MCID: PYR037
MIFTS: 39

Pyruvate Carboxylase Deficiency

Categories: Genetic diseases, Rare diseases, Metabolic diseases

Aliases & Classifications for Pyruvate Carboxylase Deficiency

MalaCards integrated aliases for Pyruvate Carboxylase Deficiency:

Name: Pyruvate Carboxylase Deficiency 54 23 50 24 25 56 71 29 13
Pyruvate Carboxylase Deficiency Disease 12 25 42 69
Leigh Necrotizing Encephalopathy Due to Pyruvate Carboxylase Deficiency 50 25 56
Leigh Syndrome Due to Pyruvate Carboxylase Deficiency 50 25 56
Pc Deficiency 50 25 71
Pyruvate Carboxylase Deficiency, Severe Neonatal Type 56
Pyruvate Carboxylase Deficiency, Infantile Form 56
Pyruvate Carboxylase Deficiency, Benign Type 56
Pyruvate Carboxylase Deficiency Type C 56
Pyruvate Carboxylase Deficiency Type a 56
Pyruvate Carboxylase Deficiency Type B 56
Ataxia with Lactic Acidosis, Type Ii 25
Type Ii Ataxia with Lactic Acidosis 25
Ataxia with Lactic Acidosis Type Ii 56
Leigh Syndrome Due to Pc Deficiency 56
Ataxia with Lactic Acidosis Type 2 56
Deficiency of Pyruvic Carboxylase 12
Ataxia with Lactic Acidosis 2 50
Pyruvate Carboxylase 13

Characteristics:

Orphanet epidemiological data:

56
pyruvate carboxylase deficiency
Inheritance: Autosomal recessive,Not applicable; Prevalence: 1-9/1000000 (Europe); Age of onset: Infancy,Neonatal; Age of death: early childhood;
pyruvate carboxylase deficiency, benign type
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy;
pyruvate carboxylase deficiency, infantile form
Inheritance: Autosomal recessive; Age of onset: Infancy; Age of death: early childhood,infantile;
pyruvate carboxylase deficiency, severe neonatal type
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal; Age of death: early childhood;

OMIM:

54
Inheritance:
autosomal recessive

Miscellaneous:
onset at birth or in early infancy
some patients may respond to thiamine treatment
can be categorized into 3 groups
group a, found in north american indians, has lactic acidosis and psychomotor retardation
group a patients die in the first years of life
group b, found in france and united kingdom, severe phenotype
group b patients die by 3 months of age
group c is relatively benign


HPO:

32
pyruvate carboxylase deficiency:
Onset and clinical course congenital onset
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 56  
Inborn errors of metabolism


Summaries for Pyruvate Carboxylase Deficiency

NIH Rare Diseases : 50 pyruvate carboxylase deficiency is an inherited disorder that causes lactic acid and other potentially toxic compounds to accumulate in the blood. high levels of these substances can damage the body's organs and tissues, particularly in the nervous system. researchers have identified at least three types of pyruvate carboxylase deficiency, types a, b, and c, which are distinguished by the severity of their signs and symptoms. this condition is caused by mutations in the pc gene and inherited in an autosomal recessive pattern. last updated: 6/1/2015

MalaCards based summary : Pyruvate Carboxylase Deficiency, also known as pyruvate carboxylase deficiency disease, is related to thrombophilia due to protein c deficiency, autosomal recessive and protein c deficiency, and has symptoms including hepatomegaly, seizures and global developmental delay. An important gene associated with Pyruvate Carboxylase Deficiency is PC (Pyruvate Carboxylase). The drug pyruvate has been mentioned in the context of this disorder. Affiliated tissues include cortex, liver and brain.

UniProtKB/Swiss-Prot : 71 Pyruvate carboxylase deficiency: Leads to lactic acidosis, mental retardation and death. It occurs in three forms: mild or type A, severe neonatal or type B, and a very mild lacticacidemia.

Genetics Home Reference : 25 Pyruvate carboxylase deficiency is an inherited disorder that causes lactic acid and other potentially toxic compounds to accumulate in the blood. High levels of these substances can damage the body's organs and tissues, particularly in the nervous system.

Wikipedia : 72 Pyruvate carboxylase deficiency is an inherited disorder that causes lactic acid and other potentially... more...

Description from OMIM: 266150
GeneReviews: NBK6852

Related Diseases for Pyruvate Carboxylase Deficiency

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

(show all 14)
id Related Disease Score Top Affiliating Genes
1 thrombophilia due to protein c deficiency, autosomal recessive 11.0
2 protein c deficiency 10.8
3 pancreatitis 10.0
4 insulinoma 10.0
5 hepatitis 9.9
6 hyperammonemia 9.9
7 cystinuria 9.9
8 citrullinemia 9.9
9 renal tubular acidosis 9.9
10 apraxia 9.9
11 ischemia 9.9
12 lactic acidosis 9.9
13 lung cancer 9.8
14 friedreich ataxia 9.8

Graphical network of the top 20 diseases related to Pyruvate Carboxylase Deficiency:



Diseases related to Pyruvate Carboxylase Deficiency

Symptoms & Phenotypes for Pyruvate Carboxylase Deficiency

Symptoms via clinical synopsis from OMIM:

54

Neurologic- Central Nervous System:
hypotonia
mental retardation
developmental delay
seizures
clonus
more
Metabolic Features:
lactic acidosis

Genitourinary- Kidneys:
renal tubular acidosis, proximal

Abdomen- Liver:
hepatomegaly

Laboratory- Abnormalities:
increased serum lactate
hypoglycemia
increased serum alanine
increased serum pyruvate
decreased pyruvate carboxylase (pc) activity (less than 5%)
more

Clinical features from OMIM:

266150

Human phenotypes related to Pyruvate Carboxylase Deficiency:

32 (show all 14)
id Description HPO Frequency HPO Source Accession
1 hepatomegaly 32 HP:0002240
2 seizures 32 HP:0001250
3 global developmental delay 32 HP:0001263
4 lactic acidosis 32 HP:0003128
5 increased serum lactate 32 HP:0002151
6 intellectual disability 32 HP:0001249
7 clonus 32 HP:0002169
8 hypoglycemia 32 HP:0001943
9 muscular hypotonia 32 HP:0001252
10 proximal renal tubular acidosis 32 HP:0002049
11 periventricular leukomalacia 32 HP:0006970
12 increased serum pyruvate 32 HP:0003542
13 neuronal loss in the cerebral cortex 32 HP:0007190
14 hyperalaninemia 32 HP:0003348

UMLS symptoms related to Pyruvate Carboxylase Deficiency:


clonus, seizures

Drugs & Therapeutics for Pyruvate Carboxylase Deficiency

Drugs for Pyruvate Carboxylase Deficiency (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


id Name Status Phase Clinical Trials Cas Number PubChem Id
1 pyruvate Nutraceutical

Interventional clinical trials:


id Name Status NCT ID Phase Drugs
1 Compassionate Use of Triheptanoin (C7) for Inherited Disorders of Energy Metabolism Available NCT01461304 triheptanoin

Search NIH Clinical Center for Pyruvate Carboxylase Deficiency

Cochrane evidence based reviews: pyruvate carboxylase deficiency disease

Genetic Tests for Pyruvate Carboxylase Deficiency

Genetic tests related to Pyruvate Carboxylase Deficiency:

id Genetic test Affiliating Genes
1 Pyruvate Carboxylase Deficiency 29 24 PC

Anatomical Context for Pyruvate Carboxylase Deficiency

MalaCards organs/tissues related to Pyruvate Carboxylase Deficiency:

39
Cortex, Liver, Brain

Publications for Pyruvate Carboxylase Deficiency

Articles related to Pyruvate Carboxylase Deficiency:

(show all 30)
id Title Authors Year
1
Pyruvate Carboxylase Deficiency Mimicking Diabetic Ketoacidosis. ( 28831725 )
2017
2
Pyruvate carboxylase deficiency: An underestimated cause of lactic acidosis. ( 28649521 )
2015
3
Unsuccessful treatment of severe pyruvate carboxylase deficiency with triheptanoin. ( 24114256 )
2014
4
Novel Mutations in the PC Gene in Patients with Type B Pyruvate Carboxylase Deficiency. ( 23430542 )
2013
5
A Patient With Pyruvate Carboxylase Deficiency and Nemaline Rods on Muscle Biopsy. ( 22965558 )
2013
6
Infantile parkinsonism and GABAergic hypotransmission in a patient with pyruvate carboxylase deficiency. ( 23973720 )
2013
7
Pyruvate carboxylase deficiency: mechanisms, mimics and anaplerosis. ( 20598931 )
2010
8
Structural insights on pathogenic effects of novel mutations causing pyruvate carboxylase deficiency. ( 19306334 )
2009
9
The molecular basis of pyruvate carboxylase deficiency: mosaicism correlates with prolonged survival. ( 18676167 )
2008
10
Pyruvate carboxylase deficiency: metabolic characteristics and new neurological aspects. ( 16278852 )
2006
11
A case of pyruvate carboxylase deficiency with atypical clinical and neuroradiological presentation. ( 16325442 )
2006
12
Pyruvate carboxylase deficiency: clinical and biochemical response to anaplerotic diet therapy. ( 15781190 )
2005
13
Intron retention and frameshift mutations result in severe pyruvate carboxylase deficiency in two male siblings. ( 12112657 )
2002
14
Pyruvate carboxylase deficiency--insights from liver transplantation. ( 12359142 )
2002
15
Pyruvate carboxylase deficiency. Report of a case and additional evidence for the "mild" phenotype. ( 11583052 )
2001
16
[Pyruvate carboxylase deficiency]. ( 11596335 )
2001
17
Pyruvate carboxylase deficiency: prenatal onset of ischemia-like brain lesions in two sibs with the acute neonatal form. ( 10323732 )
1999
18
Treatment of pyruvate carboxylase deficiency with high doses of citrate and aspartate. ( 10588840 )
1999
19
Molecular characterization of pyruvate carboxylase deficiency in two consanguineous families. ( 9585002 )
1998
20
Prenatal diagnosis of pyruvate carboxylase deficiency by direct measurement of catalytic activity on chorionic villi samples. ( 9826895 )
1998
21
Amerindian pyruvate carboxylase deficiency is associated with two distinct missense mutations. ( 9585612 )
1998
22
[Pyruvate carboxylase deficiency]. ( 9590065 )
1998
23
A case of benign pyruvate carboxylase deficiency with normal development. ( 9266366 )
1997
24
An atypical French form of pyruvate carboxylase deficiency. ( 7503391 )
1995
25
Prolonged survival in pyruvate carboxylase deficiency: lack of correlation with enzyme activity in cultured fibroblasts. ( 7720232 )
1995
26
MRI, clinical, and biochemical features of partial pyruvate carboxylase deficiency. ( 7822739 )
1994
27
Pyruvate Carboxylase Deficiency ( 20301764 )
1993
28
Pyruvate carboxylase deficiency: a benign variant with normal development. ( 1909777 )
1991
29
Neonatal pyruvate carboxylase deficiency with renal tubular acidosis and cystinuria. ( 6422151 )
1983
30
Secondary citrullinemia with hyperammonemia in four neonatal cases of pyruvate carboxylase deficiency. ( 6798542 )
1981

Variations for Pyruvate Carboxylase Deficiency

UniProtKB/Swiss-Prot genetic disease variations for Pyruvate Carboxylase Deficiency:

71
id Symbol AA change Variation ID SNP ID
1 PC p.Ala610Thr VAR_008095 rs28940589
2 PC p.Met743Ile VAR_008096 rs28940590
3 PC p.Val145Ala VAR_015199 rs28940591
4 PC p.Arg451Cys VAR_015200 rs113994143
5 PC p.Arg156Gln VAR_058957 rs119103241
6 PC p.Arg270Trp VAR_058958
7 PC p.Tyr304Cys VAR_058959
8 PC p.Arg583Leu VAR_058960 rs119103242
9 PC p.Arg631Gln VAR_058961 rs113994145

ClinVar genetic disease variations for Pyruvate Carboxylase Deficiency:

6 (show all 17)
id Gene Variation Type Significance SNP ID Assembly Location
1 PC NM_000920.3(PC): c.1828G> A (p.Ala610Thr) single nucleotide variant Pathogenic rs28940589 GRCh37 Chromosome 11, 66619415: 66619415
2 PC NM_000920.3(PC): c.2229G> T (p.Met743Ile) single nucleotide variant Pathogenic rs28940590 GRCh37 Chromosome 11, 66618389: 66618389
3 PC NM_000920.3(PC): c.434T> C (p.Val145Ala) single nucleotide variant Pathogenic rs28940591 GRCh37 Chromosome 11, 66638839: 66638839
4 PC NM_000920.3(PC): c.1351C> T (p.Arg451Cys) single nucleotide variant Pathogenic rs113994143 GRCh37 Chromosome 11, 66631262: 66631262
5 PC PC, IVS15, 4-BP DEL, TAGG, +2-5 deletion Pathogenic
6 PC PC, 2-BP DEL, 2491GT deletion Pathogenic
7 PC NM_001040716.1(PC): c.467G> A (p.Arg156Gln) single nucleotide variant Pathogenic rs119103241 GRCh37 Chromosome 11, 66638806: 66638806
8 PC NM_001040716.1(PC): c.1748G> T (p.Arg583Leu) single nucleotide variant Pathogenic rs119103242 GRCh37 Chromosome 11, 66619987: 66619987
9 PC PC, 1-BP DUP, 2876T duplication Pathogenic
10 PC NM_000920.3(PC): c.1705A> G (p.Thr569Ala) single nucleotide variant Pathogenic rs113994144 GRCh37 Chromosome 11, 66620030: 66620030
11 PC NM_000920.3(PC): c.184C> T (p.Arg62Cys) single nucleotide variant Pathogenic rs113994141 GRCh37 Chromosome 11, 66639295: 66639295
12 PC NM_000920.3(PC): c.1892G> A (p.Arg631Gln) single nucleotide variant Pathogenic rs113994145 GRCh37 Chromosome 11, 66619351: 66619351
13 PC NM_000920.3(PC): c.2114C> A (p.Ser705Ter) single nucleotide variant Pathogenic rs113994146 GRCh37 Chromosome 11, 66618620: 66618620
14 PC NM_000920.3(PC): c.2540C> T (p.Ala847Val) single nucleotide variant Pathogenic rs113994147 GRCh37 Chromosome 11, 66617869: 66617869
15 PC NM_000920.3(PC): c.3409_3410delCT (p.Leu1137Valfs) deletion Pathogenic rs113994148 GRCh37 Chromosome 11, 66616497: 66616498
16 PC NM_000920.3(PC): c.796T> A (p.Ser266Thr) single nucleotide variant Pathogenic rs113994142 GRCh37 Chromosome 11, 66637880: 66637880
17 PC NM_000920.3(PC): c.1357C> T (p.Arg453Ter) single nucleotide variant Pathogenic rs768514713 GRCh37 Chromosome 11, 66631256: 66631256

Expression for Pyruvate Carboxylase Deficiency

Search GEO for disease gene expression data for Pyruvate Carboxylase Deficiency.

Pathways for Pyruvate Carboxylase Deficiency

GO Terms for Pyruvate Carboxylase Deficiency

Sources for Pyruvate Carboxylase Deficiency

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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