PDHAD
MCID: PYR022
MIFTS: 56

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 58 60 76 38 30 13 6 41
Pyruvate Dehydrogenase Complex Deficiency 58 54 26 60 38 30 6
Pyruvate Decarboxylase Deficiency 58 12 54 60 76 15 17
Pyruvate Dehydrogenase Deficiency 12 77 54 26 60 76
Pdh Deficiency 58 54 26 76
Pyruvate Dehydrogenase Complex Deficiency Disease 12 45 74
Pdhad 58 60 76
Ataxia with Lactic Acidosis I 58 76
Pdhc 54 60
Ataxia, Intermittent, with Pyruvate Dehydrogenase, or Decarboxylase, Deficiency 54
Ataxia Intermittent with Pyruvate Dehydrogenase or Decarboxylase Deficiency 76
Pyruvate Dehydrogenase Complex E1 Component Subunit Alpha Deficiency 60
Ataxia, Intermittent, with Pyruvate Dehydrogenase Deficiency 58
Intermittent Ataxia with Pyruvate Dehydrogenase Deficiency 26
Ataxia, Intermittent, with Abnormal Pyruvate Metabolism 58
Ataxia Intermittent with Abnormal Pyruvate Metabolism 76
Pyruvate Dehydrogenase E1 Alpha Deficiency 74
Deficiency of Pyruvic Dehydrogenase 12
Ataxia with Lactic Acidosis 1 54
Ataxia with Lactic Acidosis 26
Pdhc Deficiency 26
Pdc Deficiency 54
Pdh 60

Characteristics:

Orphanet epidemiological data:

60
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:

58
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:

33
pyruvate dehydrogenase e1-alpha deficiency:
Onset and clinical course infantile onset
Inheritance x-linked dominant inheritance


Classifications:



Summaries for Pyruvate Dehydrogenase E1-Alpha Deficiency

NIH Rare Diseases : 54 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 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 : 26 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 : 58 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)

UniProtKB/Swiss-Prot : 76 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 : 77 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 all 46)
# Related Disease Score Top Affiliating Genes
1 pyruvate dehydrogenase e3-binding protein deficiency 29.8 PDHA1 PDHX
2 lactic acidosis 29.6 PDHA1 PDHX
3 leigh syndrome 29.5 PDHA1 PDHB PDHX
4 pyruvate carboxylase deficiency 11.8
5 pyruvate dehydrogenase e2 deficiency 11.6
6 pyruvate dehydrogenase e1-beta deficiency 11.4
7 alpha-ketoglutarate dehydrogenase deficiency 11.3
8 leigh syndrome, french canadian type 11.3
9 pyruvate dehydrogenase phosphatase deficiency 11.3
10 hypoxia 10.2
11 neuropathy 10.1
12 west syndrome 10.1
13 encephalopathy 10.1
14 ischemia 10.1
15 optic nerve disease 10.1
16 dystonia 10.1
17 bowenoid papulosis 10.1
18 macular degeneration, age-related, 2 10.0
19 mitochondrial complex iv deficiency 10.0
20 3-methylglutaconic aciduria, type i 10.0
21 cyclic vomiting syndrome 10.0
22 diabetes and deafness, maternally inherited 10.0
23 polyglucosan body myopathy 1 with or without immunodeficiency 10.0
24 early infantile epileptic encephalopathy 10.0
25 epilepsy 10.0
26 biliary cirrhosis, primary, 1 10.0
27 breast cancer 10.0
28 pelger-huet anomaly 10.0
29 disorganization, mouse, homolog of 10.0
30 dihydrolipoamide dehydrogenase deficiency 10.0
31 human immunodeficiency virus type 1 10.0
32 primary biliary cirrhosis 10.0
33 oral squamous cell carcinoma 10.0
34 atypical autism 10.0
35 histoplasmosis 10.0
36 squamous cell carcinoma 10.0
37 primary biliary cholangitis 10.0
38 down syndrome 9.9
39 cerebral palsy 9.9
40 periventricular leukomalacia 9.9
41 myopathy 9.9
42 peripheral nervous system disease 9.9
43 chronic fatigue syndrome 9.9
44 leukomalacia 9.9
45 spinocerebellar degeneration 9.9
46 mitochondrial metabolism disease 9.5 HIBCH PDHA1

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:

60 33 (show top 50) (show all 53)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 muscular hypotonia 60 33 hallmark (90%) Very frequent (99-80%) HP:0001252
2 feeding difficulties in infancy 60 33 hallmark (90%) Very frequent (99-80%) HP:0008872
3 lethargy 60 33 hallmark (90%) Very frequent (99-80%) HP:0001254
4 abnormality of eye movement 60 33 frequent (33%) Frequent (79-30%) HP:0000496
5 seizures 60 33 frequent (33%) Frequent (79-30%) HP:0001250
6 ataxia 60 33 frequent (33%) Frequent (79-30%) HP:0001251
7 spasticity 60 33 frequent (33%) Frequent (79-30%) HP:0001257
8 dysarthria 60 33 frequent (33%) Frequent (79-30%) HP:0001260
9 gait disturbance 60 33 frequent (33%) Frequent (79-30%) HP:0001288
10 tremor 60 33 frequent (33%) Frequent (79-30%) HP:0001337
11 abnormal pyramidal sign 60 33 frequent (33%) Frequent (79-30%) HP:0007256
12 global developmental delay 60 33 frequent (33%) Frequent (79-30%) HP:0001263
13 microcephaly 60 33 frequent (33%) Frequent (79-30%) HP:0000252
14 intrauterine growth retardation 60 33 frequent (33%) Frequent (79-30%) HP:0001511
15 choreoathetosis 60 33 frequent (33%) Frequent (79-30%) HP:0001266
16 aplasia/hypoplasia of the corpus callosum 60 33 frequent (33%) Frequent (79-30%) HP:0007370
17 tachypnea 60 33 frequent (33%) Frequent (79-30%) HP:0002789
18 osteolytic defects of the middle phalanx of the 4th toe 60 33 frequent (33%) Frequent (79-30%) HP:0100453
19 hypertelorism 60 33 occasional (7.5%) Occasional (29-5%) HP:0000316
20 pectus excavatum 60 33 occasional (7.5%) Occasional (29-5%) HP:0000767
21 frontal bossing 60 33 occasional (7.5%) Occasional (29-5%) HP:0002007
22 high palate 60 33 occasional (7.5%) Occasional (29-5%) HP:0000218
23 wide nasal bridge 60 33 occasional (7.5%) Occasional (29-5%) HP:0000431
24 dyspnea 60 33 occasional (7.5%) Occasional (29-5%) HP:0002094
25 long philtrum 60 33 occasional (7.5%) Occasional (29-5%) HP:0000343
26 epicanthus 60 33 occasional (7.5%) Occasional (29-5%) HP:0000286
27 dystonia 60 33 occasional (7.5%) Occasional (29-5%) HP:0001332
28 multiple lipomas 60 33 occasional (7.5%) Occasional (29-5%) HP:0001012
29 ventriculomegaly 60 33 occasional (7.5%) Occasional (29-5%) HP:0002119
30 trigonocephaly 60 33 occasional (7.5%) Occasional (29-5%) HP:0000243
31 narrow face 60 33 occasional (7.5%) Occasional (29-5%) HP:0000275
32 upslanted palpebral fissure 60 33 occasional (7.5%) Occasional (29-5%) HP:0000582
33 cerebral palsy 60 33 occasional (7.5%) Occasional (29-5%) HP:0100021
34 abnormal facial shape 60 33 very rare (1%) Very frequent (99-80%) HP:0001999
35 agenesis of corpus callosum 33 HP:0001274
36 ptosis 33 HP:0000508
37 intellectual disability 33 HP:0001249
38 anteverted nares 33 HP:0000463
39 growth delay 60 Very frequent (99-80%)
40 increased serum lactate 33 HP:0002151
41 generalized hypotonia 33 HP:0001290
42 cerebral atrophy 33 HP:0002059
43 hyperalaninemia 33 HP:0003348
44 small for gestational age 33 HP:0001518
45 episodic ataxia 33 HP:0002131
46 increased csf lactate 33 HP:0002490
47 severe lactic acidosis 33 HP:0004900
48 decreased activity of the pyruvate dehydrogenase complex 33 HP:0002928
49 basal ganglia cysts 33 HP:0006799
50 flared nostrils 33 HP:0000454

Symptoms via clinical synopsis from OMIM:

58
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:

27 (show all 16)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-104 9.62 HIBCH
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-139 9.62 PDHB
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-142 9.62 HIBCH
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-145 9.62 HIBCH PDHB
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-173 9.62 MAP3K15
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-18 9.62 PDHA1
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-180 9.62 HIBCH
8 Decreased shRNA abundance (Z-score < -2) GR00366-A-191 9.62 PDHA1
9 Decreased shRNA abundance (Z-score < -2) GR00366-A-206 9.62 MAP3K15 PDHB
10 Decreased shRNA abundance (Z-score < -2) GR00366-A-216 9.62 HIBCH
11 Decreased shRNA abundance (Z-score < -2) GR00366-A-27 9.62 MAP3K15
12 Decreased shRNA abundance (Z-score < -2) GR00366-A-60 9.62 PDHA1 MAP3K15
13 Decreased shRNA abundance (Z-score < -2) GR00366-A-61 9.62 PDHB
14 Decreased shRNA abundance (Z-score < -2) GR00366-A-68 9.62 HIBCH PDHA1
15 Decreased shRNA abundance (Z-score < -2) GR00366-A-89 9.62 HIBCH
16 Decreased shRNA abundance (Z-score < -2) GR00366-A-95 9.62 MAP3K15

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,Phase 1,Phase 2
3 4-phenylbutyric acid Phase 1, Phase 2
4 Pharmaceutical Solutions Phase 1

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Trial of Dichloroacetate in Pyruvate Dehydrogenase Complex Deficiency: Recruiting NCT02616484 Phase 3 Dichloroacetate (DCA)
2 Use 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 Completed NCT02690285 Phase 1 Dichloroacetate (DCA)
4 Natural History and Advanced Genetic Study of Pyruvate Dehydrogenase Complex Deficiencies Recruiting NCT03056794

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 30 PDHA1
2 Pyruvate Dehydrogenase Complex Deficiency 30

Anatomical Context for Pyruvate Dehydrogenase E1-Alpha Deficiency

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

42
Brain, Testes, Eye, Cortex, Skin, Testis

Publications for Pyruvate Dehydrogenase E1-Alpha Deficiency

Articles related to Pyruvate Dehydrogenase E1-Alpha Deficiency:

(show top 50) (show all 81)
# Title Authors Year
1
Hypothermic reaction after infection in an infant with pyruvate dehydrogenase complex deficiency. ( 31064704 )
2019
2
LIPT1 deficiency presenting as early infantile epileptic encephalopathy, Leigh disease, and secondary pyruvate dehydrogenase complex deficiency. ( 29681092 )
2018
3
Efficacy of ketogenic diet for pyruvate dehydrogenase complex deficiency. ( 30407699 )
2018
4
Pyruvate dehydrogenase complex deficiency is linked to regulatory loop disorder in the αV138M variant of human pyruvate dehydrogenase. ( 29970614 )
2018
5
Ketogenic diet in pyruvate dehydrogenase complex deficiency: short- and long-term outcomes. ( 28101805 )
2017
6
Thiamine Responsive Pyruvate Dehydrogenase Complex Deficiency: A Potentially Treatable Cause of Leigh's Disease. ( 29204204 )
2017
7
Prenatal presentation of pyruvate dehydrogenase complex deficiency. ( 27026023 )
2016
8
Difficulties in recognition of pyruvate dehydrogenase complex deficiency on the basis of clinical and biochemical features. The role of next-generation sequencing. ( 27144126 )
2016
9
Beneficial effect of feeding a ketogenic diet to mothers on brain development in their progeny with a murine model of pyruvate dehydrogenase complex deficiency. ( 27331005 )
2016
10
Complex genetic findings in a female patient with pyruvate dehydrogenase complex deficiency: Null mutations in the PDHX gene associated with unusual expression of the testis-specific PDHA2 gene in her somatic cells. ( 27343776 )
2016
11
Pyruvate dehydrogenase complex deficiency and its relationship with epilepsy frequency--An overview. ( 26354166 )
2015
12
Mild phenotype in a male with pyruvate dehydrogenase complex deficiency associated with novel hemizygous in-frame duplication of the E1α subunit gene (PDHA1). ( 23572181 )
2014
13
Energy substrate metabolism in pyruvate dehydrogenase complex deficiency. ( 24914713 )
2014
14
Somatic mosaicism for a novel PDHA1 mutation in a male with severe pyruvate dehydrogenase complex deficiency. ( 27896109 )
2014
15
Phenylbutyrate therapy for pyruvate dehydrogenase complex deficiency and lactic acidosis. ( 23467562 )
2013
16
The spectrum of pyruvate dehydrogenase complex deficiency: clinical, biochemical and genetic features in 371 patients. ( 22079328 )
2012
17
Intermittent-relapsing pyruvate dehydrogenase complex deficiency: a case with clinical, biochemical, and neuroradiological reversibility. ( 22142326 )
2012
18
The spectrum of pyruvate dehydrogenase complex deficiency: clinical, biochemical and genetic features in 371 patients. ( 22896851 )
2012
19
MRI features of 4 female patients with pyruvate dehydrogenase E1 alpha deficiency. ( 21723463 )
2011
20
Molecular characterization of 82 patients with pyruvate dehydrogenase complex deficiency. Structural implications of novel amino acid substitutions in E1 protein. ( 21914562 )
2011
21
Pyruvate dehydrogenase complex deficiency: four neurological phenotypes with differing pathogenesis. ( 20002125 )
2010
22
Mutational study in the PDHA1 gene of 40 patients suspected of pyruvate dehydrogenase complex deficiency. ( 20002461 )
2010
23
Somatic mosaicism for PDHA1 mutation in a male with pyruvate dehydrogenase complex deficiency. ( 20462777 )
2010
24
Liver-specific pyruvate dehydrogenase complex deficiency upregulates lipogenesis in adipose tissue and improves peripheral insulin sensitivity. ( 20835892 )
2010
25
Novel mutation (R263X) of the E1α subunit in pyruvate dehydrogenase complex deficiency. ( 20958858 )
2010
26
Pyruvate dehydrogenase complex deficiency caused by ubiquitination and proteasome-mediated degradation of the E1 subunit. ( 17923481 )
2008
27
Tissue-specific pyruvate dehydrogenase complex deficiency causes cardiac hypertrophy and sudden death of weaned male mice. ( 18586888 )
2008
28
Effect of pyruvate dehydrogenase complex deficiency on L-lysine production with Corynebacterium glutamicum. ( 17333167 )
2007
29
Brain MR imaging and proton MR spectroscopy in female mice with pyruvate dehydrogenase complex deficiency. ( 17342409 )
2007
30
Therapeutic potential of dichloroacetate for pyruvate dehydrogenase complex deficiency. ( 16725381 )
2006
31
Magnetic resonance spectroscopic investigation of mitochondrial fuel metabolism and energetics in cultured human fibroblasts: effects of pyruvate dehydrogenase complex deficiency and dichloroacetate. ( 16765624 )
2006
32
A Korean female patient with thiamine-responsive pyruvate dehydrogenase complex deficiency due to a novel point mutation (Y161C)in the PDHA1 gene. ( 17043409 )
2006
33
A family with pyruvate dehydrogenase complex deficiency due to a novel C>T substitution at nucleotide position 407 in exon 4 of the X-linked Epsilon1alpha gene. ( 15558317 )
2005
34
Diagnosis and molecular analysis of three male patients with thiamine-responsive pyruvate dehydrogenase complex deficiency. ( 12163191 )
2002
35
Thiamine-responsive pyruvate dehydrogenase deficiency in two patients caused by a point mutation (F205L and L216F) within the thiamine pyrophosphate binding region. ( 12379317 )
2002
36
Gender-specific occurrence of West syndrome in patients with pyruvate dehydrogenase complex deficiency. ( 11870584 )
2001
37
Caveats when considering ketogenic diets for the treatment of pyruvate dehydrogenase complex deficiency. ( 11241048 )
2001
38
Analysis of exonic mutations leading to exon skipping in patients with pyruvate dehydrogenase E1 alpha deficiency. ( 11102541 )
2000
39
Mutations in the X-linked pyruvate dehydrogenase (E1) alpha subunit gene (PDHA1) in patients with a pyruvate dehydrogenase complex deficiency. ( 10679936 )
2000
40
Concomitant administration of sodium dichloroacetate and thiamine in west syndrome caused by thiamine-responsive pyruvate dehydrogenase complex deficiency. ( 10567050 )
1999
41
Proton MR spectroscopy in a child with pyruvate dehydrogenase complex deficiency. ( 10402601 )
1999
42
Cerebral palsy and pyruvate dehydrogenase deficiency: identification of two new mutations in the E1alpha gene. ( 10486093 )
1999
43
Pyruvate dehydrogenase E1 alpha deficiency in a family: different clinical presentation in two siblings. ( 9686362 )
1998
44
Detection of a homozygous four base pair deletion in the protein X gene in a case of pyruvate dehydrogenase complex deficiency. ( 9467010 )
1998
45
Pyruvate dehydrogenase complex deficiency and absence of subunit X. ( 9501264 )
1998
46
Pyruvate dehydrogenase complex deficiency and altered respiratory chain function in a patient with Kearns-Sayre/MELAS overlap syndrome and A3243G mtDNA mutation. ( 9619647 )
1998
47
Arginine 302 mutations in the pyruvate dehydrogenase E1alpha subunit gene: identification of further patients and in vitro demonstration of pathogenicity. ( 9671272 )
1998
48
Biochemical and molecular analysis of an X-linked case of Leigh syndrome associated with thiamin-responsive pyruvate dehydrogenase deficiency. ( 9266390 )
1997
49
Biochemical and genetic studies of four patients with pyruvate dehydrogenase E1 alpha deficiency. ( 9187674 )
1997
50
Recurrent muscle weakness and ataxia in thiamine-responsive pyruvate dehydrogenase complex deficiency. ( 9075024 )
1997

Variations for Pyruvate Dehydrogenase E1-Alpha Deficiency

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

76 (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

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

6 (show top 50) (show all 459)
# Gene Variation Type Significance SNP ID Assembly Location
1 PDHA1 NM_000284.3(PDHA1): c.1167_1170delCAGT (p.Ser390Lysfs) deletion Pathogenic rs606231184 GRCh38 Chromosome X, 19359647: 19359650
2 PDHA1 NM_000284.3(PDHA1): c.1167_1170delCAGT (p.Ser390Lysfs) deletion Pathogenic rs606231184 GRCh37 Chromosome X, 19377765: 19377768
3 PDHA1 NM_000284.3(PDHA1): c.934_940delAGTAAGA (p.Ser312Valfs) deletion Pathogenic rs606231185 GRCh38 Chromosome X, 19358950: 19358956
4 PDHA1 NM_000284.3(PDHA1): c.934_940delAGTAAGA (p.Ser312Valfs) deletion Pathogenic rs606231185 GRCh37 Chromosome X, 19377068: 19377074
5 PDHA1 NM_001173454.1(PDHA1): c.1247G> A (p.Arg416His) single nucleotide variant Pathogenic rs137853250 GRCh37 Chromosome X, 19377731: 19377731
6 PDHA1 NM_001173454.1(PDHA1): c.1247G> A (p.Arg416His) single nucleotide variant Pathogenic rs137853250 GRCh38 Chromosome X, 19359613: 19359613
7 PDHA1 NM_000284.3(PDHA1): c.937_939del (p.Lys313del) deletion Pathogenic rs137853251 GRCh37 Chromosome X, 19377071: 19377073
8 PDHA1 NM_000284.3(PDHA1): c.937_939del (p.Lys313del) deletion Pathogenic rs137853251 GRCh38 Chromosome X, 19358953: 19358955
9 PDHA1 NM_000284.3(PDHA1): c.1159_1160delAA (p.Lys387Valfs) deletion Pathogenic rs606231186 GRCh38 Chromosome X, 19359639: 19359640
10 PDHA1 NM_000284.3(PDHA1): c.1159_1160delAA (p.Lys387Valfs) deletion Pathogenic rs606231186 GRCh37 Chromosome X, 19377757: 19377758
11 PDHA1 NM_000284.3(PDHA1): c.1073_1092del20 (p.Glu358Glyfs) deletion Pathogenic rs606231187 GRCh38 Chromosome X, 19359553: 19359572
12 PDHA1 NM_000284.3(PDHA1): c.1073_1092del20 (p.Glu358Glyfs) deletion Pathogenic rs606231187 GRCh37 Chromosome X, 19377671: 19377690
13 PDHA1 NM_000284.3(PDHA1) insertion Pathogenic rs606231188 GRCh38 Chromosome X, 19358913: 19358933
14 PDHA1 NM_000284.3(PDHA1) insertion Pathogenic rs606231188 GRCh37 Chromosome X, 19377031: 19377051
15 PDHA1 NM_000284.3(PDHA1): c.787C> G (p.Arg263Gly) single nucleotide variant Pathogenic rs137853259 GRCh37 Chromosome X, 19373831: 19373831
16 PDHA1 NM_000284.3(PDHA1): c.787C> G (p.Arg263Gly) single nucleotide variant Pathogenic rs137853259 GRCh38 Chromosome X, 19355713: 19355713
17 PDHA1 NM_000284.3(PDHA1): c.904C> T (p.Arg302Cys) single nucleotide variant Pathogenic rs137853252 GRCh37 Chromosome X, 19377038: 19377038
18 PDHA1 NM_000284.3(PDHA1): c.904C> T (p.Arg302Cys) single nucleotide variant Pathogenic rs137853252 GRCh38 Chromosome X, 19358920: 19358920
19 PDHA1 NM_000284.3(PDHA1): c.1142_1145dupATCA (p.Trp383Serfs) duplication Pathogenic rs606231189 GRCh38 Chromosome X, 19359622: 19359625
20 PDHA1 NM_000284.3(PDHA1): c.1142_1145dupATCA (p.Trp383Serfs) duplication Pathogenic rs606231189 GRCh37 Chromosome X, 19377740: 19377743
21 PDHA1 NM_000284.3(PDHA1): c.773A> C (p.Asp258Ala) single nucleotide variant Pathogenic rs137853253 GRCh37 Chromosome X, 19373817: 19373817
22 PDHA1 NM_000284.3(PDHA1): c.773A> C (p.Asp258Ala) single nucleotide variant Pathogenic rs137853253 GRCh38 Chromosome X, 19355699: 19355699
23 PDHA1 NM_000284.3(PDHA1): c.615C> G (p.Phe205Leu) single nucleotide variant Pathogenic rs137853254 GRCh37 Chromosome X, 19373478: 19373478
24 PDHA1 NM_000284.3(PDHA1): c.615C> G (p.Phe205Leu) single nucleotide variant Pathogenic rs137853254 GRCh38 Chromosome X, 19355360: 19355360
25 PDHA1 NM_000284.3(PDHA1): c.727T> A (p.Tyr243Asn) single nucleotide variant Pathogenic rs137853255 GRCh37 Chromosome X, 19373590: 19373590
26 PDHA1 NM_000284.3(PDHA1): c.727T> A (p.Tyr243Asn) single nucleotide variant Pathogenic rs137853255 GRCh38 Chromosome X, 19355472: 19355472
27 PDHA1 NM_000284.3(PDHA1): c.943G> A (p.Asp315Asn) single nucleotide variant Pathogenic rs137853256 GRCh37 Chromosome X, 19377077: 19377077
28 PDHA1 NM_000284.3(PDHA1): c.943G> A (p.Asp315Asn) single nucleotide variant Pathogenic rs137853256 GRCh38 Chromosome X, 19358959: 19358959
29 PDHA1 NM_000284.3(PDHA1): c.844A> C (p.Met282Leu) single nucleotide variant Benign rs2229137 GRCh37 Chromosome X, 19375782: 19375782
30 PDHA1 NM_000284.3(PDHA1): c.844A> C (p.Met282Leu) single nucleotide variant Benign rs2229137 GRCh38 Chromosome X, 19357664: 19357664
31 PDHA1 NM_000284.3(PDHA1): c.861_862insT (p.Arg288Serfs) insertion Pathogenic rs606231190 GRCh38 Chromosome X, 19357681: 19357682
32 PDHA1 NM_000284.3(PDHA1): c.861_862insT (p.Arg288Serfs) insertion Pathogenic rs606231190 GRCh37 Chromosome X, 19375799: 19375800
33 PDHA1 NM_000284.3(PDHA1): c.29G> C (p.Arg10Pro) single nucleotide variant Pathogenic rs137853257 GRCh37 Chromosome X, 19362184: 19362184
34 PDHA1 NM_000284.3(PDHA1): c.29G> C (p.Arg10Pro) single nucleotide variant Pathogenic rs137853257 GRCh38 Chromosome X, 19344066: 19344066
35 PDHA1 PDHA1, 13-BP INS, EX10 insertion Pathogenic
36 PDHA1 NM_000284.3(PDHA1) duplication Pathogenic rs606231191 GRCh38 Chromosome X, 19359554: 19359589
37 PDHA1 NM_000284.3(PDHA1) duplication Pathogenic rs606231191 GRCh37 Chromosome X, 19377672: 19377707
38 PDHA1 NM_000284.3(PDHA1): c.863G> A (p.Arg288His) single nucleotide variant Pathogenic rs137853258 GRCh37 Chromosome X, 19375801: 19375801
39 PDHA1 NM_000284.3(PDHA1): c.863G> A (p.Arg288His) single nucleotide variant Pathogenic rs137853258 GRCh38 Chromosome X, 19357683: 19357683
40 PDHA1 NM_000284.3(PDHA1): c.*79_*90dup duplication Pathogenic rs1555935690 GRCh38 Chromosome X, 19359732: 19359743
41 PDHA1 NM_000284.3(PDHA1): c.*79_*90dup duplication Pathogenic rs1555935690 GRCh37 Chromosome X, 19377850: 19377861
42 PDHA1 NM_000284.3(PDHA1): c.648A> C (p.Leu216Phe) single nucleotide variant Pathogenic rs121917898 GRCh37 Chromosome X, 19373511: 19373511
43 PDHA1 NM_000284.3(PDHA1): c.648A> C (p.Leu216Phe) single nucleotide variant Pathogenic rs121917898 GRCh38 Chromosome X, 19355393: 19355393
44 DLAT NM_001931.4(DLAT): c.128C> T (p.Ala43Val) single nucleotide variant Benign rs2303436 GRCh37 Chromosome 11, 111896324: 111896324
45 DLAT NM_001931.4(DLAT): c.128C> T (p.Ala43Val) single nucleotide variant Benign rs2303436 GRCh38 Chromosome 11, 112025600: 112025600
46 DLAT NM_001931.4(DLAT): c.1351G> A (p.Asp451Asn) single nucleotide variant Benign rs10891314 GRCh37 Chromosome 11, 111916647: 111916647
47 DLAT NM_001931.4(DLAT): c.1351G> A (p.Asp451Asn) single nucleotide variant Benign rs10891314 GRCh38 Chromosome 11, 112045923: 112045923
48 DLAT NM_001931.4(DLAT): c.953T> C (p.Val318Ala) single nucleotide variant Benign rs627441 GRCh37 Chromosome 11, 111908162: 111908162
49 DLAT NM_001931.4(DLAT): c.953T> C (p.Val318Ala) single nucleotide variant Benign rs627441 GRCh38 Chromosome 11, 112037438: 112037438
50 PDHB NM_000925.3(PDHB): c.438G> A (p.Gly146=) single nucleotide variant Benign rs1126551 GRCh37 Chromosome 3, 58416535: 58416535

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:

38
# 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 12)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.22 HIBCH PDHA1 PDHB PDHX
2
Show member pathways
12.16 PDHA1 PDHB PDHX
3
Show member pathways
11.82 HIBCH PDHA1 PDHB
4
Show member pathways
11.55 PDHA1 PDHB PDHX
5
Show member pathways
11.51 PDHA1 PDHB
6 11.49 PDHA1 PDHB
7 11.46 PDHA1 PDHB
8 11.29 HIBCH PDHA1 PDHX
9 11.25 PDHA1 PDHB
10
Show member pathways
10.99 PDHA1 PDHB
11
Show member pathways
10.95 PDHA1 PDHB PDHX
12
Show member pathways
10.41 PDHA1 PDHB PDHX

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 9.46 HIBCH PDHA1 PDHB PDHX
2 mitochondrial matrix GO:0005759 9.26 HIBCH PDHA1 PDHB PDHX
3 pyruvate dehydrogenase complex GO:0045254 8.8 PDHA1 PDHB PDHX

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

# Name GO ID Score Top Affiliating Genes
1 carbohydrate metabolic process GO:0005975 9.32 PDHA1 PDHB
2 glucose metabolic process GO:0006006 9.26 PDHA1 PDHB
3 tricarboxylic acid cycle GO:0006099 9.16 PDHA1 PDHB
4 acetyl-CoA biosynthetic process from pyruvate GO:0006086 8.96 PDHA1 PDHB
5 mitochondrial acetyl-CoA biosynthetic process from pyruvate GO:0061732 8.8 PDHA1 PDHB PDHX

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 PDHA1 PDHB
2 pyruvate dehydrogenase activity GO:0004738 8.96 PDHA1 PDHB
3 pyruvate dehydrogenase (NAD+) activity GO:0034604 8.8 PDHA1 PDHB PDHX

Sources for Pyruvate Dehydrogenase E1-Alpha Deficiency

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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