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 phenotypic variability 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 lactic acidosis and leigh syndrome, 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

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 global developmental delay 60 33 frequent (33%) Frequent (79-30%) HP:0001263
12 microcephaly 60 33 frequent (33%) Frequent (79-30%) HP:0000252
13 intrauterine growth retardation 60 33 frequent (33%) Frequent (79-30%) HP:0001511
14 choreoathetosis 60 33 frequent (33%) Frequent (79-30%) HP:0001266
15 aplasia/hypoplasia of the corpus callosum 60 33 frequent (33%) Frequent (79-30%) HP:0007370
16 tachypnea 60 33 frequent (33%) Frequent (79-30%) HP:0002789
17 osteolytic defects of the middle phalanx of the 4th toe 60 33 frequent (33%) Frequent (79-30%) HP:0100453
18 abnormal pyramidal sign 33 frequent (33%) HP:0007256
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 narrow face 60 33 occasional (7.5%) Occasional (29-5%) HP:0000275
31 upslanted palpebral fissure 60 33 occasional (7.5%) Occasional (29-5%) HP:0000582
32 cerebral palsy 60 33 occasional (7.5%) Occasional (29-5%) HP:0100021
33 trigonocephaly 60 33 occasional (7.5%) Occasional (29-5%) HP:0000243
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 abnormal pyramidal signs 60 Frequent (79-30%)
39 anteverted nares 33 HP:0000463
40 growth delay 60 Very frequent (99-80%)
41 increased serum lactate 33 HP:0002151
42 generalized hypotonia 33 HP:0001290
43 cerebral atrophy 33 HP:0002059
44 small for gestational age 33 HP:0001518
45 hyperalaninemia 33 HP:0003348
46 episodic ataxia 33 HP:0002131
47 increased csf lactate 33 HP:0002490
48 severe lactic acidosis 33 HP:0004900
49 decreased activity of the pyruvate dehydrogenase complex 33 HP:0002928
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 all 38)
# Title Authors Year
1
Pyruvate dehydrogenase complex deficiency is linked to regulatory loop disorder in the αV138M variant of human pyruvate dehydrogenase. ( 29970614 )
2018
2
Efficacy of ketogenic diet for pyruvate dehydrogenase complex deficiency. ( 30407699 )
2018
3
Ketogenic diet in pyruvate dehydrogenase complex deficiency: short- and long-term outcomes. ( 28101805 )
2017
4
Thiamine Responsive Pyruvate Dehydrogenase Complex Deficiency: A Potentially Treatable Cause of Leigh's Disease. ( 29204204 )
2017
5
Prenatal presentation of pyruvate dehydrogenase complex deficiency. ( 27026023 )
2016
6
Difficulties in recognition of pyruvate dehydrogenase complex deficiency on the basis of clinical and biochemical features. The role of next-generation sequencing. ( 27144126 )
2016
7
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
8
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
9
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
10
Energy substrate metabolism in pyruvate dehydrogenase complex deficiency. ( 24914713 )
2014
11
Somatic mosaicism for a novel PDHA1 mutation in a male with severe pyruvate dehydrogenase complex deficiency. ( 27896109 )
2014
12
The spectrum of pyruvate dehydrogenase complex deficiency: clinical, biochemical and genetic features in 371 patients. ( 22079328 )
2012
13
The spectrum of pyruvate dehydrogenase complex deficiency: clinical, biochemical and genetic features in 371 patients. ( 22896851 )
2012
14
MRI features of 4 female patients with pyruvate dehydrogenase E1 alpha deficiency. ( 21723463 )
2011
15
Somatic mosaicism for PDHA1 mutation in a male with pyruvate dehydrogenase complex deficiency. ( 20462777 )
2010
16
Liver-specific pyruvate dehydrogenase complex deficiency upregulates lipogenesis in adipose tissue and improves peripheral insulin sensitivity. ( 20835892 )
2010
17
Tissue-specific pyruvate dehydrogenase complex deficiency causes cardiac hypertrophy and sudden death of weaned male mice. ( 18586888 )
2008
18
Effect of pyruvate dehydrogenase complex deficiency on L-lysine production with Corynebacterium glutamicum. ( 17333167 )
2007
19
Therapeutic potential of dichloroacetate for pyruvate dehydrogenase complex deficiency. ( 16725381 )
2006
20
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
21
Diagnosis and molecular analysis of three male patients with thiamine-responsive pyruvate dehydrogenase complex deficiency. ( 12163191 )
2002
22
Caveats when considering ketogenic diets for the treatment of pyruvate dehydrogenase complex deficiency. ( 11241048 )
2001
23
Analysis of exonic mutations leading to exon skipping in patients with pyruvate dehydrogenase E1 alpha deficiency. ( 11102541 )
2000
24
Proton MR spectroscopy in a child with pyruvate dehydrogenase complex deficiency. ( 10402601 )
1999
25
Pyruvate dehydrogenase E1 alpha deficiency in a family: different clinical presentation in two siblings. ( 9686362 )
1998
26
Biochemical and genetic studies of four patients with pyruvate dehydrogenase E1 alpha deficiency. ( 9187674 )
1997
27
Recurrent muscle weakness and ataxia in thiamine-responsive pyruvate dehydrogenase complex deficiency. ( 9075024 )
1997
28
Pyruvate dehydrogenase complex deficiency with multiple minor anomalies. ( 9141261 )
1997
29
Leigh syndrome due to pyruvate dehydrogenase E1 alpha deficiency (point mutation R263G) in a Spanish boy. ( 8982956 )
1996
30
Therapeutic efficacy of a case of pyruvate dehydrogenase complex deficiency monitored by localized proton magnetic resonance spectroscopy. ( 8656986 )
1996
31
Pyruvate dehydrogenase E1 alpha deficiency: males and females differ yet again. ( 7887408 )
1995
32
A novel mutation (P316L) in a female with pyruvate dehydrogenase E1 alpha deficiency. ( 8535453 )
1995
33
Neuropathological findings of a patient with pyruvate dehydrogenase E1 alpha deficiency presenting as a cerebral lactic acidosis. ( 8337946 )
1993
34
Pyruvate dehydrogenase E1 alpha deficiency. ( 1528021 )
1992
35
A mutation in the E1 alpha subunit of pyruvate dehydrogenase associated with variable expression of pyruvate dehydrogenase complex deficiency. ( 1508605 )
1992
36
Characterization of the mutations in three patients with pyruvate dehydrogenase E1 alpha deficiency. ( 1909401 )
1991
37
Pyruvate dehydrogenase complex deficiency: biochemical and immunoblot analysis of cultured skin fibroblasts. ( 2513771 )
1989
38
The clinical and biochemical spectrum of human pyruvate dehydrogenase complex deficiency. ( 2517465 )
1989

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 457)
# Gene Variation Type Significance SNP ID Assembly Location
1 PDHA1 NM_000284.3(PDHA1): c.422G> A (p.Arg141Gln) single nucleotide variant Pathogenic rs794729213 GRCh37 Chromosome X, 19371203: 19371203
2 PDHA1 NM_000284.3(PDHA1): c.422G> A (p.Arg141Gln) single nucleotide variant Pathogenic rs794729213 GRCh38 Chromosome X, 19353085: 19353085
3 DLD NM_000108.4(DLD): c.100A> G (p.Thr34Ala) single nucleotide variant Uncertain significance rs138002793 GRCh37 Chromosome 7, 107533705: 107533705
4 DLD NM_000108.4(DLD): c.100A> G (p.Thr34Ala) single nucleotide variant Uncertain significance rs138002793 GRCh38 Chromosome 7, 107893260: 107893260
5 DLD NM_000108.4(DLD): c.763A> C (p.Met255Leu) single nucleotide variant Uncertain significance rs533405046 GRCh37 Chromosome 7, 107556029: 107556029
6 DLD NM_000108.4(DLD): c.763A> C (p.Met255Leu) single nucleotide variant Uncertain significance rs533405046 GRCh38 Chromosome 7, 107915584: 107915584
7 DLAT NM_001931.4(DLAT): c.572C> T (p.Ala191Val) single nucleotide variant Conflicting interpretations of pathogenicity rs200500508 GRCh38 Chromosome 11, 112028857: 112028857
8 DLAT NM_001931.4(DLAT): c.572C> T (p.Ala191Val) single nucleotide variant Conflicting interpretations of pathogenicity rs200500508 GRCh37 Chromosome 11, 111899581: 111899581
9 PDHX NM_003477.2(PDHX): c.-23C> A single nucleotide variant Benign/Likely benign rs201033364 GRCh38 Chromosome 11, 34916633: 34916633
10 PDHX NM_003477.2(PDHX): c.-23C> A single nucleotide variant Benign/Likely benign rs201033364 GRCh37 Chromosome 11, 34938180: 34938180
11 PDHX NM_003477.2(PDHX): c.749C> T (p.Thr250Ile) single nucleotide variant Uncertain significance rs146876119 GRCh38 Chromosome 11, 34966747: 34966747
12 PDHX NM_003477.2(PDHX): c.749C> T (p.Thr250Ile) single nucleotide variant Uncertain significance rs146876119 GRCh37 Chromosome 11, 34988294: 34988294
13 PDHX NM_003477.2(PDHX): c.1129A> G (p.Ile377Val) single nucleotide variant Uncertain significance rs75430333 GRCh38 Chromosome 11, 34984675: 34984675
14 PDHX NM_003477.2(PDHX): c.1129A> G (p.Ile377Val) single nucleotide variant Uncertain significance rs75430333 GRCh37 Chromosome 11, 35006222: 35006222
15 PDHX NM_003477.2(PDHX): c.1333T> G (p.Phe445Val) single nucleotide variant Uncertain significance rs147948716 GRCh38 Chromosome 11, 34994999: 34994999
16 PDHX NM_003477.2(PDHX): c.1333T> G (p.Phe445Val) single nucleotide variant Uncertain significance rs147948716 GRCh37 Chromosome 11, 35016546: 35016546
17 PDHA1 NM_000284.3(PDHA1): c.214C> T (p.Arg72Cys) single nucleotide variant Pathogenic/Likely pathogenic rs863224148 GRCh37 Chromosome X, 19368151: 19368151
18 PDHA1 NM_000284.3(PDHA1): c.214C> T (p.Arg72Cys) single nucleotide variant Pathogenic/Likely pathogenic rs863224148 GRCh38 Chromosome X, 19350033: 19350033
19 PDHA1 NM_000284.3(PDHA1): c.506C> T (p.Ala169Val) single nucleotide variant Pathogenic rs863224150 GRCh38 Chromosome X, 19353169: 19353169
20 PDHA1 NM_000284.3(PDHA1): c.506C> T (p.Ala169Val) single nucleotide variant Pathogenic rs863224150 GRCh37 Chromosome X, 19371287: 19371287
21 PDHA1 NM_000284.3(PDHA1): c.910C> T (p.Arg304Ter) single nucleotide variant Pathogenic rs863224146 GRCh37 Chromosome X, 19377044: 19377044
22 PDHA1 NM_000284.3(PDHA1): c.910C> T (p.Arg304Ter) single nucleotide variant Pathogenic rs863224146 GRCh38 Chromosome X, 19358926: 19358926
23 PDHA1 NM_000284.3(PDHA1): c.1132C> T (p.Arg378Cys) single nucleotide variant Pathogenic rs863224147 GRCh37 Chromosome X, 19377730: 19377730
24 PDHA1 NM_000284.3(PDHA1): c.1132C> T (p.Arg378Cys) single nucleotide variant Pathogenic rs863224147 GRCh38 Chromosome X, 19359612: 19359612
25 PDHA1 NM_000284.3(PDHA1): c.1167_1170delCAGT (p.Ser390Lysfs) deletion Pathogenic rs606231184 GRCh38 Chromosome X, 19359647: 19359650
26 PDHA1 NM_000284.3(PDHA1): c.1167_1170delCAGT (p.Ser390Lysfs) deletion Pathogenic rs606231184 GRCh37 Chromosome X, 19377765: 19377768
27 PDHA1 NM_000284.3(PDHA1): c.934_940delAGTAAGA (p.Ser312Valfs) deletion Pathogenic rs606231185 GRCh38 Chromosome X, 19358950: 19358956
28 PDHA1 NM_000284.3(PDHA1): c.934_940delAGTAAGA (p.Ser312Valfs) deletion Pathogenic rs606231185 GRCh37 Chromosome X, 19377068: 19377074
29 PDHA1 NM_001173454.1(PDHA1): c.1247G> A (p.Arg416His) single nucleotide variant Pathogenic rs137853250 GRCh37 Chromosome X, 19377731: 19377731
30 PDHA1 NM_001173454.1(PDHA1): c.1247G> A (p.Arg416His) single nucleotide variant Pathogenic rs137853250 GRCh38 Chromosome X, 19359613: 19359613
31 PDHA1 NM_000284.3(PDHA1): c.937_939del (p.Lys313del) deletion Pathogenic rs137853251 GRCh37 Chromosome X, 19377071: 19377073
32 PDHA1 NM_000284.3(PDHA1): c.937_939del (p.Lys313del) deletion Pathogenic rs137853251 GRCh38 Chromosome X, 19358953: 19358955
33 PDHA1 NM_000284.3(PDHA1): c.1159_1160delAA (p.Lys387Valfs) deletion Pathogenic rs606231186 GRCh38 Chromosome X, 19359639: 19359640
34 PDHA1 NM_000284.3(PDHA1): c.1159_1160delAA (p.Lys387Valfs) deletion Pathogenic rs606231186 GRCh37 Chromosome X, 19377757: 19377758
35 PDHA1 NM_000284.3(PDHA1): c.1073_1092del20 (p.Glu358Glyfs) deletion Pathogenic rs606231187 GRCh38 Chromosome X, 19359553: 19359572
36 PDHA1 NM_000284.3(PDHA1): c.1073_1092del20 (p.Glu358Glyfs) deletion Pathogenic rs606231187 GRCh37 Chromosome X, 19377671: 19377690
37 PDHA1 NM_000284.3(PDHA1) insertion Pathogenic rs606231188 GRCh38 Chromosome X, 19358913: 19358933
38 PDHA1 NM_000284.3(PDHA1) insertion Pathogenic rs606231188 GRCh37 Chromosome X, 19377031: 19377051
39 PDHA1 NM_000284.3(PDHA1): c.787C> G (p.Arg263Gly) single nucleotide variant Pathogenic rs137853259 GRCh37 Chromosome X, 19373831: 19373831
40 PDHA1 NM_000284.3(PDHA1): c.787C> G (p.Arg263Gly) single nucleotide variant Pathogenic rs137853259 GRCh38 Chromosome X, 19355713: 19355713
41 PDHA1 NM_000284.3(PDHA1): c.904C> T (p.Arg302Cys) single nucleotide variant Pathogenic/Likely pathogenic rs137853252 GRCh37 Chromosome X, 19377038: 19377038
42 PDHA1 NM_000284.3(PDHA1): c.904C> T (p.Arg302Cys) single nucleotide variant Pathogenic/Likely pathogenic rs137853252 GRCh38 Chromosome X, 19358920: 19358920
43 PDHA1 NM_000284.3(PDHA1): c.1142_1145dupATCA (p.Trp383Serfs) duplication Pathogenic rs606231189 GRCh38 Chromosome X, 19359622: 19359625
44 PDHA1 NM_000284.3(PDHA1): c.1142_1145dupATCA (p.Trp383Serfs) duplication Pathogenic rs606231189 GRCh37 Chromosome X, 19377740: 19377743
45 PDHA1 NM_000284.3(PDHA1): c.773A> C (p.Asp258Ala) single nucleotide variant Pathogenic rs137853253 GRCh37 Chromosome X, 19373817: 19373817
46 PDHA1 NM_000284.3(PDHA1): c.773A> C (p.Asp258Ala) single nucleotide variant Pathogenic rs137853253 GRCh38 Chromosome X, 19355699: 19355699
47 PDHA1 NM_000284.3(PDHA1): c.615C> G (p.Phe205Leu) single nucleotide variant Pathogenic rs137853254 GRCh37 Chromosome X, 19373478: 19373478
48 PDHA1 NM_000284.3(PDHA1): c.615C> G (p.Phe205Leu) single nucleotide variant Pathogenic rs137853254 GRCh38 Chromosome X, 19355360: 19355360
49 PDHA1 NM_000284.3(PDHA1): c.727T> A (p.Tyr243Asn) single nucleotide variant Pathogenic rs137853255 GRCh37 Chromosome X, 19373590: 19373590
50 PDHA1 NM_000284.3(PDHA1): c.727T> A (p.Tyr243Asn) single nucleotide variant Pathogenic rs137853255 GRCh38 Chromosome X, 19355472: 19355472

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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