MCID: MLT018
MIFTS: 45

Multiple Carboxylase Deficiency

Categories: Rare diseases, Metabolic diseases

Aliases & Classifications for Multiple Carboxylase Deficiency

MalaCards integrated aliases for Multiple Carboxylase Deficiency:

Name: Multiple Carboxylase Deficiency 12 49 51 41 14 69
Holocarboxylase Synthetase Deficiency 69
Mcd 49

Classifications:



Summaries for Multiple Carboxylase Deficiency

NIH Rare Diseases : 49 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. Last updated: 7/5/2011

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 hearing impairment, abnormality of vision and skin rash. An important gene associated with Multiple Carboxylase Deficiency is HLCS (Holocarboxylase Synthetase), and among its related pathways/superpathways are Metabolism and HIV Life Cycle. The drugs Biotin and Folic Acid have been mentioned in the context of this disorder. Affiliated tissues include skin, eye and testes.

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

Wikipedia : 72 Multiple carboxylase deficiency is a form of metabolic disorder involving failures of carboxylation... more...

Related Diseases for Multiple Carboxylase Deficiency

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:

31 (show all 14)
# Description HPO Frequency HPO Source Accession
1 hearing impairment 31 hallmark (90%) HP:0000365
2 abnormality of vision 31 frequent (33%) HP:0000504
3 skin rash 31 hallmark (90%) HP:0000988
4 seizures 31 hallmark (90%) HP:0001250
5 muscular hypotonia 31 hallmark (90%) HP:0001252
6 lethargy 31 hallmark (90%) HP:0001254
7 global developmental delay 31 hallmark (90%) HP:0001263
8 alopecia 31 hallmark (90%) HP:0001596
9 weight loss 31 frequent (33%) HP:0001824
10 nausea and vomiting 31 hallmark (90%) HP:0002017
11 abnormal blistering of the skin 31 hallmark (90%) HP:0008066
12 inflammatory abnormality of the eye 31 hallmark (90%) HP:0100533
13 cognitive impairment 31 hallmark (90%) HP:0100543
14 skin vesicle 31 hallmark (90%) HP:0200037

UMLS symptoms related to Multiple Carboxylase Deficiency:


vomiting, seizures, 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 58-85-5 171548
2
Folic Acid Approved, Nutraceutical, Vet_approved 59-30-3 6037
3 Micronutrients
4 Trace Elements
5 Vitamin B Complex
6 Vitamins
7 Folate Nutraceutical
8 Vitamin B7 Nutraceutical
9 Vitamin B9 Nutraceutical

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
3 Biotin Deficiency and Restless Legs Syndrome Completed NCT02011191
4 BIOtinidase Test In Optic-Neuropathy Recruiting NCT03268681

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:

38
Skin, Eye, Testes, Liver, Brain

Publications for Multiple Carboxylase Deficiency

Articles related to Multiple Carboxylase Deficiency:

(show top 50) (show all 58)
# 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
Multiple carboxylase deficiency (late onset) due to deficiency of biotinidase. ( 25284861 )
2014
5
[Gene mutation analyses in Chinese children with multiple carboxylase deficiency]. ( 19806568 )
2009
6
Impaired biotinidase activity disrupts holocarboxylase synthetase expression in late onset multiple carboxylase deficiency. ( 18845537 )
2008
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
[Gene mutation analysis in four Chinese patients with multiple carboxylase deficiency]. ( 17274881 )
2006
10
Dermatologic signs of biotin deficiency leading to the diagnosis of multiple carboxylase deficiency. ( 15165201 )
2004
11
Reduced histone biotinylation in multiple carboxylase deficiency patients: a nuclear role for holocarboxylase synthetase. ( 14613969 )
2004
12
Biotin responsive multiple carboxylase deficiency presenting as diabetic ketoacidosis. ( 15095958 )
2004
13
Paradoxical regulation of biotin utilization in brain and liver and implications for inherited multiple carboxylase deficiency. ( 15456772 )
2004
14
Mechanism of biotin responsiveness in biotin-responsive multiple carboxylase deficiency. ( 10068510 )
1999
15
[Multiple carboxylase deficiency]. ( 9492625 )
1998
16
[Holocarboxylase synthetase deficiency (early-onset multiple carboxylase deficiency)]. ( 9645047 )
1998
17
Multiple carboxylase deficiency: inherited and acquired disorders of biotin metabolism. ( 9350481 )
1997
18
An unusual case of multiple carboxylase deficiency presenting as generalized pustular psoriasis in a Chinese boy. ( 9061576 )
1997
19
Clustering of mutations in the biotin-binding region of holocarboxylase synthetase in biotin-responsive multiple carboxylase deficiency. ( 8817339 )
1996
20
Identification of 3-hydroxyisovalerylcarnitine in the urine of a patient with multiple carboxylase deficiency. ( 8517616 )
1993
21
Neonatal form of biotin-responsive multiple carboxylase deficiency. ( 1297821 )
1992
22
Fatty acid transport in multiple carboxylase deficiency fibroblasts. ( 2123277 )
1990
23
Abnormal fatty acid composition of biotin-responsive multiple carboxylase deficiency fibroblasts. ( 2501583 )
1989
24
Biotin-responsive multiple carboxylase deficiency and immunodeficiency. ( 2663376 )
1989
25
Multiple carboxylase deficiency. ( 3284772 )
1988
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 due to deficiency of biotinidase. ( 3783319 )
1986
28
Prenatal treatment of multiple carboxylase deficiency. ( 3925857 )
1985
29
Organic aciduria in late-onset biotin-responsive multiple carboxylase deficiency. ( 3930851 )
1985
30
Heterogeneity of holocarboxylase synthetase in patients with biotin-responsive multiple carboxylase deficiency. ( 3920902 )
1985
31
Lipid metabolism in biotin-responsive multiple carboxylase deficiency. ( 2878112 )
1985
32
Biotin-responsive multiple carboxylase deficiency (MCD): deficient biotinidase activity associated with renal loss of biotin. ( 6434862 )
1984
33
Acetyl CoA carboxylase in cultured fibroblasts: differential biotin dependence in the two types of biotin-responsive multiple carboxylase deficiency. ( 6141728 )
1984
34
Alopecia and periorificial dermatitis in biotin-responsive multiple carboxylase deficiency. ( 6886110 )
1983
35
Impaired intestinal absorption of biotin in juvenile multiple carboxylase deficiency. ( 6828095 )
1983
36
Biotinidase deficiency in juvenile multiple carboxylase deficiency. ( 6135890 )
1983
37
Deficient liver biotinidase activity in multiple carboxylase deficiency. ( 6135889 )
1983
38
Deficient biotinidase activity in late-onset multiple carboxylase deficiency. ( 6848914 )
1983
39
Biotinidase deficiency: the enzymatic defect in late-onset multiple carboxylase deficiency. ( 6883721 )
1983
40
Organic aciduria in neonatal multiple carboxylase deficiency. ( 6820414 )
1982
41
Prenatal treatment of biotin responsive multiple carboxylase deficiency. ( 6123722 )
1982
42
Biochemical evidence for diverse etiologies in biotin-responsive multiple carboxylase deficiency. ( 6807281 )
1982
43
Infantile multiple carboxylase deficiency: evidence for normal intestinal absorption but renal loss of biotin. ( 6819258 )
1982
44
Lactic acidosis in biotin-responsive multiple carboxylase deficiency caused by holocarboxylase synthetase deficiency of early and late onset. ( 6811711 )
1982
45
Biotin-responsive immunoregulatory dysfunction in multiple carboxylase deficiency. ( 6212592 )
1982
46
Evidence for a defect of holocarboxylase synthetase activity in cultured lymphoblasts from a patient with biotin-responsive multiple carboxylase deficiency. ( 7102675 )
1982
47
Protein-bound biotin: a consideration in multiple carboxylase deficiency. ( 6119473 )
1982
48
Prenatal administration of biotin in biotin responsive multiple carboxylase deficiency. ( 6799930 )
1982
49
Multiple carboxylase deficiency: clinical and biochemical improvement following neonatal biotin treatment. ( 6787561 )
1981
50
Biotin-responsive multiple carboxylase deficiency of infantile onset. ( 7264799 )
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 BTD HLCS MCCC2 OTC PC
2
Show member pathways
13.3 ACACA MCCC2 PC PCCA PCCB
3
Show member pathways
12.11 ACACA BTD HLCS MCCC2 PC PCCA
4
Show member pathways
11.94 OTC PC PCCA PCCB
5
Show member pathways
11.68 MCCC2 PCCA PCCB
6
Show member pathways
11.54 ACACA MCCC2 PC PCCA PCCB
7 11.48 OTC PC
8
Show member pathways
11.33 PCCA PCCB
9
Show member pathways
11.12 ACACA PC
10 10.94 ACACA PCCA PCCB
11 10.92 PCCA PCCB
12 10.8 ACACA PC
13
Show member pathways
10.1 ACACA MCCC2 PC PCCA 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 9.5 ACACA HLCS MCCC2 OTC PC PCCA
2 mitochondrial matrix GO:0005759 9.1 BTD MCCC2 OTC PC PCCA PCCB

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

# Name GO ID Score Top Affiliating Genes
1 metabolic process GO:0008152 9.5 ACACA HLCS PC
2 fatty acid biosynthetic process GO:0006633 9.26 ACACA PCCB
3 biotin metabolic process GO:0006768 9.17 ACACA BTD HLCS MCCC2 PC PCCA
4 short-chain fatty acid catabolic process GO:0019626 9.16 PCCA 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 9.85 ACACA HLCS MCCC2 PC PCCA PCCB
2 catalytic activity GO:0003824 9.71 ACACA HLCS PC PCCA
3 biotin carboxylase activity GO:0004075 9.33 ACACA PC PCCA
4 acetyl-CoA carboxylase activity GO:0003989 9.32 ACACA PCCB
5 propionyl-CoA carboxylase activity GO:0004658 9.26 PCCA PCCB
6 biotin binding GO:0009374 9.13 HLCS PC PCCA
7 ligase activity GO:0016874 9.1 ACACA HLCS MCCC2 PC PCCA PCCB

Sources for Multiple 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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