X:19362184-19362184 X:19344066-19344066
22 PDHA1 PDHA1, 13-BP INS, EX10 insertion Pathogenic
23 PDHA1 NM_000284.4(PDHA1): c.1074_1109dup (p.Pro359_Ser370dup) duplication Pathogenic rs606231191 X:19377672-19377707 X:19359554-19359589
24 PDHA1 NM_000284.4(PDHA1): c.863G> A (p.Arg288His) single nucleotide variant Pathogenic rs137853258 X:19375801-19375801 X:19357683-19357683
25 PDHA1 NM_000284.3(PDHA1): c.*79_*90dup duplication Pathogenic rs1555935690 X:19377850-19377861 X:19359732-19359743
26 PDHA1 NM_000284.4(PDHA1): c.648A> C (p.Leu216Phe) single nucleotide variant Pathogenic rs121917898 X:19373511-19373511 X:19355393-19355393
27 PDHA1 NM_000284.4(PDHA1): c.491A> G (p.Asn164Ser) single nucleotide variant Pathogenic rs1555933963 X:19371272-19371272 X:19353154-19353154
28 PDHA1 NM_000284.4(PDHA1): c.506C> T (p.Ala169Val) single nucleotide variant Pathogenic rs863224150 X:19371287-19371287 X:19353169-19353169
29 PDHA1 NM_000284.4(PDHA1): c.910C> T (p.Arg304Ter) single nucleotide variant Pathogenic rs863224146 X:19377044-19377044 X:19358926-19358926
30 PDHA1 NM_000284.4(PDHA1): c.1132C> T (p.Arg378Cys) single nucleotide variant Pathogenic rs863224147 X:19377730-19377730 X:19359612-19359612
31 PDHA1 NM_000284.4(PDHA1): c.422G> A (p.Arg141Gln) single nucleotide variant Pathogenic rs794729213 X:19371203-19371203 X:19353085-19353085
32 PDHA1 NM_000284.4(PDHA1): c.58-1G> A single nucleotide variant Pathogenic X:19367429-19367429 X:19349311-19349311
33 PDHA1 NM_000284.4(PDHA1): c.225G> T (p.Glu75Asp) single nucleotide variant Pathogenic X:19368162-19368162 X:19350044-19350044
34 PDHA1 NM_000284.4(PDHA1) duplication Pathogenic X:19377067-19377068 X:19358950-19359008
35 PDHA1 NM_000284.4(PDHA1): c.214C> T (p.Arg72Cys) single nucleotide variant Pathogenic/Likely pathogenic rs863224148 X:19368151-19368151 X:19350033-19350033
36 PDHA1 NM_000284.4(PDHA1): c.536T> G (p.Leu179Arg) single nucleotide variant Likely pathogenic rs1555934165 X:19372634-19372634 X:19354516-19354516
37 PDHA1 NM_000284.4(PDHA1): c.1050_1133dup (p.Gln351_Arg378dup) duplication Likely pathogenic rs1555935486 X:19377648-19377731 X:19359530-19359613
38 PDHA1 NM_000284.4(PDHA1): c.461A> G (p.His154Arg) single nucleotide variant Likely pathogenic rs1131692230 X:19371242-19371242 X:19353124-19353124
39 PDHA1 NM_000284.4(PDHA1): c.455C> T (p.Ser152Leu) single nucleotide variant Likely pathogenic rs1555933954 X:19371236-19371236 X:19353118-19353118
40 PDHA1 NM_000284.4(PDHA1): c.749C> T (p.Pro250Leu) single nucleotide variant Likely pathogenic X:19373612-19373612 X:19355494-19355494
41 PDHX NM_001135024.1(PDHX): c.88delT deletion Likely pathogenic 11:34938006-34938006 11:34916459-34916459
42 PDHA1 NM_000284.4(PDHA1): c.300_301dup (p.Cys101fs) duplication Likely pathogenic X:19369407-19369408 X:19351289-19351290
43 PDHA1 NM_000284.4(PDHA1): c.789_790AG[1] (p.Glu264fs) short repeat Likely pathogenic X:19373832-19373833 X:19355714-19355715
44 PDHA1 NM_000284.4(PDHA1): c.291+1_418+1dup duplication Likely pathogenic X:19368229-19369526 X:19350111-19351408
45 PDHX NM_003477.3(PDHX): c.474G> A (p.Glu158=) single nucleotide variant Conflicting interpretations of pathogenicity rs148723565 11:34979062-34979062 11:34957515-34957515
46 PDHX NM_003477.3(PDHX): c.161-6T> C single nucleotide variant Conflicting interpretations of pathogenicity rs200438675 11:34952945-34952945 11:34931398-34931398
47 DLAT NM_001931.4(DLAT): c.506+12G> A single nucleotide variant Conflicting interpretations of pathogenicity rs372355218 11:111899375-111899375 11:112028651-112028651
48 DLAT NM_001931.4(DLAT): c.828G> T (p.Leu276=) single nucleotide variant Conflicting interpretations of pathogenicity rs199835215 11:111908037-111908037 11:112037313-112037313
49 DLAT NM_001931.4(DLAT): c.946C> T (p.Pro316Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs149088081 11:111908155-111908155 11:112037431-112037431
50 DLAT NM_001931.4(DLAT): c.55G> C (p.Glu19Gln) single nucleotide variant Conflicting interpretations of pathogenicity rs61757217 11:111896251-111896251 11:112025527-112025527

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

74 (show all 20)
# Symbol AA change Variation ID SNP ID
1 PDHA1 p.Arg72Cys VAR_004949 rs863224148
2 PDHA1 p.His113Asp VAR_004950
3 PDHA1 p.Gly162Arg VAR_004951 rs866868610
4 PDHA1 p.Val167Met VAR_004952
5 PDHA1 p.Ala199Thr VAR_004953
6 PDHA1 p.Phe205Leu VAR_004954 rs137853254
7 PDHA1 p.Met210Val VAR_004955 rs794727843
8 PDHA1 p.Pro217Leu VAR_004956 rs113169179
9 PDHA1 p.Thr231Ala VAR_004957
10 PDHA1 p.Asp258Ala VAR_004958 rs137853253
11 PDHA1 p.Arg263Gly VAR_004959 rs137853259
12 PDHA1 p.Arg263Gln VAR_004960
13 PDHA1 p.His292Leu VAR_004961
14 PDHA1 p.Arg302Cys VAR_004962 rs137853252
15 PDHA1 p.Arg302His VAR_004963 rs106479414
16 PDHA1 p.Arg378His VAR_004966 rs137853250
17 PDHA1 p.Arg10Pro VAR_010238 rs137853257
18 PDHA1 p.Tyr243Asn VAR_021053 rs137853255
19 PDHA1 p.Arg288His VAR_021055 rs137853258
20 PDHA1 p.Asp315Asn VAR_021056 rs137853256

Expression for Pyruvate Dehydrogenase E1-Alpha Deficiency

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

Pathways for Pyruvate Dehydrogenase E1-Alpha Deficiency

Pathways related to Pyruvate Dehydrogenase E1-Alpha Deficiency according to KEGG:

37
# Name Kegg Source Accession
1 Pyruvate metabolism hsa00620
2 Glycolysis / Gluconeogenesis hsa00010

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

(show all 16)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.65 PDHX PDHB PDHA1 LIPT1 HIBCH ECHS1
2
Show member pathways
13.29 PDHX PDHB PDHA1 LIPT1 HIBCH
3
Show member pathways
12.21 PDHX PDHB PDHA1
4
Show member pathways
11.63 HIBCH ECHS1
5
Show member pathways
11.61 PDHX PDHB PDHA1
6
Show member pathways
11.58 PDHB PDHA1 HIBCH ECHS1
7 11.57 PDHB PDHA1
8
Show member pathways
11.55 PDHB PDHA1
9 11.55 PDHB PDHA1
10 11.39 PDHX PDHA1 HIBCH
11 11.32 PDHB PDHA1
12
Show member pathways
11.15 PDHX PDHB PDHA1
13
Show member pathways
11.06 PDHB PDHA1
14
Show member pathways
10.96 HIBCH ECHS1
15 10.9 HIBCH ECHS1
16
Show member pathways
10.54 PDHX PDHB PDHA1 LIPT1

GO Terms for Pyruvate Dehydrogenase E1-Alpha Deficiency

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

# Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 9.7 PDHX PDHB PDHA1 LONP1 LIPT1 HIBCH
2 mitochondrial matrix GO:0005759 9.17 PDHX PDHB PDHA1 LONP1 LIPT1 HIBCH
3 pyruvate dehydrogenase complex GO:0045254 9.13 PDHX PDHB PDHA1

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

# Name GO ID Score Top Affiliating Genes
1 glucose metabolic process GO:0006006 9.32 PDHB PDHA1
2 fatty acid beta-oxidation GO:0006635 9.26 HIBCH ECHS1
3 tricarboxylic acid cycle GO:0006099 9.16 PDHB PDHA1
4 acetyl-CoA biosynthetic process from pyruvate GO:0006086 8.96 PDHB PDHA1
5 mitochondrial acetyl-CoA biosynthetic process from pyruvate GO:0061732 8.8 PDHX PDHB PDHA1

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

# Name GO ID Score Top Affiliating Genes
1 pyruvate dehydrogenase (acetyl-transferring) activity GO:0004739 9.16 PDHB PDHA1
2 pyruvate dehydrogenase activity GO:0004738 8.96 PDHB PDHA1
3 pyruvate dehydrogenase (NAD+) activity GO:0034604 8.8 PDHX PDHB PDHA1

Sources for Pyruvate Dehydrogenase E1-Alpha Deficiency

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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