PDHAD
MCID: PYR022
MIFTS: 62

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 56 58 73 36 29 13 6 39
Pyruvate Dehydrogenase Complex Deficiency 56 52 25 58 36 29 6
Pyruvate Decarboxylase Deficiency 56 12 52 58 73 15 17
Pyruvate Dehydrogenase Deficiency 12 74 52 25 58 73
Pdh Deficiency 56 52 25 73
Pyruvate Dehydrogenase Complex Deficiency Disease 12 43 71
Pdhad 56 58 73
Ataxia with Lactic Acidosis I 56 73
Pdhc 52 58
Pdh 52 58
Ataxia, Intermittent, with Pyruvate Dehydrogenase, or Decarboxylase, Deficiency 52
Ataxia Intermittent with Pyruvate Dehydrogenase or Decarboxylase Deficiency 73
Pyruvate Dehydrogenase Complex E1 Component Subunit Alpha Deficiency 58
Ataxia, Intermittent, with Pyruvate Dehydrogenase Deficiency 56
Intermittent Ataxia with Pyruvate Dehydrogenase Deficiency 25
Ataxia, Intermittent, with Abnormal Pyruvate Metabolism 56
Ataxia Intermittent with Abnormal Pyruvate Metabolism 73
Pyruvate Dehydrogenase E1 Alpha Deficiency 71
Deficiency of Pyruvic Dehydrogenase 12
Ataxia with Lactic Acidosis 1 52
Ataxia with Lactic Acidosis 25
Pdhc Deficiency 25
Pdc Deficiency 52

Characteristics:

Orphanet epidemiological data:

58
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:

56
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:

31
pyruvate dehydrogenase e1-alpha deficiency:
Onset and clinical course infantile onset
Inheritance x-linked dominant inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism
Developmental anomalies during embryogenesis


Summaries for Pyruvate Dehydrogenase E1-Alpha Deficiency

NIH Rare Diseases : 52 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 pyruvate dehydrogenase e3-binding protein deficiency and lactic acidosis, and has symptoms including seizures, lethargy and nasal flaring. An important gene associated with Pyruvate Dehydrogenase E1-Alpha Deficiency is PDHA1 (Pyruvate Dehydrogenase E1 Subunit Alpha 1), 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 : 56 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 : 36 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 : 73 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 : 74 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 130)
# Related Disease Score Top Affiliating Genes
1 pyruvate dehydrogenase e3-binding protein deficiency 30.8 PDHX PDHA1
2 lactic acidosis 30.2 POLG PDHX PDHB PDHA1 PC NFU1
3 aceruloplasminemia 29.9 SLC2A1 POLG PC H2AC18
4 dystonia 29.3 SUOX SLC2A1 SLC19A3 POLG PDHA1 LIPT1
5 leigh syndrome 29.1 SUOX SLC19A3 POLG PDHX PDHB PDHA1
6 mitochondrial metabolism disease 28.1 SUOX SLC19A3 POLG PDHX PDHB PDHA1
7 pyruvate carboxylase deficiency 11.9
8 pyruvate dehydrogenase e1-beta deficiency 11.9
9 pyruvate dehydrogenase e2 deficiency 11.7
10 alpha-ketoglutarate dehydrogenase deficiency 11.4
11 leigh syndrome, french canadian type 11.4
12 pyruvate dehydrogenase phosphatase deficiency 11.4
13 hypotonia 10.3
14 biotin deficiency 10.3 SLC19A3 PC H2AC18
15 ataxia and polyneuropathy, adult-onset 10.3
16 encephalopathy 10.3
17 autoimmune disease of urogenital tract 10.3 PDHX H2AC18 DLAT
18 hyperlysinemia, type i 10.3 SUOX PC
19 mitochondrial dna depletion syndrome 9 10.2 SLC19A3 POLG PDHA1
20 fanconi anemia, complementation group i 10.2 POLG H2AC18
21 hydrocephalus, congenital, 1 10.2
22 west syndrome 10.2
23 inherited metabolic disorder 10.2
24 nuclear gene-encoded leigh syndrome 10.2
25 propionic acidemia 10.2 PC HIBCH ECHS1
26 neuropathy 10.2
27 multiple carboxylase deficiency 10.2 SUOX PC H2AC18
28 biotinidase deficiency 10.2 SUOX PC HIBCH
29 glucose transporter type 1 deficiency syndrome 10.2
30 myoclonus 10.2
31 cerebral creatine deficiency syndrome 2 10.2 SUOX POLG
32 acyl-coa dehydrogenase deficiency 10.2 PC ETFDH
33 hepatocellular carcinoma 10.2
34 primary biliary cirrhosis 10.2
35 ischemia 10.2
36 hypoxia 10.2
37 alpha-methylacetoacetic aciduria 10.1 HIBCH ETFDH ECHS1
38 kearns-sayre syndrome 10.1
39 microcephaly 10.1
40 mitochondrial disorders 10.1
41 ocular motor apraxia 10.1
42 carnitine deficiency, systemic primary 10.1 PC ETFDH
43 leigh syndrome with leukodystrophy 10.1 SLC19A3 PDHA1 LIPT1 ECHS1
44 hyper-beta-alaninemia 10.1
45 alacrima, achalasia, and mental retardation syndrome 10.1
46 alcohol-related neurodevelopmental disorder 10.1
47 periventricular leukomalacia 10.1
48 optic nerve disease 10.1
49 movement disease 10.1
50 peripheral nervous system disease 10.1

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:

58 31 (show top 50) (show all 53)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 muscular hypotonia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001252
2 feeding difficulties in infancy 58 31 hallmark (90%) Very frequent (99-80%) HP:0008872
3 lethargy 58 31 hallmark (90%) Very frequent (99-80%) HP:0001254
4 seizures 58 31 frequent (33%) Frequent (79-30%) HP:0001250
5 spasticity 58 31 frequent (33%) Frequent (79-30%) HP:0001257
6 abnormal pyramidal sign 58 31 frequent (33%) Frequent (79-30%) HP:0007256
7 abnormality of eye movement 58 31 frequent (33%) Frequent (79-30%) HP:0000496
8 ataxia 58 31 frequent (33%) Frequent (79-30%) HP:0001251
9 dysarthria 58 31 frequent (33%) Frequent (79-30%) HP:0001260
10 gait disturbance 58 31 frequent (33%) Frequent (79-30%) HP:0001288
11 tremor 58 31 frequent (33%) Frequent (79-30%) HP:0001337
12 global developmental delay 58 31 frequent (33%) Frequent (79-30%) HP:0001263
13 intrauterine growth retardation 58 31 frequent (33%) Frequent (79-30%) HP:0001511
14 microcephaly 58 31 frequent (33%) Frequent (79-30%) HP:0000252
15 choreoathetosis 58 31 frequent (33%) Frequent (79-30%) HP:0001266
16 aplasia/hypoplasia of the corpus callosum 58 31 frequent (33%) Frequent (79-30%) HP:0007370
17 tachypnea 58 31 frequent (33%) Frequent (79-30%) HP:0002789
18 osteolytic defects of the middle phalanx of the 4th toe 58 31 frequent (33%) Frequent (79-30%) HP:0100453
19 hypertelorism 58 31 occasional (7.5%) Occasional (29-5%) HP:0000316
20 pectus excavatum 58 31 occasional (7.5%) Occasional (29-5%) HP:0000767
21 frontal bossing 58 31 occasional (7.5%) Occasional (29-5%) HP:0002007
22 high palate 58 31 occasional (7.5%) Occasional (29-5%) HP:0000218
23 wide nasal bridge 58 31 occasional (7.5%) Occasional (29-5%) HP:0000431
24 dyspnea 58 31 occasional (7.5%) Occasional (29-5%) HP:0002094
25 long philtrum 58 31 occasional (7.5%) Occasional (29-5%) HP:0000343
26 epicanthus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000286
27 dystonia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001332
28 multiple lipomas 58 31 occasional (7.5%) Occasional (29-5%) HP:0001012
29 ventriculomegaly 58 31 occasional (7.5%) Occasional (29-5%) HP:0002119
30 upslanted palpebral fissure 58 31 occasional (7.5%) Occasional (29-5%) HP:0000582
31 trigonocephaly 58 31 occasional (7.5%) Occasional (29-5%) HP:0000243
32 narrow face 58 31 occasional (7.5%) Occasional (29-5%) HP:0000275
33 cerebral palsy 58 31 occasional (7.5%) Occasional (29-5%) HP:0100021
34 abnormal facial shape 58 31 very rare (1%) Very frequent (99-80%) HP:0001999
35 agenesis of corpus callosum 31 HP:0001274
36 intellectual disability 31 HP:0001249
37 ptosis 31 HP:0000508
38 anteverted nares 31 HP:0000463
39 generalized hypotonia 31 HP:0001290
40 growth delay 58 Very frequent (99-80%)
41 increased serum lactate 31 HP:0002151
42 increased csf lactate 31 HP:0002490
43 cerebral atrophy 31 HP:0002059
44 hyperalaninemia 31 HP:0003348
45 small for gestational age 31 HP:0001518
46 episodic ataxia 31 HP:0002131
47 severe lactic acidosis 31 HP:0004900
48 decreased activity of the pyruvate dehydrogenase complex 31 HP:0002928
49 psychomotor retardation 31 HP:0025356
50 basal ganglia cysts 31 HP:0006799

Symptoms via clinical synopsis from OMIM:

56
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

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

26 (show all 27)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-10 10.51 PEX12
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-104 10.51 PEX12 HIBCH
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-116 10.51 DLAT
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-139 10.51 H2AC18
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-142 10.51 HIBCH
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-145 10.51 PC SUOX HIBCH
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-153 10.51 PC
8 Decreased shRNA abundance (Z-score < -2) GR00366-A-165 10.51 H2AC18
9 Decreased shRNA abundance (Z-score < -2) GR00366-A-171 10.51 PC PEX12 SUOX
10 Decreased shRNA abundance (Z-score < -2) GR00366-A-181 10.51 SUOX
11 Decreased shRNA abundance (Z-score < -2) GR00366-A-187 10.51 PEX12
12 Decreased shRNA abundance (Z-score < -2) GR00366-A-204 10.51 SUOX
13 Decreased shRNA abundance (Z-score < -2) GR00366-A-209 10.51 SUOX
14 Decreased shRNA abundance (Z-score < -2) GR00366-A-216 10.51 PEX12 SUOX DLAT H2AC18 HIBCH
15 Decreased shRNA abundance (Z-score < -2) GR00366-A-27 10.51 DLAT
16 Decreased shRNA abundance (Z-score < -2) GR00366-A-40 10.51 H2AC18
17 Decreased shRNA abundance (Z-score < -2) GR00366-A-53 10.51 PEX12
18 Decreased shRNA abundance (Z-score < -2) GR00366-A-62 10.51 PC
19 Decreased shRNA abundance (Z-score < -2) GR00366-A-68 10.51 HIBCH
20 Decreased shRNA abundance (Z-score < -2) GR00366-A-84 10.51 SUOX
21 Decreased shRNA abundance (Z-score < -2) GR00366-A-89 10.51 SUOX HIBCH
22 Decreased viability GR00221-A-2 10.05 TAOK3
23 Decreased viability GR00221-A-3 10.05 TAOK3
24 Decreased viability GR00240-S-1 10.05 HIBCH
25 Decreased viability GR00381-A-1 10.05 DLAT PDHB
26 Decreased viability GR00402-S-2 10.05 DLAT ECHS1 ETFDH H2AC18 HIBCH LIPT1
27 no effect GR00402-S-1 9.62 DLAT ECHS1 ETFDH H2AC18 HIBCH LIPT1

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:

40
Brain, Testes, Eye, Cortex, Liver, Heart, Skin

Publications for Pyruvate Dehydrogenase E1-Alpha Deficiency

Articles related to Pyruvate Dehydrogenase E1-Alpha Deficiency:

(show top 50) (show all 181)
# Title Authors PMID Year
1
Cerebral palsy and pyruvate dehydrogenase deficiency: identification of two new mutations in the E1alpha gene. 61 56 6
10486093 1999
2
Pyruvate dehydrogenase E1 alpha deficiency in a family: different clinical presentation in two siblings. 61 56 6
9686362 1998
3
An amino acid substitution in the pyruvate dehydrogenase E1 alpha gene, affecting mitochondrial import of the precursor protein. 61 56 6
7573035 1995
4
A mutation in the E1 alpha subunit of pyruvate dehydrogenase associated with variable expression of pyruvate dehydrogenase complex deficiency. 61 56 6
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. 56 6
12379317 2002
6
Biochemical and molecular analysis of an X-linked case of Leigh syndrome associated with thiamin-responsive pyruvate dehydrogenase deficiency. 56 6
9266390 1997
7
Pyruvate dehydrogenase deficiency. Clinical presentation and molecular genetic characterization of five new patients. 56 6
8032855 1994
8
Pyruvate dehydrogenase deficiency in a male caused by a point mutation (F205L) in the E1 alpha subunit. 56 6
8199595 1994
9
Defective gene in lactic acidosis: abnormal pyruvate dehydrogenase E1 alpha-subunit caused by a frame shift. 56 6
2537010 1989
10
A deficiency of both subunits of pyruvate dehydrogenase which is not expressed in fibroblasts. 56 6
3137520 1988
11
Pyruvate dehydrogenase E1 alpha deficiency: males and females differ yet again. 61 6
7887408 1995
12
Characterization of the mutations in three patients with pyruvate dehydrogenase E1 alpha deficiency. 61 6
1909401 1991
13
Fatal lactic acidosis due to deficiency of E1 component of the pyruvate dehydrogenase complex. 61 56
3139934 1988
14
Pyruvate dehydrogenase complex-E2 deficiency causes paroxysmal exercise-induced dyskinesia. 6
29093066 2017
15
Dihydrolipoamide Dehydrogenase Deficiency 6
25032271 2014
16
Stimulation of reactive oxygen species generation by disease-causing mutations of lipoamide dehydrogenase. 6
21558426 2011
17
Cryptic proteolytic activity of dihydrolipoamide dehydrogenase. 6
17404228 2007
18
Novel mutations in dihydrolipoamide dehydrogenase deficiency in two cousins with borderline-normal PDH complex activity. 6
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. 56
16412675 2006
20
Clinical and genetic spectrum of pyruvate dehydrogenase deficiency: dihydrolipoamide acetyltransferase (E2) deficiency. 6
16049940 2005
21
A novel mutation in the dihydrolipoamide dehydrogenase E3 subunit gene (DLD) resulting in an atypical form of alpha-ketoglutarate dehydrogenase deficiency. 6
15712224 2005
22
Mutations in the gene for the E1beta subunit: a novel cause of pyruvate dehydrogenase deficiency. 6
15138885 2004
23
Leigh syndrome due to compound heterozygosity of dihydrolipoamide dehydrogenase gene mutations. Description of the first E3 splice site mutation. 6
12925875 2003
24
Differential effect of DCA treatment on the pyruvate dehydrogenase complex in patients with severe PDHC deficiency. 56
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. 6
14765544 2003
26
Novel mutations in a boy with dihydrolipoamide dehydrogenase deficiency. 6
11687750 2001
27
Lipoamide dehydrogenase deficiency due to a novel mutation in the interface domain. 6
10448086 1999
28
Molecular basis of lipoamide dehydrogenase deficiency in Ashkenazi Jews. 6
9934985 1999
29
Thiamine-responsive lactic acidaemia: role of pyruvate dehydrogenase complex. 56
9727848 1998
30
Arginine 302 mutations in the pyruvate dehydrogenase E1alpha subunit gene: identification of further patients and in vitro demonstration of pathogenicity. 6
9671272 1998
31
Transfection screening for primary defects in the pyruvate dehydrogenase E1alpha subunit gene. 56
9259285 1997
32
Lipoamide dehydrogenase deficiency in Ashkenazi Jews: an insertion mutation in the mitochondrial leader sequence. 6
9298831 1997
33
Identification of two mutations in a compound heterozygous child with dihydrolipoamide dehydrogenase deficiency. 6
8968745 1996
34
Leigh disease with deficiency of lipoamide dehydrogenase: treatment failure with dichloroacetate. 6
8652022 1996
35
Association of cerebral dysgenesis and lactic acidemia with X-linked PDH E1 alpha subunit mutations in females. 6
8771169 1995
36
Pyruvate dehydrogenase deficiency. 56
7853374 1994
37
Cerebral dysgenesis and lactic acidemia: an MRI/MRS phenotype associated with pyruvate dehydrogenase deficiency. 56
7880337 1994
38
Molecular analysis of abnormal pyruvate dehydrogenase in a patient with thiamine-responsive congenital lactic acidemia. 56
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. 6
7692352 1993
40
Molecular genetic characterization of an X-linked form of Leigh's syndrome. 56
8498846 1993
41
Identification of two missense mutations in a dihydrolipoamide dehydrogenase-deficient patient. 6
8506365 1993
42
A four-nucleotide insertion hotspot in the X chromosome located pyruvate dehydrogenase E1 alpha gene (PDHA1). 6
8504309 1993
43
Mutations in the X-linked E1 alpha subunit of pyruvate dehydrogenase leading to deficiency of the pyruvate dehydrogenase complex. 6
8504306 1993
44
Alpha-ketoglutarate dehydrogenase deficiency presenting as congenital lactic acidosis. 6
1640293 1992
45
Mutations and polymorphisms in the pyruvate dehydrogenase E1 alpha gene. 56
1301207 1992
46
X-linked pyruvate dehydrogenase E1 alpha subunit deficiency in heterozygous females: variable manifestation of the same mutation. 56
1293379 1992
47
Mutation of E1 alpha gene in a female patient with pyruvate dehydrogenase deficiency due to rapid degradation of E1 protein. 6
1338114 1992
48
Pyruvate dehydrogenase deficiency due to a 20-bp deletion in exon II of the pyruvate dehydrogenase (PDH) E1 alpha gene. 6
1907799 1991
49
Demonstration of an unstable variant of pyruvate dehydrogenase protein (E1) in cultured fibroblasts from a patient with congenital lactic acidemia. 6
1909778 1991
50
Pyruvate dehydrogenase deficiency due to a mutation of the E1 alpha subunit. 6
1770778 1991

Variations for Pyruvate Dehydrogenase E1-Alpha Deficiency

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

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# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 PDHA1 NM_000284.4(PDHA1):c.506C>T (p.Ala169Val)SNV Pathogenic 214941 rs863224150 X:19371287-19371287 X:19353169-19353169
2 PDHA1 NM_000284.4(PDHA1):c.910C>T (p.Arg304Ter)SNV Pathogenic 214935 rs863224146 X:19377044-19377044 X:19358926-19358926
3 PDHA1 NM_000284.4(PDHA1):c.1132C>T (p.Arg378Cys)SNV Pathogenic 214936 rs863224147 X:19377730-19377730 X:19359612-19359612
4 PDHA1 NM_000284.4(PDHA1):c.1163_1166CAGT[1] (p.Ser390fs)short repeat Pathogenic 10871 rs606231184 X:19377758-19377761 X:19359640-19359643
5 PDHA1 NM_000284.4(PDHA1):c.927_933AGTAAGA[1] (p.Ser312fs)short repeat Pathogenic 10872 rs606231185 X:19377059-19377065 X:19358941-19358947
6 PDHA1 NM_000284.4(PDHA1):c.1133G>A (p.Arg378His)SNV Pathogenic 10873 rs137853250 X:19377731-19377731 X:19359613-19359613
7 PDHA1 NM_000284.4(PDHA1):c.938_940del (p.Lys313del)deletion Pathogenic 10874 rs137853251 X:19377071-19377073 X:19358953-19358955
8 PDHA1 NM_000284.4(PDHA1):c.1159_1160del (p.Lys387fs)deletion Pathogenic 10875 rs606231186 X:19377757-19377758 X:19359639-19359640
9 PDHA1 NM_000284.4(PDHA1):c.1073_1092del (p.Glu358fs)deletion Pathogenic 10876 rs606231187 X:19377668-19377687 X:19359550-19359569
10 PDHA1 NM_000284.4(PDHA1):c.900-3_917dupduplication Pathogenic 10877 rs606231188 X:19377029-19377030 X:19358911-19358912
11 PDHA1 NM_000284.4(PDHA1):c.787C>G (p.Arg263Gly)SNV Pathogenic 10878 rs137853259 X:19373831-19373831 X:19355713-19355713
12 PDHA1 NM_000284.4(PDHA1):c.904C>T (p.Arg302Cys)SNV Pathogenic 10879 rs137853252 X:19377038-19377038 X:19358920-19358920
13 PDHA1 NM_000284.4(PDHA1):c.1142_1145dup (p.Trp383fs)duplication Pathogenic 10880 rs606231189 X:19377737-19377738 X:19359619-19359620
14 PDHA1 NM_000284.4(PDHA1):c.773A>C (p.Asp258Ala)SNV Pathogenic 10881 rs137853253 X:19373817-19373817 X:19355699-19355699
15 PDHA1 NM_000284.4(PDHA1):c.615C>G (p.Phe205Leu)SNV Pathogenic 10882 rs137853254 X:19373478-19373478 X:19355360-19355360
16 PDHA1 NM_000284.4(PDHA1):c.727T>A (p.Tyr243Asn)SNV Pathogenic 10883 rs137853255 X:19373590-19373590 X:19355472-19355472
17 PDHA1 NM_000284.4(PDHA1):c.943G>A (p.Asp315Asn)SNV Pathogenic 10884 rs137853256 X:19377077-19377077 X:19358959-19358959
18 PDHA1 NM_000284.4(PDHA1):c.422G>A (p.Arg141Gln)SNV Pathogenic 202188 rs794729213 X:19371203-19371203 X:19353085-19353085
19 PDHA1 NM_000284.4(PDHA1):c.861_862insT (p.Arg288fs)insertion Pathogenic 10886 rs606231190 X:19375799-19375800 X:19357681-19357682
20 PDHA1 NM_000284.4(PDHA1):c.29G>C (p.Arg10Pro)SNV Pathogenic 10887 rs137853257 X:19362184-19362184 X:19344066-19344066
21 PDHA1 PDHA1, 13-BP INS, EX10insertion Pathogenic 10888
22 PDHA1 NM_000284.4(PDHA1):c.1074_1109dup (p.Pro359_Ser370dup)duplication Pathogenic 10889 rs606231191 X:19377671-19377672 X:19359553-19359554
23 PDHA1 NM_000284.4(PDHA1):c.863G>A (p.Arg288His)SNV Pathogenic 10890 rs137853258 X:19375801-19375801 X:19357683-19357683
24 PDHA1 NM_000284.4(PDHA1):c.*79_*90dupduplication Pathogenic 10891 rs1555935690 X:19377849-19377850 X:19359731-19359732
25 PDHA1 NM_000284.4(PDHA1):c.648A>C (p.Leu216Phe)SNV Pathogenic 10893 rs121917898 X:19373511-19373511 X:19355393-19355393
26 PDHA1 NM_000284.4(PDHA1):c.292-23A>GSNV Pathogenic 374330 rs1057518702 X:19369376-19369376 X:19351258-19351258
27 PDHA1 NM_000284.4(PDHA1):c.482A>G (p.Tyr161Cys)SNV Pathogenic 560929 rs1569190962 X:19371263-19371263 X:19353145-19353145
28 PDHA1 NM_000284.4(PDHA1):c.523G>A (p.Ala175Thr)SNV Pathogenic 561078 rs1569191372 X:19372621-19372621 X:19354503-19354503
29 PDHA1 NM_000284.4(PDHA1):c.1026_1039del (p.Arg343fs)deletion Pathogenic 560930 rs1569194036 X:19377624-19377637 X:19359506-19359519
30 PDHA1 NM_000284.4(PDHA1):c.58-1G>ASNV Pathogenic 567912 rs1569189834 X:19367429-19367429 X:19349311-19349311
31 PDHA1 NM_000284.4(PDHA1):c.930_932AAG[1] (p.Arg311del)short repeat Pathogenic 488571 rs1555935223 X:19377064-19377066 X:19358946-19358948
32 PDHA1 NM_000284.4(PDHA1):c.491A>G (p.Asn164Ser)SNV Pathogenic 488569 rs1555933963 X:19371272-19371272 X:19353154-19353154
33 PDHA1 NM_000284.4(PDHA1):c.225G>T (p.Glu75Asp)SNV Pathogenic 627558 rs1569190079 X:19368162-19368162 X:19350044-19350044
34 PDHA1 NM_000284.4(PDHA1):c.934_992dup (p.Ser331delinsArgValArgValThrLeuLeuCysPheSerArgThrGlyTrpTer)duplication Pathogenic 640193 X:19377067-19377068 X:19358949-19358950
35 PDHA1 NM_000284.4(PDHA1):c.822_826dup (p.Gly276fs)duplication Pathogenic 803732 X:19373864-19373865 X:19355746-19355747
36 PDHA1 NM_000284.4(PDHA1):c.642G>T (p.Trp214Cys)SNV Pathogenic 807461 X:19373505-19373505 X:19355387-19355387
37 PDHA1 NM_000284.4(PDHA1):c.738C>T (p.Gly246=)SNV Pathogenic/Likely pathogenic 432160 rs1555934379 X:19373601-19373601 X:19355483-19355483
38 PDHA1 NM_000284.4(PDHA1):c.214C>T (p.Arg72Cys)SNV Pathogenic/Likely pathogenic 214938 rs863224148 X:19368151-19368151 X:19350033-19350033
39 PDHA1 NM_000284.4(PDHA1):c.455C>T (p.Ser152Leu)SNV Likely pathogenic 488568 rs1555933954 X:19371236-19371236 X:19353118-19353118
40 PDHA1 NM_000284.4(PDHA1):c.461A>G (p.His154Arg)SNV Likely pathogenic 430806 rs1131692230 X:19371242-19371242 X:19353124-19353124
41 PDHX NM_001166158.1(PDHX):c.-197deldeletion Likely pathogenic 590822 rs1158194122 11:34938006-34938006 11:34916459-34916459
42 PDHA1 NM_000284.4(PDHA1):c.300_301dup (p.Cys101fs)duplication Likely pathogenic 590820 rs1569190422 X:19369406-19369407 X:19351288-19351289
43 PDHA1 NM_000284.4(PDHA1):c.789_790AG[1] (p.Glu264fs)short repeat Likely pathogenic 590821 rs1569191879 X:19373832-19373833 X:19355714-19355715
44 PDHA1 NM_000284.4(PDHA1):c.291+1_418+1dupduplication Likely pathogenic 599237 X:19368227-19368228 X:19350109-19350110
45 PDHA1 NM_000284.4(PDHA1):c.749C>T (p.Pro250Leu)SNV Likely pathogenic 637039 X:19373612-19373612 X:19355494-19355494
46 PDHA1 NM_000284.4(PDHA1):c.536T>G (p.Leu179Arg)SNV Likely pathogenic 488570 rs1555934165 X:19372634-19372634 X:19354516-19354516
47 PDHA1 NM_000284.4(PDHA1):c.1050_1133dup (p.Gln351_Arg378dup)duplication Likely pathogenic 495793 rs1555935486 X:19377647-19377648 X:19359529-19359530
48 PDHA1 NM_000284.4(PDHA1):c.692C>G (p.Thr231Arg)SNV Conflicting interpretations of pathogenicity 650357 X:19373555-19373555 X:19355437-19355437
49 PDHX NM_003477.3(PDHX):c.47A>C (p.Tyr16Ser)SNV Conflicting interpretations of pathogenicity 304461 rs118136428 11:34938249-34938249 11:34916702-34916702
50 PDHX NM_003477.3(PDHX):c.474G>A (p.Glu158=)SNV Conflicting interpretations of pathogenicity 304464 rs148723565 11:34979062-34979062 11:34957515-34957515

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

73 (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:

36
# 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 14)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.91 SUOX SLC2A1 SLC19A3 PDHX PDHB PDHA1
2
Show member pathways
12.38 SLC2A1 PDHX PDHB PDHA1 PC DLAT
3 12.31 SLC2A1 PDHA1 LONP1 DLAT
4
Show member pathways
11.85 PDHX PDHB PDHA1 DLAT
5
Show member pathways
11.76 PDHB PDHA1 PC HIBCH ECHS1 DLAT
6 11.72 SLC2A1 PDHB PDHA1
7
Show member pathways
11.72 PDHB PDHA1 PC DLAT
8 11.7 SLC2A1 PDHB PDHA1
9 11.63 PDHX PDHA1 PC HIBCH
10 11.47 SLC2A1 PDHB PDHA1
11
Show member pathways
11.38 PDHX PDHB PDHA1 DLAT
12
Show member pathways
11.08 PDHB PDHA1 PC DLAT
13 10.88 PC ECHS1
14
Show member pathways
10.57 PDHX PDHB PDHA1 LIPT1 DLAT

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 9.77 SUOX POLG PDHX PDHB PDHA1 PC
2 pyruvate dehydrogenase complex GO:0045254 9.46 PDHX PDHB PDHA1 DLAT
3 mitochondrial matrix GO:0005759 9.36 SUOX PDHX PDHB PDHA1 PC LONP1

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 9.5 PDHB PDHA1 DLAT
2 tricarboxylic acid cycle GO:0006099 9.43 PDHB PDHA1 DLAT
3 mitochondrial acetyl-CoA biosynthetic process from pyruvate GO:0061732 9.33 PDHX PDHB PDHA1
4 acetyl-CoA biosynthetic process from pyruvate GO:0006086 9.13 PDHB PDHA1 DLAT
5 pyruvate metabolic process GO:0006090 9.02 PDHX PDHB PDHA1 PC DLAT

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 8.96 PDHB PDHA1
2 pyruvate dehydrogenase (NAD+) activity GO:0034604 8.92 PDHX PDHB PDHA1 DLAT

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 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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