PDHAD
MCID: PYR022
MIFTS: 63

Pyruvate Dehydrogenase E1-Alpha Deficiency (PDHAD)

Categories: Genetic diseases, Metabolic diseases, Muscle 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 58 72 36 29 13 6 39
Pyruvate Dehydrogenase Complex Deficiency 57 20 43 58 36 29 6
Pyruvate Decarboxylase Deficiency 57 12 20 58 72 15 17
Pyruvate Dehydrogenase Deficiency 12 73 20 43 58 72
Pdh Deficiency 57 20 43 72
Pyruvate Dehydrogenase Complex Deficiency Disease 12 44 70
Pdhad 57 58 72
Ataxia with Lactic Acidosis I 57 72
Pdhc 20 58
Pdh 20 58
Ataxia, Intermittent, with Pyruvate Dehydrogenase, or Decarboxylase, Deficiency 20
Ataxia Intermittent with Pyruvate Dehydrogenase or Decarboxylase Deficiency 72
Pyruvate Dehydrogenase Complex E1 Component Subunit Alpha Deficiency 58
Ataxia, Intermittent, with Pyruvate Dehydrogenase Deficiency 57
Intermittent Ataxia with Pyruvate Dehydrogenase Deficiency 43
Ataxia, Intermittent, with Abnormal Pyruvate Metabolism 57
Ataxia Intermittent with Abnormal Pyruvate Metabolism 72
Pyruvate Dehydrogenase E1 Alpha Deficiency 70
Deficiency of Pyruvic Dehydrogenase 12
Ataxia with Lactic Acidosis 1 20
Ataxia with Lactic Acidosis 43
Pdhc Deficiency 43
Pdc Deficiency 20

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®:

57 (Updated 20-May-2021)
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
patients may have no structural abnormalities in the central nervous system
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


Summaries for Pyruvate Dehydrogenase E1-Alpha Deficiency

GARD : 20 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 e2 deficiency and alpha-ketoglutarate dehydrogenase 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 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, eye and cortex, and related phenotypes are feeding difficulties in infancy and increased serum lactate

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.

MedlinePlus Genetics : 43 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) (Updated 20-May-2021)

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 : 72 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 : 73 Pyruvate dehydrogenase deficiency (also known as pyruvate dehydrogenase complex deficiency or PDCD) is a... 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 128)
# Related Disease Score Top Affiliating Genes
1 pyruvate dehydrogenase e2 deficiency 32.7 PIH1D2 DLAT
2 alpha-ketoglutarate dehydrogenase deficiency 32.3 PDHA1 DLD
3 pyruvate dehydrogenase e3-binding protein deficiency 30.8 PDHX PDHA1 DLD
4 leigh syndrome 30.4 SUOX SLC19A3 PDHX PDHB PDHA1 LIPT1
5 primary biliary cholangitis 30.4 PDHX H2AC18 DLD DLAT
6 lactic acidosis 30.2 SLC19A3 PDHX PDHB PDHA1 PC NFU1
7 dystonia 30.1 SUOX SLC2A1 SLC19A3 PDHA1 LIPT1 HIBCH
8 pyruvate carboxylase deficiency 11.7
9 mitochondrial complex iv deficiency, nuclear type 5 11.2
10 hypotonia 10.4
11 encephalopathy 10.3
12 pyruvate dehydrogenase e1-beta deficiency 10.3
13 multiple mitochondrial dysfunctions syndrome 10.3 NFU1 LIAS IBA57
14 ataxia and polyneuropathy, adult-onset 10.3
15 west syndrome 10.3
16 inherited metabolic disorder 10.3
17 nuclear gene-encoded leigh syndrome spectrum 10.3
18 biotin deficiency 10.3 SLC19A3 PC H2AC18
19 multiple mitochondrial dysfunctions syndrome 4 10.3 NFU1 LIAS IBA57
20 leigh syndrome with leukodystrophy 10.3 SLC19A3 PDHA1 LIPT1 ECHS1
21 biotinidase deficiency 10.3 SUOX PC HIBCH H2AC18
22 multiple mitochondrial dysfunctions syndrome 2 with hyperglycinemia 10.2 NFU1 LIAS IBA57
23 neuropathy 10.2
24 multiple mitochondrial dysfunctions syndrome 3 10.2 NFU1 LIAS IBA57
25 propionic acidemia 10.2 PC HIBCH ECHS1
26 marshall-smith syndrome 10.2 PDHB PDHA1
27 dihydrolipoamide dehydrogenase deficiency 10.2
28 kearns-sayre syndrome 10.2
29 mitochondrial disorders 10.2
30 lipoic acid biosynthesis defects 10.2 NFU1 LIPT2 LIPT1 LIAS DLD
31 metabolic acidosis 10.2
32 microcephaly 10.2
33 hydrocephalus 10.2
34 periventricular leukomalacia 10.2
35 overgrowth syndrome 10.2
36 multiple mitochondrial dysfunctions syndrome 1 10.2 NFU1 LIPT2 LIPT1 LIAS IBA57
37 maple syrup urine disease 10.1 SUOX LIPT2 DLD
38 hyper-beta-alaninemia 10.1
39 alacrima, achalasia, and mental retardation syndrome 10.1
40 alcohol-related neurodevelopmental disorder 10.1
41 optic nerve disease 10.1
42 movement disease 10.1
43 peripheral nervous system disease 10.1
44 necrotizing fasciitis 10.1 LIAS H2AC18
45 progressive familial heart block, type ia 10.0
46 macular degeneration, age-related, 2 10.0
47 mitochondrial complex iv deficiency, nuclear type 1 10.0
48 hydrocephalus due to congenital stenosis of aqueduct of sylvius 10.0
49 3-methylglutaconic aciduria, type i 10.0
50 cyclic vomiting syndrome 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:

58 31 (show top 50) (show all 97)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 feeding difficulties in infancy 58 31 hallmark (90%) Very frequent (99-80%) HP:0008872
2 increased serum lactate 58 31 hallmark (90%) Very frequent (99-80%) HP:0002151
3 lethargy 58 31 hallmark (90%) Very frequent (99-80%) HP:0001254
4 increased csf lactate 58 31 hallmark (90%) Very frequent (99-80%) HP:0002490
5 small for gestational age 58 31 hallmark (90%) Very frequent (99-80%) HP:0001518
6 abnormal csf pyruvate family amino acid concentration 58 31 hallmark (90%) Very frequent (99-80%) HP:0500231
7 hypotonia 31 hallmark (90%) HP:0001252
8 spasticity 58 31 frequent (33%) Frequent (79-30%) HP:0001257
9 abnormal pyramidal sign 58 31 frequent (33%) Frequent (79-30%) HP:0007256
10 abnormality of eye movement 58 31 frequent (33%) Frequent (79-30%) HP:0000496
11 ataxia 58 31 frequent (33%) Frequent (79-30%),Occasional (29-5%) HP:0001251
12 dysarthria 58 31 frequent (33%) Frequent (79-30%) HP:0001260
13 gait disturbance 58 31 frequent (33%) Frequent (79-30%) HP:0001288
14 tremor 58 31 frequent (33%) Frequent (79-30%) HP:0001337
15 global developmental delay 58 31 frequent (33%) Frequent (79-30%) HP:0001263
16 abnormal facial shape 58 31 very rare (1%) Very frequent (99-80%),Frequent (79-30%) HP:0001999
17 microcephaly 58 31 frequent (33%) Frequent (79-30%),Occasional (29-5%) HP:0000252
18 intrauterine growth retardation 58 31 frequent (33%) Frequent (79-30%),Frequent (79-30%) HP:0001511
19 aplasia/hypoplasia of the corpus callosum 58 31 frequent (33%) Frequent (79-30%) HP:0007370
20 increased serum pyruvate 58 31 frequent (33%) Frequent (79-30%) HP:0003542
21 choreoathetosis 58 31 frequent (33%) Frequent (79-30%) HP:0001266
22 tachypnea 58 31 frequent (33%) Frequent (79-30%) HP:0002789
23 osteolytic defects of the middle phalanx of the 4th toe 58 31 frequent (33%) Frequent (79-30%) HP:0100453
24 intellectual disability, profound 58 31 frequent (33%) Frequent (79-30%) HP:0002187
25 cerebral atrophy 58 31 frequent (33%) Frequent (79-30%) HP:0002059
26 dilation of lateral ventricles 58 31 frequent (33%) Frequent (79-30%) HP:0006956
27 eeg with focal spikes 58 31 frequent (33%) Frequent (79-30%) HP:0011193
28 low apgar score 58 31 frequent (33%) Frequent (79-30%) HP:0030917
29 eeg with focal sharp waves 58 31 frequent (33%) Frequent (79-30%) HP:0011196
30 eeg with generalized sharp slow waves 58 31 frequent (33%) Frequent (79-30%) HP:0011199
31 abnormality of medullary pyramid morphology 58 31 frequent (33%) Frequent (79-30%) HP:0025361
32 congenital lactic acidosis 58 31 frequent (33%) Frequent (79-30%) HP:0004902
33 seizure 31 frequent (33%) HP:0001250
34 bilateral tonic-clonic seizure 31 frequent (33%) HP:0002069
35 frontal bossing 58 31 occasional (7.5%) Occasional (29-5%) HP:0002007
36 high palate 58 31 occasional (7.5%) Occasional (29-5%) HP:0000218
37 hypertelorism 58 31 occasional (7.5%) Occasional (29-5%) HP:0000316
38 wide nasal bridge 58 31 occasional (7.5%) Occasional (29-5%) HP:0000431
39 blindness 58 31 occasional (7.5%) Occasional (29-5%) HP:0000618
40 flexion contracture 58 31 occasional (7.5%) Occasional (29-5%) HP:0001371
41 gastroesophageal reflux 58 31 occasional (7.5%) Occasional (29-5%) HP:0002020
42 epicanthus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000286
43 pectus excavatum 58 31 occasional (7.5%) Occasional (29-5%) HP:0000767
44 multiple lipomas 58 31 occasional (7.5%) Occasional (29-5%) HP:0001012
45 neonatal respiratory distress 58 31 occasional (7.5%) Occasional (29-5%) HP:0002643
46 dyspnea 58 31 occasional (7.5%) Occasional (29-5%) HP:0002094
47 narrow face 58 31 occasional (7.5%) Occasional (29-5%) HP:0000275
48 upslanted palpebral fissure 58 31 occasional (7.5%) Occasional (29-5%) HP:0000582
49 talipes 58 31 occasional (7.5%) Occasional (29-5%) HP:0001883
50 long philtrum 58 31 occasional (7.5%) Occasional (29-5%) HP:0000343

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Neurologic Central Nervous System:
seizures
dysmetria
dystonia
lethargy
choreoathetosis
more
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

Head And Neck Face:
frontal bossing
long philtrum

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 (Updated 20-May-2021)

UMLS symptoms related to Pyruvate Dehydrogenase E1-Alpha Deficiency:


seizures; lethargy; nasal flaring

MGI Mouse Phenotypes related to Pyruvate Dehydrogenase E1-Alpha Deficiency:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 embryo MP:0005380 9.56 DLD HIBCH LIAS LIPT1 LONP1 PDHA1
2 mortality/aging MP:0010768 9.44 DLAT DLD ECHS1 HIBCH LIAS 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

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 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
4 Long-term Treatment With the Ketogenic Diet in Epilepsy and Epilepsy-related Rare Diseases Enrolling by invitation NCT04646850

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, Eye, Cortex, Heart, Testis, Skin

Publications for Pyruvate Dehydrogenase E1-Alpha Deficiency

Articles related to Pyruvate Dehydrogenase E1-Alpha Deficiency:

(show top 50) (show all 225)
# Title Authors PMID Year
1
Cerebral palsy and pyruvate dehydrogenase deficiency: identification of two new mutations in the E1alpha gene. 57 6 61
10486093 1999
2
Pyruvate dehydrogenase E1 alpha deficiency in a family: different clinical presentation in two siblings. 57 6 61
9686362 1998
3
An amino acid substitution in the pyruvate dehydrogenase E1 alpha gene, affecting mitochondrial import of the precursor protein. 61 57 6
7573035 1995
4
A mutation in the E1 alpha subunit of pyruvate dehydrogenase associated with variable expression of pyruvate dehydrogenase complex deficiency. 61 57 6
1508605 1992
5
Differential phenotypic expression of a novel PDHA1 mutation in a female monozygotic twin pair. 6 57
31673819 2019
6
Phenotypic and Neuropathological Characterization of Fetal Pyruvate Dehydrogenase Deficiency. 6 57
26865159 2016
7
Thiamine-responsive pyruvate dehydrogenase deficiency in two patients caused by a point mutation (F205L and L216F) within the thiamine pyrophosphate binding region. 57 6
12379317 2002
8
Biochemical and molecular analysis of an X-linked case of Leigh syndrome associated with thiamin-responsive pyruvate dehydrogenase deficiency. 6 57
9266390 1997
9
Pyruvate dehydrogenase deficiency. Clinical presentation and molecular genetic characterization of five new patients. 57 6
8032855 1994
10
Pyruvate dehydrogenase deficiency in a male caused by a point mutation (F205L) in the E1 alpha subunit. 57 6
8199595 1994
11
Mutations and polymorphisms in the pyruvate dehydrogenase E1 alpha gene. 6 57
1301207 1992
12
X-linked pyruvate dehydrogenase E1 alpha subunit deficiency in heterozygous females: variable manifestation of the same mutation. 6 57
1293379 1992
13
Pyruvate dehydrogenase deficiency caused by deletion of a 7-bp repeat sequence in the E1 alpha gene. 6 57
2378353 1990
14
Defective gene in lactic acidosis: abnormal pyruvate dehydrogenase E1 alpha-subunit caused by a frame shift. 57 6
2537010 1989
15
A deficiency of both subunits of pyruvate dehydrogenase which is not expressed in fibroblasts. 6 57
3137520 1988
16
Enzymatic testing sensitivity, variability and practical diagnostic algorithm for pyruvate dehydrogenase complex (PDC) deficiency. 20 6
28918066 2017
17
Difficulties in recognition of pyruvate dehydrogenase complex deficiency on the basis of clinical and biochemical features. The role of next-generation sequencing. 61 6
27144126 2016
18
Molecular characterization of 82 patients with pyruvate dehydrogenase complex deficiency. Structural implications of novel amino acid substitutions in E1 protein. 6 61
21914562 2011
19
Mutational study in the PDHA1 gene of 40 patients suspected of pyruvate dehydrogenase complex deficiency. 6 61
20002461 2010
20
Pyruvate dehydrogenase complex deficiency: four neurological phenotypes with differing pathogenesis. 6 61
20002125 2010
21
A Korean female patient with thiamine-responsive pyruvate dehydrogenase complex deficiency due to a novel point mutation (Y161C)in the PDHA1 gene. 6 61
17043409 2006
22
Caveats when considering ketogenic diets for the treatment of pyruvate dehydrogenase complex deficiency. 61 6
11241048 2001
23
Analysis of exonic mutations leading to exon skipping in patients with pyruvate dehydrogenase E1 alpha deficiency. 6 61
11102541 2000
24
Mutations in the X-linked pyruvate dehydrogenase (E1) alpha subunit gene (PDHA1) in patients with a pyruvate dehydrogenase complex deficiency. 61 6
10679936 2000
25
Pyruvate dehydrogenase E1 alpha deficiency: males and females differ yet again. 61 6
7887408 1995
26
Characterization of the mutations in three patients with pyruvate dehydrogenase E1 alpha deficiency. 61 6
1909401 1991
27
Fatal lactic acidosis due to deficiency of E1 component of the pyruvate dehydrogenase complex. 61 57
3139934 1988
28
Pyruvate dehydrogenase complex-E2 deficiency causes paroxysmal exercise-induced dyskinesia. 6
29093066 2017
29
The clinical and genetic characteristics in children with mitochondrial disease in China. 6
28639102 2017
30
Structural alterations induced by ten disease-causing mutations of human dihydrolipoamide dehydrogenase analyzed by hydrogen/deuterium-exchange mass spectrometry: Implications for the structural basis of E3 deficiency. 6
27544700 2016
31
Clinical application of whole-exome sequencing across clinical indications. 6
26633542 2016
32
New perspective in diagnostics of mitochondrial disorders: two years' experience with whole-exome sequencing at a national paediatric centre. 6
27290639 2016
33
Severe encephalopathy associated to pyruvate dehydrogenase mutations and unbalanced coenzyme Q10 content. 6
26014431 2016
34
Whole-exome sequencing in undiagnosed genetic diseases: interpreting 119 trios. 6
25590979 2015
35
Thiamine-Responsive and Non-responsive Patients with PDHC-E1 Deficiency: A Retrospective Assessment. 6
24718837 2015
36
Riboflavin responsive mitochondrial myopathy is a new phenotype of dihydrolipoamide dehydrogenase deficiency. The chaperon-like effect of vitamin B2. 6
25251739 2014
37
Phenylbutyrate increases pyruvate dehydrogenase complex activity in cells harboring a variety of defects. 6
25356417 2014
38
Elevated plasma citrulline: look for dihydrolipoamide dehydrogenase deficiency. 6
23995961 2014
39
Mutation Spectrum and Birth Prevalence of Inborn Errors of Metabolism among Emiratis: A study from Tawam Hospital Metabolic Center, United Arab Emirates. 6
24516753 2014
40
Newborn screening for dihydrolipoamide dehydrogenase deficiency: Citrulline as a useful analyte. 6
27896107 2014
41
Dihydrolipoamide dehydrogenase deficiency: a still overlooked cause of recurrent acute liver failure and Reye-like syndrome. 6
23478190 2013
42
Leigh syndrome in a girl with a novel DLD mutation causing E3 deficiency. 6
23290025 2013
43
Spectrum of neurological and survival outcomes in pyruvate dehydrogenase complex (PDC) deficiency: lack of correlation with genotype. 6
23021068 2012
44
A 1.1 million base pair X-chromosomal deletion covering the PDHA1 and CDKL5 genes in a female patient with West syndrome and pyruvate oxidation deficiency. 6
22473288 2012
45
Mutations in the dimer interface of dihydrolipoamide dehydrogenase promote site-specific oxidative damages in yeast and human cells. 6
21930696 2011
46
Increased superoxide accumulation in pyruvate dehydrogenase complex deficient fibroblasts. 6
21846590 2011
47
Stimulation of reactive oxygen species generation by disease-causing mutations of lipoamide dehydrogenase. 6
21558426 2011
48
Deletion at chromosomal band Xp22.12-Xp22.13 involving PDHA1 in a patient with congenital lactic acidosis. 6
20591708 2010
49
PDH E1β deficiency with novel mutations in two patients with Leigh syndrome. 6
19924563 2009
50
Neonatal pyruvate dehydrogenase deficiency due to a R302H mutation in the PDHA1 gene: MRI findings. 6
18197404 2008

Variations for Pyruvate Dehydrogenase E1-Alpha Deficiency

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

6 (show top 50) (show all 529)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 DLD NM_000108.5(DLD):c.214A>G (p.Lys72Glu) SNV Pathogenic 11964 rs121964987 GRCh37: 7:107542785-107542785
GRCh38: 7:107902340-107902340
2 DLD NM_000108.5(DLD):c.1463C>T (p.Pro488Leu) SNV Pathogenic 11965 rs121964988 GRCh37: 7:107559543-107559543
GRCh38: 7:107919098-107919098
3 DLD NM_000108.5(DLD):c.1483A>G (p.Arg495Gly) SNV Pathogenic 11968 rs121964989 GRCh37: 7:107559657-107559657
GRCh38: 7:107919212-107919212
4 DLD NM_000108.5(DLD):c.1178T>C (p.Ile393Thr) SNV Pathogenic 11969 rs121964991 GRCh37: 7:107557849-107557849
GRCh38: 7:107917404-107917404
5 DLD NM_000108.5(DLD):c.1081A>G (p.Met361Val) SNV Pathogenic 11972 rs121964993 GRCh37: 7:107557752-107557752
GRCh38: 7:107917307-107917307
6 DLD NM_000108.5(DLD):c.1444A>G (p.Arg482Gly) SNV Pathogenic 40187 rs397514650 GRCh37: 7:107559524-107559524
GRCh38: 7:107919079-107919079
7 DLD NM_000108.5(DLD):c.140T>C (p.Ile47Thr) SNV Pathogenic 40188 rs397514651 GRCh37: 7:107542204-107542204
GRCh38: 7:107901759-107901759
8 DLD NM_000108.5(DLD):c.12G>A (p.Trp4Ter) SNV Pathogenic 572549 rs1562908173 GRCh37: 7:107531707-107531707
GRCh38: 7:107891262-107891262
9 DLD NC_000007.14:g.(?_107901728)_(107906378_?)del Deletion Pathogenic 831013 GRCh37: 7:107542173-107546823
GRCh38:
10 DLD NM_000108.5(DLD):c.946C>T (p.Arg316Ter) SNV Pathogenic 854640 GRCh37: 7:107557309-107557309
GRCh38: 7:107916864-107916864
11 DLD NM_000108.5(DLD):c.1340_1343CAGA[1] (p.Asp448fs) Microsatellite Pathogenic 856335 GRCh37: 7:107558470-107558473
GRCh38: 7:107918025-107918028
12 DLD NM_000108.5(DLD):c.821dup (p.Leu274fs) Duplication Pathogenic 960146 GRCh37: 7:107556085-107556086
GRCh38: 7:107915640-107915641
13 DLD NM_000108.5(DLD):c.308_310delinsT (p.Gly103fs) Indel Pathogenic 969750 GRCh37: 7:107543963-107543965
GRCh38: 7:107903518-107903520
14 DLAT DLAT, 3-BP DEL, 361GAA Deletion Pathogenic 2109 GRCh37:
GRCh38:
15 PIH1D2 , DLAT NM_001931.5(DLAT):c.1728C>A (p.Phe576Leu) SNV Pathogenic 2110 rs119103240 GRCh37: 11:111931812-111931812
GRCh38: 11:112061088-112061088
16 PDHA1 NM_000284.4(PDHA1):c.1163_1166CAGT[1] (p.Ser390fs) Microsatellite Pathogenic 10871 rs606231184 GRCh37: X:19377758-19377761
GRCh38: X:19359640-19359643
17 PDHA1 NM_000284.4(PDHA1):c.1133G>A (p.Arg378His) SNV Pathogenic 10873 rs137853250 GRCh37: X:19377731-19377731
GRCh38: X:19359613-19359613
18 PDHA1 NM_000284.4(PDHA1):c.938_940del (p.Lys313del) Deletion Pathogenic 10874 rs137853251 GRCh37: X:19377071-19377073
GRCh38: X:19358953-19358955
19 PDHA1 NM_000284.4(PDHA1):c.1159_1160del (p.Lys387fs) Deletion Pathogenic 10875 rs606231186 GRCh37: X:19377757-19377758
GRCh38: X:19359639-19359640
20 PDHA1 NM_000284.4(PDHA1):c.1073_1092del (p.Glu358fs) Deletion Pathogenic 10876 rs606231187 GRCh37: X:19377668-19377687
GRCh38: X:19359550-19359569
21 PDHA1 NM_000284.4(PDHA1):c.900-3_917dup Duplication Pathogenic 10877 rs606231188 GRCh37: X:19377029-19377030
GRCh38: X:19358911-19358912
22 PDHA1 NM_000284.4(PDHA1):c.904C>T (p.Arg302Cys) SNV Pathogenic 10879 rs137853252 GRCh37: X:19377038-19377038
GRCh38: X:19358920-19358920
23 PDHA1 NM_000284.4(PDHA1):c.1142_1145dup (p.Trp383fs) Duplication Pathogenic 10880 rs606231189 GRCh37: X:19377737-19377738
GRCh38: X:19359619-19359620
24 PDHA1 NM_000284.4(PDHA1):c.773A>C (p.Asp258Ala) SNV Pathogenic 10881 rs137853253 GRCh37: X:19373817-19373817
GRCh38: X:19355699-19355699
25 PDHA1 NM_000284.4(PDHA1):c.727T>A (p.Tyr243Asn) SNV Pathogenic 10883 rs137853255 GRCh37: X:19373590-19373590
GRCh38: X:19355472-19355472
26 PDHA1 NM_000284.4(PDHA1):c.943G>A (p.Asp315Asn) SNV Pathogenic 10884 rs137853256 GRCh37: X:19377077-19377077
GRCh38: X:19358959-19358959
27 PDHA1 NM_000284.4(PDHA1):c.861_862insT (p.Arg288fs) Insertion Pathogenic 10886 rs606231190 GRCh37: X:19375799-19375800
GRCh38: X:19357681-19357682
28 PDHA1 NM_000284.4(PDHA1):c.29G>C (p.Arg10Pro) SNV Pathogenic 10887 rs137853257 GRCh37: X:19362184-19362184
GRCh38: X:19344066-19344066
29 PDHA1 PDHA1, 13-BP INS, EX10 Insertion Pathogenic 10888 GRCh37:
GRCh38:
30 PDHA1 NM_000284.4(PDHA1):c.1074_1109dup (p.Pro359_Ser370dup) Duplication Pathogenic 10889 rs606231191 GRCh37: X:19377671-19377672
GRCh38: X:19359553-19359554
31 PDHA1 NM_000284.4(PDHA1):c.863G>A (p.Arg288His) SNV Pathogenic 10890 rs137853258 GRCh37: X:19375801-19375801
GRCh38: X:19357683-19357683
32 PDHA1 NM_000284.4(PDHA1):c.*79_*90dup Duplication Pathogenic 10891 rs1555935690 GRCh37: X:19377849-19377850
GRCh38: X:19359731-19359732
33 PDHA1 NM_000284.4(PDHA1):c.648A>C (p.Leu216Phe) SNV Pathogenic 10893 rs121917898 GRCh37: X:19373511-19373511
GRCh38: X:19355393-19355393
34 PDHA1 NM_000284.4(PDHA1):c.422G>A (p.Arg141Gln) SNV Pathogenic 202188 rs794729213 GRCh37: X:19371203-19371203
GRCh38: X:19353085-19353085
35 DLD NM_000108.5(DLD):c.105del (p.Thr34_Tyr35insTer) Deletion Pathogenic 553084 rs1554396895 GRCh37: 7:107533710-107533710
GRCh38: 7:107893265-107893265
36 PDHB NM_000925.4(PDHB):c.1030C>T (p.Pro344Ser) SNV Pathogenic 13189 rs28933391 GRCh37: 3:58413811-58413811
GRCh38: 3:58428084-58428084
37 PDHB NM_000925.4(PDHB):c.395A>G (p.Tyr132Cys) SNV Pathogenic 13188 rs28935769 GRCh37: 3:58416578-58416578
GRCh38: 3:58430851-58430851
38 PDHA1 NM_000284.4(PDHA1):c.292-23A>G SNV Pathogenic 374330 rs1057518702 GRCh37: X:19369376-19369376
GRCh38: X:19351258-19351258
39 PDHA1 NM_000284.4(PDHA1):c.1132C>T (p.Arg378Cys) SNV Pathogenic 214936 rs863224147 GRCh37: X:19377730-19377730
GRCh38: X:19359612-19359612
40 PDHA1 NM_000284.4(PDHA1):c.491A>G (p.Asn164Ser) SNV Pathogenic 488569 rs1555933963 GRCh37: X:19371272-19371272
GRCh38: X:19353154-19353154
41 PDHA1 NM_000284.4(PDHA1):c.930_932AAG[1] (p.Arg311del) Microsatellite Pathogenic 488571 rs1555935223 GRCh37: X:19377064-19377066
GRCh38: X:19358946-19358948
42 PDHA1 NM_000284.4(PDHA1):c.506C>T (p.Ala169Val) SNV Pathogenic 214941 rs863224150 GRCh37: X:19371287-19371287
GRCh38: X:19353169-19353169
43 PDHA1 NM_000284.4(PDHA1):c.523G>A (p.Ala175Thr) SNV Pathogenic 561078 rs1569191372 GRCh37: X:19372621-19372621
GRCh38: X:19354503-19354503
44 PDHA1 NM_000284.4(PDHA1):c.58-1G>A SNV Pathogenic 567912 rs1569189834 GRCh37: X:19367429-19367429
GRCh38: X:19349311-19349311
45 PDHA1 NM_000284.4(PDHA1):c.214C>T (p.Arg72Cys) SNV Pathogenic 214938 rs863224148 GRCh37: X:19368151-19368151
GRCh38: X:19350033-19350033
46 PDHA1 NM_000284.4(PDHA1):c.910C>T (p.Arg304Ter) SNV Pathogenic 214935 GRCh37: X:19377044-19377044
GRCh38: X:19358926-19358926
47 DLAT NM_001931.5(DLAT):c.470T>G (p.Val157Gly) SNV Pathogenic 208790 rs797044957 GRCh37: 11:111899327-111899327
GRCh38: 11:112028603-112028603
48 PDHA1 NM_000284.4(PDHA1):c.225G>T (p.Glu75Asp) SNV Pathogenic 627558 rs1569190079 GRCh37: X:19368162-19368162
GRCh38: X:19350044-19350044
49 PDHA1 NM_000284.4(PDHA1):c.934_992dup (p.Ser331delinsArgValArgValThrLeuLeuCysPheSerArgThrGlyTrpTer) Duplication Pathogenic 640193 rs1602231539 GRCh37: X:19377067-19377068
GRCh38: X:19358949-19358950
50 PDHA1 NM_000284.4(PDHA1):c.482A>G (p.Tyr161Cys) SNV Pathogenic 560929 rs1569190962 GRCh37: X:19371263-19371263
GRCh38: X:19353145-19353145

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

72 (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 19)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.95 SUOX SLC2A1 SLC19A3 PDHX PDHB PDHA1
2
Show member pathways
13.65 SUOX PDHX PDHB PDHA1 LIPT2 LIPT1
3
Show member pathways
12.55 SLC2A1 PDHX PDHB PDHA1 PC DLD
4 12.34 SLC2A1 PDHA1 LONP1 DLAT
5
Show member pathways
12.02 LIPT2 LIPT1 LIAS DLD
6
Show member pathways
11.95 PDHX PDHB PDHA1 DLD DLAT
7
Show member pathways
11.83 PDHB PDHA1 PC HIBCH ECHS1 DLD
8
Show member pathways
11.82 HIBCH ECHS1 DLD
9 11.77 SLC2A1 PDHB PDHA1
10 11.74 SLC2A1 PDHB PDHA1
11
Show member pathways
11.73 PDHB PDHA1 PC DLD DLAT
12 11.61 PDHX PDHA1 PC HIBCH DLD
13 11.55 SLC2A1 PDHB PDHA1
14
Show member pathways
11.37 PDHX PDHB PDHA1 DLD DLAT
15 11.18 HIBCH ECHS1 DLD
16
Show member pathways
10.98 SUOX DLD
17 10.92 PC ECHS1
18
Show member pathways
10.77 PDHX PDHB PDHA1 LIPT2 LIPT1 LIAS
19
Show member pathways
10.43 LIPT2 LIPT1 LIAS

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 9.83 SUOX PDHX PDHB PDHA1 PC NFU1
2 pyruvate dehydrogenase complex GO:0045254 9.55 PDHX PDHB PDHA1 DLD DLAT
3 mitochondrial matrix GO:0005759 9.47 SUOX PDHX PDHB PDHA1 PC LONP1
4 mitochondrial pyruvate dehydrogenase complex GO:0005967 9.43 PDHB PDHA1 DLAT

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

# Name GO ID Score Top Affiliating Genes
1 tricarboxylic acid cycle GO:0006099 9.62 PDHB PDHA1 DLD DLAT
2 glucose metabolic process GO:0006006 9.58 PDHB PDHA1 DLAT
3 cellular nitrogen compound metabolic process GO:0034641 9.54 LIPT2 LIPT1 LIAS
4 iron-sulfur cluster assembly GO:0016226 9.46 NFU1 IBA57
5 mitochondrial acetyl-CoA biosynthetic process from pyruvate GO:0061732 9.46 PDHX PDHB PDHA1 DLD
6 branched-chain amino acid catabolic process GO:0009083 9.43 HIBCH DLD
7 protein lipoylation GO:0009249 9.43 LIPT2 LIPT1 LIAS
8 acetyl-CoA biosynthetic process from pyruvate GO:0006086 9.26 PDHB PDHA1 DLD DLAT
9 pyruvate metabolic process GO:0006090 9.1 PDHX PDHB PDHA1 PC DLD DLAT

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

# Name GO ID Score Top Affiliating Genes
1 transferase activity, transferring acyl groups GO:0016746 9.46 PDHX LIPT2 LIPT1 DLAT
2 pyruvate dehydrogenase (NAD+) activity GO:0034604 9.02 PDHX PDHB PDHA1 DLD DLAT
3 pyruvate dehydrogenase (acetyl-transferring) activity GO:0004739 8.96 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
20 GARD
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
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
Content
Loading form....