MCD
MCID: MLT018
MIFTS: 45

Multiple Carboxylase Deficiency (MCD)

Categories: Metabolic diseases, Rare diseases, Skin diseases

Aliases & Classifications for Multiple Carboxylase Deficiency

MalaCards integrated aliases for Multiple Carboxylase Deficiency:

Name: Multiple Carboxylase Deficiency 12 20 58 54 44 15 70
Mcd 20 58
Holocarboxylase Synthetase Deficiency 70

Characteristics:

Orphanet epidemiological data:

58
multiple carboxylase deficiency
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal;

Classifications:

Orphanet: 58  
Rare skin diseases
Inborn errors of metabolism


External Ids:

Disease Ontology 12 DOID:857
MeSH 44 D009100
SNOMED-CT 67 62151000119109
ICD10 32 D81.81
MESH via Orphanet 45 D009100
ICD10 via Orphanet 33 E53.8
UMLS via Orphanet 71 C0026755
Orphanet 58 ORPHA148
UMLS 70 C0026755 C0268581

Summaries for Multiple Carboxylase Deficiency

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 148 Definition Multiple carboxylase deficiency (MCD) is a term used to describe inborn errors of biotin metabolism characterized by reduced activities of biotin-dependent enzymes resulting in a wide spectrum of symptoms, including feeding difficulty, breathing difficulties, lethargy, seizures, skin rash, alopecia, and developmental delay. Epidemiology The prevalence of MCD is unknown, but the condition is rare. There is no specific geographic or ethnic predominance. Clinical description There are two major clinical forms of MCD depending on their underlying cause: biotinidase deficiency (see this term) in which affected individuals typically develop symptoms of variable severity during the first few months of life, and holocarboxylase synthetase deficiency (see this term) in which affected individuals usually develop symptoms within hours, days or weeks of birth. Etiology Biotinidase deficiency is caused by mutations in the BTD gene (3p25) and holocarboxylase synthetase deficiency by mutations in the HLCS gene (21q22.1). Genetic counseling Both disorders are inherited as autosomal recessive traits.

MalaCards based summary : Multiple Carboxylase Deficiency, also known as mcd, is related to holocarboxylase synthetase deficiency and biotin deficiency, and has symptoms including seizures, vomiting and lethargy. An important gene associated with Multiple Carboxylase Deficiency is HLCS (Holocarboxylase Synthetase), and among its related pathways/superpathways are Metabolism and Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha). Affiliated tissues include spinal cord, eye and skin, and related phenotypes are hyperammonemia and organic aciduria

Disease Ontology : 12 An amino acid metabolic disorder that involves failures of carboxylation enzymes.

Wikipedia : 73 Multiple carboxylase deficiency is a form of metabolic disorder involving failures of carboxylation... more...

Related Diseases for Multiple Carboxylase Deficiency

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

(show top 50) (show all 122)
# Related Disease Score Top Affiliating Genes
1 holocarboxylase synthetase deficiency 32.7 SLC5A6 PNPO PC HLCS BTD
2 biotin deficiency 30.8 SLC5A6 PCCB PCCA PC MCCC1 HLCS
3 organic acidemia 30.5 PCCB PCCA HLCS BTD ACADM
4 biotinidase deficiency 29.8 VNN2 SLC5A6 PNPO PCCB PC MOCS1
5 abdominal obesity-metabolic syndrome 1 29.5 PCCA OTC HADHA BTD ACADM
6 3-methylcrotonyl-coa carboxylase deficiency 28.4 PCCB MCCC2 MCCC1 HLCS HADHA HADH
7 macular dystrophy, corneal 11.6
8 multicentric castleman disease 11.5
9 malonyl-coa decarboxylase deficiency 11.5
10 lipoid nephrosis 11.0
11 c1q nephropathy 11.0
12 kaposi sarcoma 10.9
13 corneal dystrophy, meesmann, 1 10.9
14 cortical malformations, occipital 10.9
15 focal segmental glomerulosclerosis 10 10.9
16 microlissencephaly 10.9
17 non-alcoholic fatty liver disease 10.5
18 non-alcoholic steatohepatitis 10.4
19 alopecia 10.4
20 fatty liver disease 10.3
21 metabolic acidosis 10.3
22 fatty liver disease, nonalcoholic 1 10.3
23 monocarboxylate transporter 1 deficiency 10.3 PC HLCS
24 exanthem 10.3
25 lactic acidosis 10.3
26 castleman disease 10.2
27 carbonic anhydrase va deficiency, hyperammonemia due to 10.2
28 hypotonia 10.2
29 fructose-1,6-bisphosphatase deficiency 10.2 PCCA PC
30 thiamine metabolism dysfunction syndrome 2 10.2 SLC5A6 BTD
31 metaphyseal chondrodysplasia, schmid type 10.1
32 focal segmental glomerulosclerosis 10.1
33 pyridoxamine 5-prime-phosphate oxidase deficiency 10.1 PNPO BTD
34 leigh syndrome 10.1
35 autosomal recessive disease 10.1
36 sarcoma 10.1
37 spindle cell sarcoma 10.1
38 pyrimidine metabolic disorder 10.1 OTC ADSL
39 nephrotic syndrome 10.0
40 glomerulonephritis 10.0
41 liver disease 10.0
42 cytokine deficiency 10.0
43 kshv inflammatory cytokine syndrome 10.0
44 lymphoma aids related 10.0
45 isovaleric acidemia 10.0 PCCB HADHA BTD
46 cerebral creatine deficiency syndrome 2 10.0 PNPO BTD ADSL
47 reye syndrome 10.0 OTC ACADM
48 ataxia and polyneuropathy, adult-onset 9.9
49 diabetes mellitus, ketosis-prone 9.9
50 psoriasis 14, pustular 9.9

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



Diseases related to Multiple Carboxylase Deficiency

Symptoms & Phenotypes for Multiple Carboxylase Deficiency

Human phenotypes related to Multiple Carboxylase Deficiency:

58 31 (show all 29)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hyperammonemia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001987
2 organic aciduria 58 31 hallmark (90%) Very frequent (99-80%) HP:0001992
3 metabolic ketoacidosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0005979
4 skin rash 58 31 frequent (33%) Frequent (79-30%) HP:0000988
5 feeding difficulties 58 31 frequent (33%) Frequent (79-30%) HP:0011968
6 psychomotor retardation 58 31 frequent (33%) Frequent (79-30%) HP:0025356
7 seizure 31 frequent (33%) HP:0001250
8 hypotonia 31 frequent (33%) HP:0001252
9 decreased biotinidase level 31 frequent (33%) HP:0410145
10 ataxia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001251
11 hearing impairment 58 31 occasional (7.5%) Occasional (29-5%) HP:0000365
12 alopecia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001596
13 lethargy 58 31 occasional (7.5%) Occasional (29-5%) HP:0001254
14 tachypnea 58 31 occasional (7.5%) Occasional (29-5%) HP:0002789
15 coma 58 31 occasional (7.5%) Occasional (29-5%) HP:0001259
16 respiratory distress 58 31 occasional (7.5%) Occasional (29-5%) HP:0002098
17 limb muscle weakness 58 31 occasional (7.5%) Occasional (29-5%) HP:0003690
18 optic atrophy 58 31 very rare (1%) Very rare (<4-1%) HP:0000648
19 scotoma 58 31 very rare (1%) Very rare (<4-1%) HP:0000575
20 spastic paraparesis 58 31 very rare (1%) Very rare (<4-1%) HP:0002313
21 spinal cord posterior columns myelin loss 58 31 very rare (1%) Very rare (<4-1%) HP:0008311
22 seizures 58 Frequent (79-30%)
23 muscular hypotonia 58 Frequent (79-30%)
24 visual impairment 58 Occasional (29-5%)
25 abnormality of the immune system 58 Occasional (29-5%)
26 abnormality of the eye 58 Occasional (29-5%)
27 abnormality of the nervous system 58 Very frequent (99-80%)
28 abnormal enzyme/coenzyme activity 58 Very frequent (99-80%)
29 decreased biotinidase activity 58 Frequent (79-30%)

UMLS symptoms related to Multiple Carboxylase Deficiency:


seizures; vomiting; lethargy; exanthema

GenomeRNAi Phenotypes related to Multiple Carboxylase Deficiency according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00240-S-1 9.62 ADSL
2 Decreased viability GR00249-S 9.62 ACADM HADH HLCS MCCC2 MOCS1 PCCB
3 Decreased viability GR00381-A-1 9.62 MOCS1 PCCB
4 Decreased viability GR00386-A-1 9.62 ACACA ACADM HADHA MCCC1 MOCS1 SLC5A6
5 Decreased viability GR00402-S-2 9.62 ACADM MT-ATP6 PC

MGI Mouse Phenotypes related to Multiple Carboxylase Deficiency:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 mortality/aging MP:0010768 9.73 ACACA ACADM ADSL HADHA HLCS MCCC1
2 renal/urinary system MP:0005367 9.17 BTD HADH HADHA OTC PCCA PCCB

Drugs & Therapeutics for Multiple Carboxylase Deficiency

Search Clinical Trials , NIH Clinical Center for Multiple Carboxylase Deficiency

Cochrane evidence based reviews: multiple carboxylase deficiency

Genetic Tests for Multiple Carboxylase Deficiency

Anatomical Context for Multiple Carboxylase Deficiency

MalaCards organs/tissues related to Multiple Carboxylase Deficiency:

40
Spinal Cord, Eye, Skin

Publications for Multiple Carboxylase Deficiency

Articles related to Multiple Carboxylase Deficiency:

(show top 50) (show all 196)
# Title Authors PMID Year
1
A case of holocarboxylase synthetase deficiency with insufficient response to prenatal biotin therapy. 61 54
19201116 2009
2
Impaired biotinidase activity disrupts holocarboxylase synthetase expression in late onset multiple carboxylase deficiency. 54 61
18845537 2008
3
Reduced half-life of holocarboxylase synthetase from patients with severe multiple carboxylase deficiency. 61 54
18429047 2008
4
Holocarboxylase synthetase deficiency: report of one case. 54 61
17407983 2006
5
Molecular genetics of biotin metabolism: old vitamin, new science. 61 54
15992684 2005
6
Paradoxical regulation of biotin utilization in brain and liver and implications for inherited multiple carboxylase deficiency. 54 61
15456772 2004
7
Biotin responsive multiple carboxylase deficiency presenting as diabetic ketoacidosis. 61 54
15095958 2004
8
Reduced histone biotinylation in multiple carboxylase deficiency patients: a nuclear role for holocarboxylase synthetase. 54 61
14613969 2004
9
A genomic approach to mutation analysis of holocarboxylase synthetase gene in three Chinese patients with late-onset holocarboxylase synthetase deficiency. 54 61
12633764 2003
10
Normalization of low biotinidase activity in a child with biotin deficiency after biotin supplementation. 54 61
14707523 2003
11
Holocarboxylase synthetase is an obligate participant in biotin-mediated regulation of its own expression and of biotin-dependent carboxylases mRNA levels in human cells. 61 54
11959985 2002
12
Structure of human holocarboxylase synthetase gene and mutation spectrum of holocarboxylase synthetase deficiency. 54 61
11735028 2001
13
Relationship between kinetic properties of mutant enzyme and biochemical and clinical responsiveness to biotin in holocarboxylase synthetase deficiency. 61 54
10590022 1999
14
Prenatal diagnosis of holocarboxylase synthetase deficiency by assay of the enzyme in chorionic villus material followed by prenatal treatment. 54 61
10437643 1999
15
Mechanism of biotin responsiveness in biotin-responsive multiple carboxylase deficiency. 54 61
10068510 1999
16
Detection of inborn errors of metabolism in Thai infants via gas chromatography and mass spectrometry. 54 61
11400759 1999
17
[Holocarboxylase synthetase deficiency (early-onset multiple carboxylase deficiency)]. 54 61
9645047 1998
18
Characterization of mutant holocarboxylase synthetase (HCS): a Km for biotin was not elevated in a patient with HCS deficiency. 54 61
9396568 1997
19
Multiple carboxylase deficiency: inherited and acquired disorders of biotin metabolism. 61 54
9350481 1997
20
Clustering of mutations in the biotin-binding region of holocarboxylase synthetase in biotin-responsive multiple carboxylase deficiency. 54 61
8817339 1996
21
Late-onset holocarboxylase synthetase deficiency. 54 61
8982946 1996
22
[Cloning of the holocarboxylase synthetase cDNA and identification of mutations prevalent in Japanese HCS-deficient patients]. 61 54
8587199 1996
23
Isolation and characterization of mutations in the human holocarboxylase synthetase cDNA. 61 54
7842009 1994
24
Holocarboxylase synthetase deficiency: early diagnosis and management of a new case. 61 54
8319716 1993
25
[Quantitative analysis of urinary organic acid]. 61 54
1507493 1992
26
Neonatal screening for biotinidase deficiency. 54 61
1503382 1992
27
Neonatal screening for biotinidase deficiency in east-Hungary. 61 54
1779652 1991
28
Fatty acid transport in multiple carboxylase deficiency fibroblasts. 61 54
2123277 1990
29
Partial Biotinidase Deficiency Revealed Imbalances in Acylcarnitines Profile at Tandem Mass Spectrometry Newborn Screening. 61
33572391 2021
30
Multiple Carboxylase Deficiency Organic Acidemia as a Cause of Infantile Seizures. 61
33546543 2021
31
Impaired glucose homeostasis and a novel HLCS pathogenic variant in holocarboxylase synthetase deficiency: a report of two cases and brief review. 61
32841162 2020
32
Clinical, biochemical, and genetic analysis of a Chinese Han pedigree with holocarboxylase synthetase deficiency: a case report. 61
32727382 2020
33
Spinal cord demyelination in children: A diagnostic challenge in neuropaediatrics for a good outcome. 61
32209270 2020
34
Case report of holocarboxylase synthetase deficiency (late-onset) in 2 Chinese patients. 61
32358368 2020
35
[Gene variant analysis of a patient with multiple carboxylase deficiency]. 61
32219826 2020
36
Biochemical signatures mimicking multiple carboxylase deficiency in children with mutations in MT-ATP6. 61
29307858 2019
37
Psoriasis-like Dermatitis in Adulthood: A Skin Manifestation of Holocarboxylase Synthetase Deficiency. 61
29701239 2018
38
Inborn errors of metabolism associated with hyperglycaemic ketoacidosis and diabetes mellitus: narrative review. 61
30166758 2018
39
Audit of Organic Acidurias from a Single Centre: Clinical and Metabolic Profile at Presentation with Long Term Outcome. 61
29207797 2017
40
[Screening for newborn organic aciduria in Zhejiang province:prevalence, outcome and follow-up]. 61
29039164 2017
41
Selective Screening for Organic Acidurias and Amino Acidopathies in Pakistani Children. 61
28492150 2017
42
Paracentric Inversion of Chromosome 21 Leading to Disruption of the HLCS Gene in a Family with Holocarboxylase Synthetase Deficiency. 61
27518780 2017
43
Leigh-Like Syndrome Due to Homoplasmic m.8993T>G Variant with Hypocitrullinemia and Unusual Biochemical Features Suggestive of Multiple Carboxylase Deficiency (MCD). 61
27450367 2017
44
Erratum: Leigh-Like Syndrome Due to Homoplasmic m.8993T>G Variant with Hypocitrullinemia and Unusual Biochemical Features Suggestive of Multiple Carboxylase Deficiency (MCD). 61
29076057 2017
45
Holocarboxylase synthetase deficiency pre and post newborn screening. 61
27114915 2016
46
Antenatal and postnatal radiologic diagnosis of holocarboxylase synthetase deficiency: a systematic review. 61
26754537 2016
47
Carbonic Anhydrase VA Deficiency 61
25834911 2015
48
Detection of inborn errors of metabolism using GC-MS: over 3 years of experience in southern China. 61
25781538 2015
49
An Economic Evaluation of Neonatal Screening for Inborn Errors of Metabolism Using Tandem Mass Spectrometry in Thailand. 61
26258410 2015
50
Severe neonatal holocarboxylase synthetase deficiency in west african siblings. 61
25690727 2015

Variations for Multiple Carboxylase Deficiency

Expression for Multiple Carboxylase Deficiency

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

Pathways for Multiple Carboxylase Deficiency

Pathways related to Multiple Carboxylase Deficiency according to GeneCards Suite gene sharing:

(show all 17)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.76 VNN2 SLC5A6 PNPO PCCB PCCA PC
2
Show member pathways
12.76 PCCB PCCA HADHA HADH ACADM ACACA
3
Show member pathways
12.3 HADHA HADH ACADM ACACA
4
Show member pathways
12.16 PCCB PCCA PC OTC
5
Show member pathways
12.01 VNN2 SLC5A6 PNPO PCCB PCCA PC
6
Show member pathways
11.87 PCCB PCCA MCCC2 MCCC1 HADHA HADH
7
Show member pathways
11.77 PCCB PCCA PC MCCC2 MCCC1 ACACA
8 11.76 PC OTC MCCC1 HADH ACADM
9
Show member pathways
11.59 PCCB PCCA HADHA HADH ACADM
10
Show member pathways
11.42 HADHA HADH ACADM
11 11.27 PCCB PCCA HADHA ACACA
12 11.04 PCCB PCCA
13 11 PC HADH ACACA
14 10.94 SLC5A6 BTD
15
Show member pathways
10.63 HADHA HADH ACADM
16
Show member pathways
10.51 PCCB PCCA PC MCCC2 MCCC1 ACACA
17 9.97 HLCS BTD

GO Terms for Multiple Carboxylase Deficiency

Cellular components related to Multiple Carboxylase Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 9.7 PCCB PCCA PC OTC MT-ATP6 MCCC2
2 mitochondrial matrix GO:0005759 9.28 PCCB PCCA PC OTC MCCC2 MCCC1
3 methylcrotonoyl-CoA carboxylase complex GO:1905202 9.26 MCCC2 MCCC1
4 3-methylcrotonyl-CoA carboxylase complex, mitochondrial GO:0002169 9.16 MCCC2 MCCC1

Biological processes related to Multiple Carboxylase Deficiency according to GeneCards Suite gene sharing:

(show all 11)
# Name GO ID Score Top Affiliating Genes
1 fatty acid metabolic process GO:0006631 9.73 HADHA HADH ACADM ACACA
2 metabolic process GO:0008152 9.71 PC HLCS HADHA ACACA
3 lipid metabolic process GO:0006629 9.63 PCCA PC HADHA HADH ACADM ACACA
4 fatty acid beta-oxidation GO:0006635 9.5 HADHA HADH ACADM
5 branched-chain amino acid catabolic process GO:0009083 9.49 MCCC2 MCCC1
6 nitrogen compound metabolic process GO:0006807 9.48 VNN2 BTD
7 pantothenate metabolic process GO:0015939 9.46 VNN2 SLC5A6
8 leucine catabolic process GO:0006552 9.37 MCCC2 MCCC1
9 short-chain fatty acid catabolic process GO:0019626 9.26 PCCB PCCA
10 biotin metabolic process GO:0006768 9.23 SLC5A6 PCCB PCCA PC MCCC2 MCCC1
11 response to biotin GO:0070781 8.96 OTC HLCS

Molecular functions related to Multiple Carboxylase Deficiency according to GeneCards Suite gene sharing:

(show all 12)
# Name GO ID Score Top Affiliating Genes
1 nucleotide binding GO:0000166 10.06 PCCB PCCA PC MOCS1 MCCC2 MCCC1
2 identical protein binding GO:0042802 10.05 PC OTC HLCS HADH ADSL ACADM
3 ATP binding GO:0005524 10.04 PCCB PCCA PC MCCC2 MCCC1 HLCS
4 catalytic activity GO:0003824 9.85 PC MOCS1 HLCS HADHA ADSL ACACA
5 ligase activity GO:0016874 9.5 PCCB PCCA PC MCCC2 MCCC1 HLCS
6 hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides GO:0016811 9.48 VNN2 BTD
7 3-hydroxyacyl-CoA dehydrogenase activity GO:0003857 9.43 HADHA HADH
8 acetyl-CoA carboxylase activity GO:0003989 9.4 PCCB ACACA
9 CoA carboxylase activity GO:0016421 9.32 PCCA MCCC1
10 propionyl-CoA carboxylase activity GO:0004658 9.26 PCCB PCCA
11 methylcrotonoyl-CoA carboxylase activity GO:0004485 9.16 MCCC2 MCCC1
12 biotin binding GO:0009374 8.92 PCCA PC MCCC1 HLCS

Sources for Multiple Carboxylase 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
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