MCID: PYR037
MIFTS: 38

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 53 72 23 49 24 55 71 36 28 13
Pyruvate Carboxylase Deficiency Disease 12 24 41 14 69
Leigh Necrotizing Encephalopathy Due to Pyruvate Carboxylase Deficiency 53 49 24 55
Leigh Syndrome Due to Pyruvate Carboxylase Deficiency 53 49 24 55
Pc Deficiency 53 49 24 71
Pyruvate Carboxylase Deficiency, Severe Neonatal Type 55
Pyruvate Carboxylase Deficiency, Infantile Form 55
Pyruvate Carboxylase Deficiency, Benign Type 55
Pyruvate Carboxylase Deficiency Type C 55
Pyruvate Carboxylase Deficiency Type a 55
Pyruvate Carboxylase Deficiency Type B 55
Ataxia with Lactic Acidosis, Type Ii 24
Type Ii Ataxia with Lactic Acidosis 24
Ataxia with Lactic Acidosis Type Ii 55
Leigh Syndrome Due to Pc Deficiency 55
Ataxia with Lactic Acidosis Type 2 55
Deficiency of Pyruvic Carboxylase 12
Ataxia with Lactic Acidosis Ii 53
Ataxia with Lactic Acidosis 2 49
Pyruvate Carboxylase 13

Characteristics:

Orphanet epidemiological data:

55
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:

53
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:

31
pyruvate carboxylase deficiency:
Onset and clinical course congenital onset
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 55  
Inborn errors of metabolism


External Ids:

OMIM 53 266150
Disease Ontology 12 DOID:3651
ICD10 32 E74.4
MeSH 41 D015324
NCIt 46 C85040
SNOMED-CT 64 124716008 87694001
ICD10 via Orphanet 33 E74.4
MESH via Orphanet 42 D015324
UMLS via Orphanet 70 C0034341 C2931141
KEGG 36 H00073
UMLS 69 C0034341

Summaries for Pyruvate Carboxylase Deficiency

NIH Rare Diseases : 49 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 seizures, clonus and intellectual disability. An important gene associated with Pyruvate Carboxylase Deficiency is PC (Pyruvate Carboxylase), and among its related pathways/superpathways are Pyruvate metabolism and Citrate cycle (TCA cycle). The drug pyruvate has been mentioned in the context of this disorder. Affiliated tissues include cortex, brain and liver.

Genetics Home Reference : 24 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.

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.

Wikipedia : 72 Pyruvate carboxylase deficiency is an inherited disorder that causes lactic acid and to accumulate in... 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 19)
# Related Disease Score Top Affiliating Genes
1 thrombophilia due to protein c deficiency, autosomal recessive 11.2
2 protein c deficiency 11.1
3 insulinoma 10.1
4 pancreatitis 10.1
5 hepatitis 10.0
6 citrullinemia, classic 9.9
7 cystinuria 9.9
8 diabetes mellitus, ketosis-prone 9.9
9 carbonic anhydrase va deficiency, hyperammonemia due to 9.9
10 renal tubular acidosis 9.9
11 ischemia 9.9
12 lactic acidosis 9.9
13 ocular motor apraxia 9.9
14 apraxia 9.9
15 lung cancer 9.9
16 hepatitis c virus 9.9
17 hepatitis c 9.9
18 adenocarcinoma 9.9
19 gallbladder cancer 9.9

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:

53
Neurologic Central Nervous System:
seizures
clonus
periventricular leukomalacia
neuronal loss in the cerebral cortex
developmental delay
more
Laboratory Abnormalities:
hypoglycemia
increased serum lactate
increased serum pyruvate
increased serum alanine
decreased pyruvate carboxylase (pc) activity (less than 5%)
more
Genitourinary Kidneys:
renal tubular acidosis, proximal

Abdomen Liver:
hepatomegaly

Metabolic Features:
lactic acidosis


Clinical features from OMIM:

266150

Human phenotypes related to Pyruvate Carboxylase Deficiency:

31 (show all 14)
# Description HPO Frequency HPO Source Accession
1 seizures 31 HP:0001250
2 clonus 31 HP:0002169
3 intellectual disability 31 HP:0001249
4 global developmental delay 31 HP:0001263
5 hepatomegaly 31 HP:0002240
6 hypoglycemia 31 HP:0001943
7 increased serum lactate 31 HP:0002151
8 lactic acidosis 31 HP:0003128
9 proximal renal tubular acidosis 31 HP:0002049
10 increased serum pyruvate 31 HP:0003542
11 generalized hypotonia 31 HP:0001290
12 hyperalaninemia 31 HP:0003348
13 periventricular leukomalacia 31 HP:0006970
14 neuronal loss in the cerebral cortex 31 HP:0007190

UMLS symptoms related to Pyruvate Carboxylase Deficiency:


seizures, clonus

Drugs & Therapeutics for Pyruvate Carboxylase Deficiency

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


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

Interventional clinical trials:


# 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:

# Genetic test Affiliating Genes
1 Pyruvate Carboxylase Deficiency 28 PC

Anatomical Context for Pyruvate Carboxylase Deficiency

MalaCards organs/tissues related to Pyruvate Carboxylase Deficiency:

38
Cortex, Brain, Liver

Publications for Pyruvate Carboxylase Deficiency

Articles related to Pyruvate Carboxylase Deficiency:

(show all 30)
# 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
A Patient With Pyruvate Carboxylase Deficiency and Nemaline Rods on Muscle Biopsy. ( 22965558 )
2013
5
Novel Mutations in the PC Gene in Patients with Type B Pyruvate Carboxylase Deficiency. ( 23430542 )
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]. ( 11596335 )
2001
16
Pyruvate carboxylase deficiency. Report of a case and additional evidence for the "mild" phenotype. ( 11583052 )
2001
17
Treatment of pyruvate carboxylase deficiency with high doses of citrate and aspartate. ( 10588840 )
1999
18
Pyruvate carboxylase deficiency: prenatal onset of ischemia-like brain lesions in two sibs with the acute neonatal form. ( 10323732 )
1999
19
Prenatal diagnosis of pyruvate carboxylase deficiency by direct measurement of catalytic activity on chorionic villi samples. ( 9826895 )
1998
20
Molecular characterization of pyruvate carboxylase deficiency in two consanguineous families. ( 9585002 )
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
Prolonged survival in pyruvate carboxylase deficiency: lack of correlation with enzyme activity in cultured fibroblasts. ( 7720232 )
1995
25
An atypical French form of pyruvate carboxylase deficiency. ( 7503391 )
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
# 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 19)
# Gene Variation Type Significance SNP ID Assembly Location
1 PC NM_000920.3(PC): c.1705A> G (p.Thr569Ala) single nucleotide variant Pathogenic rs113994144 GRCh37 Chromosome 11, 66620030: 66620030
2 PC NM_000920.3(PC): c.184C> T (p.Arg62Cys) single nucleotide variant Pathogenic rs113994141 GRCh37 Chromosome 11, 66639295: 66639295
3 PC NM_000920.3(PC): c.1892G> A (p.Arg631Gln) single nucleotide variant Pathogenic rs113994145 GRCh37 Chromosome 11, 66619351: 66619351
4 PC NM_000920.3(PC): c.2114C> A (p.Ser705Ter) single nucleotide variant Pathogenic rs113994146 GRCh37 Chromosome 11, 66618620: 66618620
5 PC NM_000920.3(PC): c.2540C> T (p.Ala847Val) single nucleotide variant Pathogenic rs113994147 GRCh37 Chromosome 11, 66617869: 66617869
6 PC NM_000920.3(PC): c.3409_3410delCT (p.Leu1137Valfs) deletion Pathogenic rs113994148 GRCh37 Chromosome 11, 66616497: 66616498
7 PC NM_000920.3(PC): c.796T> A (p.Ser266Thr) single nucleotide variant Pathogenic rs113994142 GRCh37 Chromosome 11, 66637880: 66637880
8 PC NM_000920.3(PC): c.1828G> A (p.Ala610Thr) single nucleotide variant Pathogenic rs28940589 GRCh37 Chromosome 11, 66619415: 66619415
9 PC NM_000920.3(PC): c.2229G> T (p.Met743Ile) single nucleotide variant Pathogenic rs28940590 GRCh37 Chromosome 11, 66618389: 66618389
10 PC NM_000920.3(PC): c.434T> C (p.Val145Ala) single nucleotide variant Pathogenic rs28940591 GRCh37 Chromosome 11, 66638839: 66638839
11 PC NM_000920.3(PC): c.1351C> T (p.Arg451Cys) single nucleotide variant Pathogenic rs113994143 GRCh37 Chromosome 11, 66631262: 66631262
12 PC PC, IVS15, 4-BP DEL, TAGG, +2-5 deletion Pathogenic
13 PC PC, 2-BP DEL, 2491GT deletion Pathogenic
14 PC NM_001040716.1(PC): c.467G> A (p.Arg156Gln) single nucleotide variant Pathogenic rs119103241 GRCh37 Chromosome 11, 66638806: 66638806
15 PC NM_001040716.1(PC): c.1748G> T (p.Arg583Leu) single nucleotide variant Pathogenic rs119103242 GRCh37 Chromosome 11, 66619987: 66619987
16 PC PC, 1-BP DUP, 2876T duplication Pathogenic
17 PC NM_000920.3(PC): c.1357C> T (p.Arg453Ter) single nucleotide variant Pathogenic rs768514713 GRCh38 Chromosome 11, 66863785: 66863785
18 PC NM_000920.3(PC): c.1368+1G> A single nucleotide variant Likely pathogenic rs755640269 GRCh38 Chromosome 11, 66863773: 66863773
19 PC NM_000920.3(PC): c.2668G> T (p.Val890Phe) single nucleotide variant Pathogenic GRCh38 Chromosome 11, 66850270: 66850270

Expression for Pyruvate Carboxylase Deficiency

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

Pathways for Pyruvate Carboxylase Deficiency

Pathways related to Pyruvate Carboxylase Deficiency according to KEGG:

36
# Name Kegg Source Accession
1 Pyruvate metabolism hsa00620
2 Citrate cycle (TCA cycle) hsa00020

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
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 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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