PDHPD
MCID: PYR018
MIFTS: 32

Pyruvate Dehydrogenase Phosphatase Deficiency (PDHPD)

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

Aliases & Classifications for Pyruvate Dehydrogenase Phosphatase Deficiency

MalaCards integrated aliases for Pyruvate Dehydrogenase Phosphatase Deficiency:

Name: Pyruvate Dehydrogenase Phosphatase Deficiency 57 20 58 72 36 29 13 6 39 70
Lactic Acidemia with Pyruvate Dehydrogenase Phosphatase Deficiency 57 20
Pdh Phosphatase Deficiency 58
Pdp Deficiency 72
Pdhpd 57

Characteristics:

Orphanet epidemiological data:

58
pyruvate dehydrogenase phosphatase deficiency
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal; Age of death: adolescent,late childhood;

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy


HPO:

31
pyruvate dehydrogenase phosphatase deficiency:
Inheritance autosomal recessive inheritance
Onset and clinical course infantile onset


Classifications:

Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism


External Ids:

OMIM® 57 608782
OMIM Phenotypic Series 57 PS312170
KEGG 36 H01996
MESH via Orphanet 45 C536258
ICD10 via Orphanet 33 E74.4
UMLS via Orphanet 71 C1837429
Orphanet 58 ORPHA79246
MedGen 41 C1837429
UMLS 70 C1837429

Summaries for Pyruvate Dehydrogenase Phosphatase Deficiency

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 79246 Definition Pyruvate dehydrogenase phosphatase deficiency is a very rare subtype of pyruvate dehydrogenase deficiency (PDHD, see this term) characterized by lactic acidemia in the neonatal period. Epidemiology Prevalence is unknown but this form of PDHD appears to be very rare, with only three patients reported. Clinical description All three patients presented in the newborn period with lactic acidosis and hypotonia. Two siblings from one family have had a prolonged course on a ketogenic diet, surviving into teenage years with exercise intolerance and mild developmental delay. The third patient died at age 6 months. Etiology The disorder is caused by mutations in the PDP1 gene (8q22.1) encoding pyruvate dehyrogenase phosphatase isoform 1, an enzyme which regulates the activity of the pyruvate dehydrogenase complex. Genetic counseling The pattern of inheritance is autosomal recessive.

MalaCards based summary : Pyruvate Dehydrogenase Phosphatase Deficiency, also known as lactic acidemia with pyruvate dehydrogenase phosphatase deficiency, is related to lactic acidosis and metabolic acidosis, and has symptoms including seizures and gait ataxia. An important gene associated with Pyruvate Dehydrogenase Phosphatase Deficiency is PDP1 (Pyruvate Dehydrogenase Phosphatase Catalytic Subunit 1), and among its related pathways/superpathways are Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins. and Pyruvate metabolism and Citric Acid (TCA) cycle. Affiliated tissues include brain and skin, and related phenotypes are decreased activity of the pyruvate dehydrogenase complex and neonatal hypotonia

OMIM® : 57 Pyruvate dehydrogenase phosphatase deficiency (PDHPD) is an autosomal recessive disorder of pyruvate metabolism characterized by neonatal/infantile and childhood lactic acidosis, normal lactate to pyruvate ratio, elevated plasma alanine, delayed psychomotor development, epileptic encephalopathy, and hypotonia (summary by Bedoyan et al., 2019). For a general phenotypic description and a discussion of genetic heterogeneity of pyruvate dehydrogenase (PDH) deficiency, see 312170. (608782) (Updated 05-Apr-2021)

KEGG : 36 Pyruvate dehydrogenase phosphatase (PDP) deficiency has previously been confirmed only in a few cases. PDP is an enzyme which regulates the activity of the pyruvate dehydrogenase complex. It has been reported that the mutations in PDP1 gene result in lactic acidemia, progressive neurodegeneration, and seizure activity, culminating in early death.

UniProtKB/Swiss-Prot : 72 Pyruvate dehydrogenase phosphatase deficiency: Results in lactic acidosis leading to neurological dysfunction.

Wikipedia : 73 Pyruvate dehyrogenase phosphatase catalytic subunit 1 (PDPC 1), also known as protein phosphatase 2C, is... more...

Related Diseases for Pyruvate Dehydrogenase Phosphatase Deficiency

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

# Related Disease Score Top Affiliating Genes
1 lactic acidosis 29.7 PDP1 PDHB
2 metabolic acidosis 10.1
3 hypotonia 10.1
4 leigh syndrome 9.5 PDP1 PDHB

Symptoms & Phenotypes for Pyruvate Dehydrogenase Phosphatase Deficiency

Human phenotypes related to Pyruvate Dehydrogenase Phosphatase Deficiency:

58 31 (show all 19)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 decreased activity of the pyruvate dehydrogenase complex 58 31 hallmark (90%) Very frequent (99-80%) HP:0002928
2 neonatal hypotonia 58 31 frequent (33%) Frequent (79-30%) HP:0001319
3 increased serum lactate 58 31 frequent (33%) Frequent (79-30%) HP:0002151
4 lactic acidosis 58 31 frequent (33%) Frequent (79-30%) HP:0003128
5 mild global developmental delay 58 31 frequent (33%) Frequent (79-30%) HP:0011342
6 brain imaging abnormality 58 31 frequent (33%) Frequent (79-30%) HP:0410263
7 hyperalaninemia 58 31 frequent (33%) Frequent (79-30%) HP:0003348
8 muscular hypotonia of the trunk 58 31 frequent (33%) Frequent (79-30%) HP:0008936
9 hyperprolinemia 58 31 frequent (33%) Frequent (79-30%) HP:0008358
10 lacticaciduria 58 31 frequent (33%) Frequent (79-30%) HP:0003648
11 focal hyperintensity of cerebral white matter on mri 58 31 frequent (33%) Frequent (79-30%) HP:0040328
12 intellectual disability 31 HP:0001249
13 nystagmus 31 HP:0000639
14 dysphagia 31 HP:0002015
15 global developmental delay 31 HP:0001263
16 gait ataxia 31 HP:0002066
17 generalized hypotonia 31 HP:0001290
18 seizure 31 HP:0001250
19 hypotonia 31 HP:0001252

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
seizures
developmental delay
mental retardation
ataxic gait
low densities in the basal ganglia similar to leigh syndrome

Abdomen Gastrointestinal:
dysphagia
poor oral feeding

Muscle Soft Tissue:
hypotonia

Head And Neck Eyes:
nystagmus

Metabolic Features:
lactic acidosis
normal lactate to pyruvate ratio
elevated alanine

Laboratory Abnormalities:
decreased activity of the pyruvate dehydrogenase (pdh) complex
decreased activity of the pdh phosphatase

Clinical features from OMIM®:

608782 (Updated 05-Apr-2021)

UMLS symptoms related to Pyruvate Dehydrogenase Phosphatase Deficiency:


seizures; gait ataxia

Drugs & Therapeutics for Pyruvate Dehydrogenase Phosphatase Deficiency

Search Clinical Trials , NIH Clinical Center for Pyruvate Dehydrogenase Phosphatase Deficiency

Genetic Tests for Pyruvate Dehydrogenase Phosphatase Deficiency

Genetic tests related to Pyruvate Dehydrogenase Phosphatase Deficiency:

# Genetic test Affiliating Genes
1 Pyruvate Dehydrogenase Phosphatase Deficiency 29 PDP1

Anatomical Context for Pyruvate Dehydrogenase Phosphatase Deficiency

MalaCards organs/tissues related to Pyruvate Dehydrogenase Phosphatase Deficiency:

40
Brain, Skin

Publications for Pyruvate Dehydrogenase Phosphatase Deficiency

Articles related to Pyruvate Dehydrogenase Phosphatase Deficiency:

(show all 12)
# Title Authors PMID Year
1
Pyruvate dehydrogenase phosphatase 1 (PDP1) null mutation produces a lethal infantile phenotype. 6 57 61
19184109 2009
2
Pyruvate dehydrogenase phosphatase deficiency: identification of the first mutation in two brothers and restoration of activity by protein complementation. 61 57 6
15855260 2005
3
A novel null mutation in the pyruvate dehydrogenase phosphatase catalytic subunit gene (PDP1) causing pyruvate dehydrogenase complex deficiency. 6 57
31392110 2019
4
Pyruvate dehydrogenase phosphatase deficiency: a cause of congenital chronic lactic acidosis in infancy. 57 61
172850 1975
5
Decrease of pyruvate dehydrogenase phosphatase activity in patients with congenital lactic acidemia. 57
1327585 1992
6
Detection of pyruvate metabolism disorders by culture of skin fibroblasts with dichloroacetate. 57
2839811 1988
7
Abnormal activation of pyruvate dehydrogenase in Leigh disease fibroblasts. 57
7200213 1982
8
Defective activation of the pyruvate dehydrogenase complex in subacute necrotizing encephalomyelopathy (Leigh disease). 57
119480 1979
9
Identification of a canine model of pyruvate dehydrogenase phosphatase 1 deficiency. 61
17095275 2007
10
Pyruvate dehydrogenase phosphatase deficiency: orphan disease or an under-diagnosed condition? 61
16574315 2006
11
[Pyruvate dehydrogenase phosphatase deficiency]. 61
9590064 1998
12
Lactic acidosis due to a defect in the pyruvate dehydrogenase complex: a possible brain pyruvate dehydrogenase phosphatase deficiency. 61
215904 1978

Variations for Pyruvate Dehydrogenase Phosphatase Deficiency

ClinVar genetic disease variations for Pyruvate Dehydrogenase Phosphatase Deficiency:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 PDP1 NM_018444.4(PDP1):c.851_853del (p.Leu284del) Deletion Pathogenic 4663 rs1554572756 GRCh37: 8:94935137-94935139
GRCh38: 8:93922909-93922911
2 PDP1 NM_018444.4(PDP1):c.277G>T (p.Glu93Ter) SNV Pathogenic 4664 rs267606938 GRCh37: 8:94934564-94934564
GRCh38: 8:93922336-93922336
3 PDP1 NM_018444.4(PDP1):c.500dup (p.Leu167fs) Duplication Pathogenic 982568 GRCh37: 8:94934784-94934785
GRCh38: 8:93922556-93922557
4 PDHB NM_000925.4(PDHB):c.501G>T (p.Gly167=) SNV Uncertain significance 722700 rs759053641 GRCh37: 3:58416472-58416472
GRCh38: 3:58430745-58430745
5 PDP1 NM_018444.4(PDP1):c.*724del Deletion Uncertain significance 363953 rs886063179 GRCh37: 8:94936619-94936619
GRCh38: 8:93924391-93924391
6 PDP1 NM_018444.4(PDP1):c.*1661del Deletion Uncertain significance 363967 rs60316663 GRCh37: 8:94937550-94937550
GRCh38: 8:93925322-93925322
7 PDP1 NM_018444.4(PDP1):c.*898_*900CTT[1] Microsatellite Uncertain significance 363956 rs756226872 GRCh37: 8:94936799-94936801
GRCh38: 8:93924571-93924573
8 PDP1 NM_018444.4(PDP1):c.*1649_*1650insG Insertion Uncertain significance 363968 rs886063184 GRCh37: 8:94937550-94937551
GRCh38: 8:93925322-93925323
9 PDP1 NM_018444.3(PDP1):c.-273T>A SNV Benign 369617 rs4469422 GRCh37: 8:94929079-94929079
GRCh38: 8:93916851-93916851

Expression for Pyruvate Dehydrogenase Phosphatase Deficiency

Search GEO for disease gene expression data for Pyruvate Dehydrogenase Phosphatase Deficiency.

Pathways for Pyruvate Dehydrogenase Phosphatase Deficiency

GO Terms for Pyruvate Dehydrogenase Phosphatase Deficiency

Cellular components related to Pyruvate Dehydrogenase Phosphatase Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrial matrix GO:0005759 8.62 PDP1 PDHB

Molecular functions related to Pyruvate Dehydrogenase Phosphatase Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 catalytic activity GO:0003824 8.62 PDP1 PDHB

Sources for Pyruvate Dehydrogenase Phosphatase 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 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
Content
Loading form....