MCD
MCID: MLT018
MIFTS: 41

Multiple Carboxylase Deficiency (MCD)

Categories: Metabolic diseases, Rare diseases

Aliases & Classifications for Multiple Carboxylase Deficiency

MalaCards integrated aliases for Multiple Carboxylase Deficiency:

Name: Multiple Carboxylase Deficiency 12 53 55 44 15 73
Holocarboxylase Synthetase Deficiency 73
Mcd 53

Classifications:



Summaries for Multiple Carboxylase Deficiency

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 148Disease definitionMultiple 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.EpidemiologyThe prevalence of MCD is unknown, but the condition is rare. There is no specific geographic or ethnic predominance.Clinical descriptionThere 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.EtiologyBiotinidase deficiency is caused by mutations in the BTD gene (3p25) and holocarboxylase synthetase deficiency by mutations in the HLCS gene (21q22.1).Genetic counselingBoth disorders are inherited as autosomal recessivetraits.Visit the Orphanet disease page for more resources.

MalaCards based summary : Multiple Carboxylase Deficiency, also known as holocarboxylase synthetase deficiency, is related to holocarboxylase synthetase deficiency and biotinidase deficiency, and has symptoms including seizures, vomiting and lethargy. An important gene associated with Multiple Carboxylase Deficiency is BTD (Biotinidase), and among its related pathways/superpathways are Metabolism and Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha). The drugs Biotin and Folic Acid have been mentioned in the context of this disorder. Affiliated tissues include skin, eye and liver, and related phenotypes are seizures and muscular hypotonia

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

Wikipedia : 76 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 all 48)
# Related Disease Score Top Affiliating Genes
1 holocarboxylase synthetase deficiency 33.6 BTD HLCS PC
2 biotinidase deficiency 33.3 BTD HLCS MCCC2 PCCB
3 biotin deficiency 31.6 ACACA BTD HLCS PC PCCB
4 multicentric castleman disease 12.1
5 malonyl-coa decarboxylase deficiency 12.0
6 macular dystrophy, corneal 11.9
7 metaphyseal chondrodysplasia, schmid type 11.8
8 kaposi sarcoma 11.8
9 focal segmental glomerulosclerosis 11.5
10 lipoid nephrosis 11.5
11 c1q nephropathy 11.1
12 corneal dystrophy, meesmann 11.0
13 metaphyseal dysplasia, spahr type 11.0
14 cortical malformations, occipital 11.0
15 microlissencephaly 11.0
16 castleman disease 10.3
17 sarcoma 10.2
18 focal segmental glomerulosclerosis 1 10.1
19 glomerulonephritis 10.1
20 liver disease 10.1
21 nonalcoholic fatty liver disease 10.1
22 nephrotic syndrome 10.1
23 fatty liver disease 10.1
24 kshv inflammatory cytokine syndrome 10.1
25 alopecia 10.1
26 lactic acidosis 10.1
27 acyl-coa dehydrogenase, medium-chain, deficiency of 10.0 ACADM BTD
28 monocarboxylate transporter 1 deficiency 10.0 HLCS PC
29 amino acid metabolic disorder 9.9 BTD PCCB
30 systemic lupus erythematosus 9.9
31 cortical dysplasia, complex, with other brain malformations 7 9.9
32 poems syndrome 9.9
33 epilepsy 9.9
34 lupus erythematosus 9.9
35 nonalcoholic steatohepatitis 9.9
36 diabetes mellitus, ketosis-prone 9.9
37 psoriasis 14, pustular 9.9
38 dermatitis 9.9
39 psoriasis 9.9
40 pustular psoriasis 9.9
41 hyperlysinemia, type i 9.8 OTC PC
42 3-hydroxyacyl-coa dehydrogenase deficiency 9.8 ACADM OTC
43 methylmalonic aciduria due to methylmalonyl-coa mutase deficiency 9.7 HLCS OTC PC
44 maple syrup urine disease 9.7 BTD OTC
45 phenylketonuria 9.7 ACADM BTD OTC
46 propionic acidemia 9.7 HLCS OTC PCCB
47 organic acidemia 9.7 ACADM BTD HLCS PCCB
48 reye syndrome 9.7 ACADM OTC PC

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:

32 (show all 14)
# Description HPO Frequency HPO Source Accession
1 seizures 32 hallmark (90%) HP:0001250
2 muscular hypotonia 32 hallmark (90%) HP:0001252
3 nausea and vomiting 32 hallmark (90%) HP:0002017
4 hearing impairment 32 hallmark (90%) HP:0000365
5 global developmental delay 32 hallmark (90%) HP:0001263
6 cognitive impairment 32 hallmark (90%) HP:0100543
7 abnormality of vision 32 frequent (33%) HP:0000504
8 abnormal blistering of the skin 32 hallmark (90%) HP:0008066
9 weight loss 32 frequent (33%) HP:0001824
10 alopecia 32 hallmark (90%) HP:0001596
11 skin rash 32 hallmark (90%) HP:0000988
12 lethargy 32 hallmark (90%) HP:0001254
13 inflammatory abnormality of the eye 32 hallmark (90%) HP:0100533
14 skin vesicle 32 hallmark (90%) HP:0200037

UMLS symptoms related to Multiple Carboxylase Deficiency:


seizures, vomiting, lethargy, exanthema

Drugs & Therapeutics for Multiple Carboxylase Deficiency

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

(show all 9)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Biotin Approved, Investigational, Nutraceutical Not Applicable 58-85-5 171548
2
Folic Acid Approved, Nutraceutical, Vet_approved Not Applicable 59-30-3 6037
3 Vitamin B9 Not Applicable
4 Vitamins Not Applicable
5 Micronutrients Not Applicable
6 Trace Elements Not Applicable
7 Folate Not Applicable
8 Vitamin B7 Not Applicable
9 Vitamin B Complex Not Applicable

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Study of ORL-1B in Patients With Biotinidase Deficiency Completed NCT03269045 Phase 1, Phase 2 ORL-1B
2 Biotin Status in Pregnancy Completed NCT00894920 Not Applicable
3 BIOtinidase Test In Optic-Neuropathy Completed NCT03268681
4 Biotin Deficiency and Restless Legs Syndrome Completed NCT02011191 Not Applicable

Search 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:

41
Skin, Eye, Liver, Brain

Publications for Multiple Carboxylase Deficiency

Articles related to Multiple Carboxylase Deficiency:

(show top 50) (show all 61)
# Title Authors Year
1
Biochemical signatures mimicking multiple carboxylase deficiency in children with mutations in MT-ATP6. ( 29307858 )
2018
2
Erratum: Leigh-Like Syndrome Due to Homoplasmic m.8993T>G Variant with Hypocitrullinemia and Unusual Biochemical Features Suggestive of Multiple Carboxylase Deficiency (MCD). ( 29076057 )
2017
3
Leigh-Like Syndrome Due to Homoplasmic m.8993T>G Variant with Hypocitrullinemia and Unusual Biochemical Features Suggestive of Multiple Carboxylase Deficiency (MCD). ( 27450367 )
2016
4
Holocarboxylase synthetase deficiency pre and post newborn screening. ( 27114915 )
2016
5
Multiple carboxylase deficiency (late onset) due to deficiency of biotinidase. ( 25284861 )
2014
6
[Gene mutation analyses in Chinese children with multiple carboxylase deficiency]. ( 19806568 )
2009
7
Determination of 3-hydroxyisovalerylcarnitine and other acylcarnitine levels using liquid chromatography-tandem mass spectrometry in serum and urine of a patient with multiple carboxylase deficiency. ( 18088573 )
2008
8
Reduced half-life of holocarboxylase synthetase from patients with severe multiple carboxylase deficiency. ( 18429047 )
2008
9
Impaired biotinidase activity disrupts holocarboxylase synthetase expression in late onset multiple carboxylase deficiency. ( 18845537 )
2008
10
[Gene mutation analysis in four Chinese patients with multiple carboxylase deficiency]. ( 17274881 )
2006
11
Biotin responsive multiple carboxylase deficiency presenting as diabetic ketoacidosis. ( 15095958 )
2004
12
Paradoxical regulation of biotin utilization in brain and liver and implications for inherited multiple carboxylase deficiency. ( 15456772 )
2004
13
Reduced histone biotinylation in multiple carboxylase deficiency patients: a nuclear role for holocarboxylase synthetase. ( 14613969 )
2004
14
Dermatologic signs of biotin deficiency leading to the diagnosis of multiple carboxylase deficiency. ( 15165201 )
2004
15
Mechanism of biotin responsiveness in biotin-responsive multiple carboxylase deficiency. ( 10068510 )
1999
16
[Holocarboxylase synthetase deficiency (early-onset multiple carboxylase deficiency)]. ( 9645047 )
1998
17
[Multiple carboxylase deficiency]. ( 9492625 )
1998
18
An unusual case of multiple carboxylase deficiency presenting as generalized pustular psoriasis in a Chinese boy. ( 9061576 )
1997
19
Multiple carboxylase deficiency: inherited and acquired disorders of biotin metabolism. ( 9350481 )
1997
20
Clustering of mutations in the biotin-binding region of holocarboxylase synthetase in biotin-responsive multiple carboxylase deficiency. ( 8817339 )
1996
21
Identification of 3-hydroxyisovalerylcarnitine in the urine of a patient with multiple carboxylase deficiency. ( 8517616 )
1993
22
Neonatal form of biotin-responsive multiple carboxylase deficiency. ( 1297821 )
1992
23
Fatty acid transport in multiple carboxylase deficiency fibroblasts. ( 2123277 )
1990
24
Biotin-responsive multiple carboxylase deficiency and immunodeficiency. ( 2663376 )
1989
25
Abnormal fatty acid composition of biotin-responsive multiple carboxylase deficiency fibroblasts. ( 2501583 )
1989
26
Biotin-responsive multiple carboxylase deficiency in an 8-year-old boy with normal serum biotinidase and fibroblast holocarboxylase-synthetase activities. ( 3148068 )
1988
27
Multiple carboxylase deficiency. ( 3284772 )
1988
28
Multiple carboxylase deficiency due to deficiency of biotinidase. ( 3783319 )
1986
29
Heterogeneity of holocarboxylase synthetase in patients with biotin-responsive multiple carboxylase deficiency. ( 3920902 )
1985
30
Organic aciduria in late-onset biotin-responsive multiple carboxylase deficiency. ( 3930851 )
1985
31
Lipid metabolism in biotin-responsive multiple carboxylase deficiency. ( 2878112 )
1985
32
Prenatal treatment of multiple carboxylase deficiency. ( 3925857 )
1985
33
Biotin-responsive multiple carboxylase deficiency (MCD): deficient biotinidase activity associated with renal loss of biotin. ( 6434862 )
1984
34
Acetyl CoA carboxylase in cultured fibroblasts: differential biotin dependence in the two types of biotin-responsive multiple carboxylase deficiency. ( 6141728 )
1984
35
Biotinidase deficiency in juvenile multiple carboxylase deficiency. ( 6135890 )
1983
36
Alopecia and periorificial dermatitis in biotin-responsive multiple carboxylase deficiency. ( 6886110 )
1983
37
Impaired intestinal absorption of biotin in juvenile multiple carboxylase deficiency. ( 6828095 )
1983
38
Deficient biotinidase activity in late-onset multiple carboxylase deficiency. ( 6848914 )
1983
39
Deficient liver biotinidase activity in multiple carboxylase deficiency. ( 6135889 )
1983
40
Biotinidase deficiency: the enzymatic defect in late-onset multiple carboxylase deficiency. ( 6883721 )
1983
41
Protein-bound biotin: a consideration in multiple carboxylase deficiency. ( 6119473 )
1982
42
Evidence for a defect of holocarboxylase synthetase activity in cultured lymphoblasts from a patient with biotin-responsive multiple carboxylase deficiency. ( 7102675 )
1982
43
Biochemical evidence for diverse etiologies in biotin-responsive multiple carboxylase deficiency. ( 6807281 )
1982
44
Biotin-responsive immunoregulatory dysfunction in multiple carboxylase deficiency. ( 6212592 )
1982
45
Prenatal administration of biotin in biotin responsive multiple carboxylase deficiency. ( 6799930 )
1982
46
Infantile multiple carboxylase deficiency: evidence for normal intestinal absorption but renal loss of biotin. ( 6819258 )
1982
47
Lactic acidosis in biotin-responsive multiple carboxylase deficiency caused by holocarboxylase synthetase deficiency of early and late onset. ( 6811711 )
1982
48
Prenatal treatment of biotin responsive multiple carboxylase deficiency. ( 6123722 )
1982
49
Organic aciduria in neonatal multiple carboxylase deficiency. ( 6820414 )
1982
50
Defective biotin absorption in multiple carboxylase deficiency. ( 6114319 )
1981

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 14)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.64 ACACA ACADM BTD HLCS MCCC2 OTC
2
Show member pathways
12.48 ACACA ACADM PCCB
3
Show member pathways
12.04 ACACA BTD HLCS MCCC2 PC PCCB
4
Show member pathways
11.95 ACADM OTC PC PCCB
5
Show member pathways
11.71 ACADM MCCC2 PCCB
6 11.57 ACADM OTC PC
7
Show member pathways
11.49 ACACA ACADM
8
Show member pathways
11.43 ACACA MCCC2 PC PCCB
9
Show member pathways
11.33 ACADM PCCB
10
Show member pathways
11.12 ACACA PC
11 10.94 ACACA ACADM PCCB
12 10.82 ACACA PC
13
Show member pathways
10 ACACA MCCC2 PC PCCB
14 9.85 BTD HLCS

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 9.43 ACADM HLCS MCCC2 OTC PC PCCB
2 mitochondrial matrix GO:0005759 9.1 ACADM BTD MCCC2 OTC PC PCCB

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

# Name GO ID Score Top Affiliating Genes
1 lipid metabolic process GO:0006629 9.5 ACACA ACADM PC
2 metabolic process GO:0008152 9.33 ACACA HLCS PC
3 fatty acid biosynthetic process GO:0006633 9.26 ACACA PCCB
4 biotin metabolic process GO:0006768 9.02 BTD HLCS MCCC2 PC PCCB
5 response to biotin GO:0070781 8.96 HLCS OTC

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

# Name GO ID Score Top Affiliating Genes
1 ATP binding GO:0005524 9.65 ACACA HLCS MCCC2 PC PCCB
2 catalytic activity GO:0003824 9.5 ACACA HLCS PC
3 biotin binding GO:0009374 9.16 HLCS PC
4 ligase activity GO:0016874 9.02 ACACA HLCS MCCC2 PC PCCB
5 acetyl-CoA carboxylase activity GO:0003989 8.96 ACACA PCCB

Sources for Multiple 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
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