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 57 76 24 53 25 59 75 37 29 13 6 40
Pyruvate Carboxylase Deficiency Disease 12 25 44 15 73
Leigh Necrotizing Encephalopathy Due to Pyruvate Carboxylase Deficiency 57 53 25 59
Leigh Syndrome Due to Pyruvate Carboxylase Deficiency 57 53 25 59
Pc Deficiency 57 53 25 75
Pyruvate Carboxylase Deficiency, Severe Neonatal Type 59
Pyruvate Carboxylase Deficiency, Infantile Type 59
Pyruvate Carboxylase Deficiency, Benign Type 59
Pyruvate Carboxylase Deficiency Type C 59
Pyruvate Carboxylase Deficiency Type a 59
Pyruvate Carboxylase Deficiency Type B 59
Ataxia with Lactic Acidosis, Type Ii 25
Type Ii Ataxia with Lactic Acidosis 25
Ataxia with Lactic Acidosis Type Ii 59
Leigh Syndrome Due to Pc Deficiency 59
Ataxia with Lactic Acidosis Type 2 59
Deficiency of Pyruvic Carboxylase 12
Ataxia with Lactic Acidosis Ii 57
Ataxia with Lactic Acidosis 2 53
Pyruvate Carboxylase 13

Characteristics:

Orphanet epidemiological data:

59
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 type
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:

57
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: 59  
Inborn errors of metabolism


External Ids:

OMIM 57 266150
Disease Ontology 12 DOID:3651
ICD10 33 E74.4
MeSH 44 D015324
NCIt 50 C85040
SNOMED-CT 68 124716008 87694001
ICD10 via Orphanet 34 E74.4
MESH via Orphanet 45 D015324
UMLS via Orphanet 74 C0034341 C2931141
KEGG 37 H00073
UMLS 73 C0034341

Summaries for Pyruvate Carboxylase Deficiency

NIH Rare Diseases : 53 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.

MalaCards based summary : Pyruvate Carboxylase Deficiency, also known as pyruvate carboxylase deficiency disease, is related to propionic acidemia and thrombophilia due to protein c deficiency, autosomal recessive, and has symptoms including clonus and seizures. 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, liver and brain, and related phenotypes are intellectual disability and seizures

UniProtKB/Swiss-Prot : 75 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 : 76 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 12)
# Related Disease Score Top Affiliating Genes
1 propionic acidemia 11.3
2 thrombophilia due to protein c deficiency, autosomal recessive 11.2
3 leigh syndrome, french canadian type 11.2
4 hyperornithinemia-hyperammonemia-homocitrullinuria syndrome 11.2
5 protein c deficiency 11.1
6 lactic acidosis 10.1
7 cystinuria 9.9
8 diabetes mellitus, ketosis-prone 9.9
9 renal tubular acidosis 9.9
10 ischemia 9.9
11 ocular motor apraxia 9.9
12 apraxia 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:

57
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:

32 (show all 15)
# Description HPO Frequency HPO Source Accession
1 intellectual disability 32 HP:0001249
2 seizures 32 HP:0001250
3 muscular hypotonia 32 HP:0001252
4 global developmental delay 32 HP:0001263
5 generalized hypotonia 32 HP:0001290
6 hypoglycemia 32 HP:0001943
7 proximal renal tubular acidosis 32 HP:0002049
8 increased serum lactate 32 HP:0002151
9 clonus 32 HP:0002169
10 hepatomegaly 32 HP:0002240
11 lactic acidosis 32 HP:0003128
12 hyperalaninemia 32 HP:0003348
13 increased serum pyruvate 32 HP:0003542
14 periventricular leukomalacia 32 HP:0006970
15 neuronal loss in the cerebral cortex 32 HP:0007190

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):


# 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 29 PC

Anatomical Context for Pyruvate Carboxylase Deficiency

MalaCards organs/tissues related to Pyruvate Carboxylase Deficiency:

41
Cortex, Liver, Brain

Publications for Pyruvate Carboxylase Deficiency

Articles related to Pyruvate Carboxylase Deficiency:

(show all 32)
# Title Authors Year
1
Prenatal sonographic description of fetuses affected by pyruvate dehydrogenase or pyruvate carboxylase deficiency. ( 29752808 )
2018
2
Pyruvate Carboxylase Deficiency Mimicking Diabetic Ketoacidosis. ( 28831725 )
2017
3
Pyruvate carboxylase deficiency: An underestimated cause of lactic acidosis. ( 28649521 )
2015
4
Unsuccessful treatment of severe pyruvate carboxylase deficiency with triheptanoin. ( 24114256 )
2014
5
Novel Mutations in the PC Gene in Patients with Type B Pyruvate Carboxylase Deficiency. ( 23430542 )
2013
6
A Patient With Pyruvate Carboxylase Deficiency and Nemaline Rods on Muscle Biopsy. ( 22965558 )
2013
7
Infantile parkinsonism and GABAergic hypotransmission in a patient with pyruvate carboxylase deficiency. ( 23973720 )
2013
8
Pyruvate carboxylase deficiency: mechanisms, mimics and anaplerosis. ( 20598931 )
2010
9
Structural insights on pathogenic effects of novel mutations causing pyruvate carboxylase deficiency. ( 19306334 )
2009
10
The molecular basis of pyruvate carboxylase deficiency: mosaicism correlates with prolonged survival. ( 18676167 )
2008
11
A case of pyruvate carboxylase deficiency with atypical clinical and neuroradiological presentation. ( 16325442 )
2006
12
Pyruvate carboxylase deficiency: metabolic characteristics and new neurological aspects. ( 16278852 )
2006
13
Pyruvate carboxylase deficiency: clinical and biochemical response to anaplerotic diet therapy. ( 15781190 )
2005
14
Intron retention and frameshift mutations result in severe pyruvate carboxylase deficiency in two male siblings. ( 12112657 )
2002
15
Pyruvate carboxylase deficiency--insights from liver transplantation. ( 12359142 )
2002
16
[Pyruvate carboxylase deficiency]. ( 11596335 )
2001
17
Pyruvate carboxylase deficiency. Report of a case and additional evidence for the &amp;quot;mild&amp;quot; phenotype. ( 11583052 )
2001
18
Treatment of pyruvate carboxylase deficiency with high doses of citrate and aspartate. ( 10588840 )
1999
19
Pyruvate carboxylase deficiency: prenatal onset of ischemia-like brain lesions in two sibs with the acute neonatal form. ( 10323732 )
1999
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
Prenatal diagnosis of pyruvate carboxylase deficiency by direct measurement of catalytic activity on chorionic villi samples. ( 9826895 )
1998
23
[Pyruvate carboxylase deficiency]. ( 9590065 )
1998
24
A case of benign pyruvate carboxylase deficiency with normal development. ( 9266366 )
1997
25
Prolonged survival in pyruvate carboxylase deficiency: lack of correlation with enzyme activity in cultured fibroblasts. ( 7720232 )
1995
26
An atypical French form of pyruvate carboxylase deficiency. ( 7503391 )
1995
27
MRI, clinical, and biochemical features of partial pyruvate carboxylase deficiency. ( 7822739 )
1994
28
Pyruvate Carboxylase Deficiency ( 20301764 )
1993
29
Pyruvate carboxylase deficiency: a benign variant with normal development. ( 1909777 )
1991
30
Neonatal pyruvate carboxylase deficiency with renal tubular acidosis and cystinuria. ( 6422151 )
1983
31
Secondary citrullinemia with hyperammonemia in four neonatal cases of pyruvate carboxylase deficiency. ( 6798542 )
1981
32
Hyperalaninemia hyperpyruvicemia and lactic acidosis due to pyruvate carboxylase deficiency of the liver; treatment with thiamine and lipoic acid. ( 817914 )
1976

Variations for Pyruvate Carboxylase Deficiency

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

75
# 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 top 50) (show all 113)
# 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.1828G> A (p.Ala610Thr) single nucleotide variant Pathogenic rs28940589 GRCh38 Chromosome 11, 66851944: 66851944
3 PC NM_000920.3(PC): c.2229G> T (p.Met743Ile) single nucleotide variant Pathogenic rs28940590 GRCh37 Chromosome 11, 66618389: 66618389
4 PC NM_000920.3(PC): c.2229G> T (p.Met743Ile) single nucleotide variant Pathogenic rs28940590 GRCh38 Chromosome 11, 66850918: 66850918
5 PC NM_000920.3(PC): c.434T> C (p.Val145Ala) single nucleotide variant Pathogenic rs28940591 GRCh37 Chromosome 11, 66638839: 66638839
6 PC NM_000920.3(PC): c.434T> C (p.Val145Ala) single nucleotide variant Pathogenic rs28940591 GRCh38 Chromosome 11, 66871368: 66871368
7 PC NM_000920.3(PC): c.1351C> T (p.Arg451Cys) single nucleotide variant Pathogenic rs113994143 GRCh37 Chromosome 11, 66631262: 66631262
8 PC NM_000920.3(PC): c.1351C> T (p.Arg451Cys) single nucleotide variant Pathogenic rs113994143 GRCh38 Chromosome 11, 66863791: 66863791
9 PC PC, IVS15, 4-BP DEL, TAGG, +2-5 deletion Pathogenic
10 PC PC, 2-BP DEL, 2491GT deletion Pathogenic
11 PC NM_001040716.1(PC): c.467G> A (p.Arg156Gln) single nucleotide variant Pathogenic rs119103241 GRCh37 Chromosome 11, 66638806: 66638806
12 PC NM_001040716.1(PC): c.467G> A (p.Arg156Gln) single nucleotide variant Pathogenic rs119103241 GRCh38 Chromosome 11, 66871335: 66871335
13 PC NM_001040716.1(PC): c.1748G> T (p.Arg583Leu) single nucleotide variant Pathogenic rs119103242 GRCh37 Chromosome 11, 66619987: 66619987
14 PC NM_001040716.1(PC): c.1748G> T (p.Arg583Leu) single nucleotide variant Pathogenic rs119103242 GRCh38 Chromosome 11, 66852516: 66852516
15 PC PC, 1-BP DUP, 2876T duplication Pathogenic
16 PC NM_000920.3(PC): c.796T> A (p.Ser266Thr) single nucleotide variant Pathogenic rs113994142 GRCh38 Chromosome 11, 66870409: 66870409
17 PC NM_000920.3(PC): c.3409_3410delCT (p.Leu1137Valfs) deletion Pathogenic rs113994148 GRCh37 Chromosome 11, 66616497: 66616498
18 PC NM_000920.3(PC): c.3409_3410delCT (p.Leu1137Valfs) deletion Pathogenic rs113994148 GRCh38 Chromosome 11, 66849026: 66849027
19 PC NM_000920.3(PC): c.796T> A (p.Ser266Thr) single nucleotide variant Pathogenic rs113994142 GRCh37 Chromosome 11, 66637880: 66637880
20 PC NM_000920.3(PC): c.1705A> G (p.Thr569Ala) single nucleotide variant Pathogenic rs113994144 GRCh37 Chromosome 11, 66620030: 66620030
21 PC NM_000920.3(PC): c.1705A> G (p.Thr569Ala) single nucleotide variant Pathogenic rs113994144 GRCh38 Chromosome 11, 66852559: 66852559
22 PC NM_000920.3(PC): c.184C> T (p.Arg62Cys) single nucleotide variant Pathogenic rs113994141 GRCh37 Chromosome 11, 66639295: 66639295
23 PC NM_000920.3(PC): c.184C> T (p.Arg62Cys) single nucleotide variant Pathogenic rs113994141 GRCh38 Chromosome 11, 66871824: 66871824
24 PC NM_000920.3(PC): c.1892G> A (p.Arg631Gln) single nucleotide variant Pathogenic rs113994145 GRCh37 Chromosome 11, 66619351: 66619351
25 PC NM_000920.3(PC): c.1892G> A (p.Arg631Gln) single nucleotide variant Pathogenic rs113994145 GRCh38 Chromosome 11, 66851880: 66851880
26 PC NM_000920.3(PC): c.2114C> A (p.Ser705Ter) single nucleotide variant Pathogenic rs113994146 GRCh37 Chromosome 11, 66618620: 66618620
27 PC NM_000920.3(PC): c.2114C> A (p.Ser705Ter) single nucleotide variant Pathogenic rs113994146 GRCh38 Chromosome 11, 66851149: 66851149
28 PC NM_000920.3(PC): c.2540C> T (p.Ala847Val) single nucleotide variant Pathogenic rs113994147 GRCh37 Chromosome 11, 66617869: 66617869
29 PC NM_000920.3(PC): c.2540C> T (p.Ala847Val) single nucleotide variant Pathogenic rs113994147 GRCh38 Chromosome 11, 66850398: 66850398
30 PC NM_000920.3(PC): c.2804C> T (p.Ala935Val) single nucleotide variant Uncertain significance rs139540331 GRCh38 Chromosome 11, 66850031: 66850031
31 PC NM_000920.3(PC): c.2804C> T (p.Ala935Val) single nucleotide variant Uncertain significance rs139540331 GRCh37 Chromosome 11, 66617502: 66617502
32 PC NM_000920.3(PC): c.1608G> A (p.Pro536=) single nucleotide variant Conflicting interpretations of pathogenicity rs139074169 GRCh38 Chromosome 11, 66852656: 66852656
33 PC NM_000920.3(PC): c.1608G> A (p.Pro536=) single nucleotide variant Conflicting interpretations of pathogenicity rs139074169 GRCh37 Chromosome 11, 66620127: 66620127
34 PC NM_000920.3(PC): c.1513+13delA deletion Conflicting interpretations of pathogenicity rs755170894 GRCh38 Chromosome 11, 66853226: 66853226
35 PC NM_000920.3(PC): c.1513+13delA deletion Conflicting interpretations of pathogenicity rs755170894 GRCh37 Chromosome 11, 66620697: 66620697
36 PC NM_000920.3(PC): c.1344G> A (p.Ala448=) single nucleotide variant Conflicting interpretations of pathogenicity rs148281644 GRCh38 Chromosome 11, 66863798: 66863798
37 PC NM_000920.3(PC): c.1344G> A (p.Ala448=) single nucleotide variant Conflicting interpretations of pathogenicity rs148281644 GRCh37 Chromosome 11, 66631269: 66631269
38 PC NM_000920.3(PC): c.788G> A (p.Arg263Gln) single nucleotide variant Conflicting interpretations of pathogenicity rs769177104 GRCh37 Chromosome 11, 66637888: 66637888
39 PC NM_000920.3(PC): c.788G> A (p.Arg263Gln) single nucleotide variant Conflicting interpretations of pathogenicity rs769177104 GRCh38 Chromosome 11, 66870417: 66870417
40 PC NM_022172.2(PC): c.2095G> T (p.Val699Leu) single nucleotide variant no interpretation for the single variant rs760108147 GRCh37 Chromosome 11, 66618639: 66618639
41 PC NM_022172.2(PC): c.2095G> T (p.Val699Leu) single nucleotide variant no interpretation for the single variant rs760108147 GRCh38 Chromosome 11, 66851168: 66851168
42 PC NM_022172.2(PC): c.2095G> A (p.Val699Met) single nucleotide variant no interpretation for the single variant rs760108147 GRCh37 Chromosome 11, 66618639: 66618639
43 PC NM_022172.2(PC): c.2095G> A (p.Val699Met) single nucleotide variant no interpretation for the single variant rs760108147 GRCh38 Chromosome 11, 66851168: 66851168
44 PC NM_000920.3(PC): c.3473G> A (p.Arg1158His) single nucleotide variant Uncertain significance rs149054698 GRCh38 Chromosome 11, 66848963: 66848963
45 PC NM_000920.3(PC): c.3473G> A (p.Arg1158His) single nucleotide variant Uncertain significance rs149054698 GRCh37 Chromosome 11, 66616434: 66616434
46 PC NM_000920.3(PC): c.2292C> G (p.Pro764=) single nucleotide variant Uncertain significance rs757918962 GRCh37 Chromosome 11, 66618326: 66618326
47 PC NM_000920.3(PC): c.2292C> G (p.Pro764=) single nucleotide variant Uncertain significance rs757918962 GRCh38 Chromosome 11, 66850855: 66850855
48 PC NM_000920.3(PC): c.879C> T (p.Ser293=) single nucleotide variant Uncertain significance rs183131461 GRCh37 Chromosome 11, 66637797: 66637797
49 PC NM_000920.3(PC): c.879C> T (p.Ser293=) single nucleotide variant Uncertain significance rs183131461 GRCh38 Chromosome 11, 66870326: 66870326
50 PC NM_000920.3(PC): c.52C> A (p.Arg18=) single nucleotide variant Conflicting interpretations of pathogenicity rs144583275 GRCh37 Chromosome 11, 66639579: 66639579

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:

37
# 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
17 ExPASy
19 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 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
Content
Loading form....