MCID: HLC001
MIFTS: 59

Holocarboxylase Synthetase Deficiency malady

Skin diseases, Metabolic diseases, Ear diseases categories

Summaries for Holocarboxylase Synthetase Deficiency

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8Disease Ontology, 21Genetics Home Reference, 63Wikipedia, 46OMIM, 32MalaCards
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Genetics Home Reference:21 Holocarboxylase synthetase deficiency is an inherited disorder in which the body is unable to use the vitamin biotin effectively. This disorder is classified as a multiple carboxylase deficiency, a group of disorders characterized by impaired activity of certain enzymes that depend on biotin.

MalaCards: Holocarboxylase Synthetase Deficiency, also known as holocarboxylase synthetase, is related to biotinidase deficiency and multiple carboxylase deficiency, and has symptoms including thrombocytopenia/thrombopenia, obnubilation/coma/lethargia/desorientation and ataxia/incoordination/trouble of the equilibrium. An important gene associated with Holocarboxylase Synthetase Deficiency is HLCS (holocarboxylase synthetase (biotin-(proprionyl-CoA-carboxylase (ATP-hydrolysing)) ligase)), and among its related pathways are Biotin metabolism and Metabolism. The compounds multivitamin and valproic acid have been mentioned in the context of this disorder. Affiliated tissues include skin and lung.

Disease Ontology:8 A multiple carboxylase deficiency that involves a deficiency in holocarboxylase synthetase.

Wikipedia:63 Holocarboxylase synthetase deficiency is an inherited metabolic disorder in which the body is unable to... more...

Description from OMIM:46 253270

Aliases & Classifications for Holocarboxylase Synthetase Deficiency

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8Disease Ontology, 9diseasecard, 42NIH Rare Diseases, 21Genetics Home Reference, 46OMIM, 10DISEASES, 44Novoseek, 48Orphanet, 60UMLS, 20GeneTests, 22GTR, 56SNOMED-CT, 34MeSH, 57SNOMED-CT via Orphanet, 26ICD10 via Orphanet
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Classifications:

Malacards categories (disease lists): (See all malacards categories)
Global: Metabolic diseases
Anatomical: Skin diseases, Ear diseases


Characteristics (Orphanet epidemiological data):

48
holocarboxylase synthetase deficiency:
Inheritance: Autosomal recessive; Age of onset: Neonatal/infancy; Age of death: Any age


Aliases & Descriptions:

holocarboxylase synthetase deficiency 8 9 42 21 46 10 44 48 60
holocarboxylase synthetase 9 20 22
early-onset biotin-responsive multiple carboxylase deficiency 21
multiple carboxylase deficiency - neonatal onset 8
multiple carboxylase deficiency, neonatal form 21
early-onset combined carboxylase deficiency 21
early-onset multiple carboxylase deficiency 48
infantile multiple carboxylase deficiency 21
neonatal multiple carboxylase deficiency 48
biotin- ligase deficiency 8
hlcs deficiency 21


External Ids:

Disease Ontology8 DOID:859
MeSH34 D028922
OMIM46 253270
SNOMED-CT via Orphanet57 360369003
ICD10 via Orphanet26 E53.8

Related Diseases for Holocarboxylase Synthetase Deficiency

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Sources:
17GeneCards, 18GeneDecks
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Diseases related to Holocarboxylase Synthetase Deficiency via text searches within MalaCards or GeneCards/GeneDecks gene sharing:

(show all 18)
idRelated DiseaseScoreTop Affiliating Genes
1biotinidase deficiency30.6BTD, HLCS
2multiple carboxylase deficiency30.6PC, BTD, HLCS
3glycogen storage disease30.3BTD
4organic acidemia30.3BTD, HLCS
5lactic acidosis30.3PC, BTD
6biotin deficiency10.8
7cerebritis10.3
8cerebral palsy10.3
9down syndrome10.2
10propionic acidemia10.0HLCS
11alopecia10.0BTD
12reye syndrome10.0PC
13candidiasis10.0BTD
14methylmalonic acidemia10.0PC, HLCS
15brain disease10.0BTD, PC
16hypoglycemia10.0PC, BTD, HLCS
17metabolic acidosis10.0HLCS, BTD, PC
18metabolic syndrome x10.0PC, BTD, HLCS

Graphical network of diseases related to Holocarboxylase Synthetase Deficiency:



Diseases related to holocarboxylase synthetase deficiency

Clinical Features for Holocarboxylase Synthetase Deficiency

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Sources:
46OMIM, 48Orphanet
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Clinical features from OMIM:

253270

Clinical synopsis from OMIM:

253270

Symptoms:

48 (show all 17)
  • thrombocytopenia/thrombopenia
  • obnubilation/coma/lethargia/desorientation
  • ataxia/incoordination/trouble of the equilibrium
  • alopecia
  • dry/squaly skin/exfoliation
  • hyperammonemia
  • respiratory rhythm disorder
  • respiratory distress/dyspnea/respiratory failure/lung volume reduction
  • weight loss/loss of appetite/break in weight curve/general health alteration
  • failure to thrive/difficulties for feeding in infancy/growth delay
  • autosomal recessive inheritance
  • humour troubles/anxiety/depression/apathy/euphoria/irritability
  • seizures/epilepsy/absences/spasms/status epilepticus
  • hypotonia
  • nausea/vomiting/regurgitation/merycism/hyperemesis
  • oral mucosa disease/cheilitis
  • chronic uveitis/blepharitis/episcleritis/scleritis/conjonctivitis/keratitis

Drugs & Therapeutics for Holocarboxylase Synthetase Deficiency

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Sources:
5CenterWatch, 41NIH Clinical Center, 6ClinicalTrials, 60UMLS, 40NDF-RT
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Approved drugs:

Search CenterWatch for Holocarboxylase Synthetase Deficiency

Drug clinical trials:

Search ClinicalTrials for Holocarboxylase Synthetase Deficiency

Search NIH Clinical Center for Holocarboxylase Synthetase Deficiency

Search CenterWatch for Holocarboxylase Synthetase Deficiency

Genetic Tests for Holocarboxylase Synthetase Deficiency

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20GeneTests, 22GTR
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Genetic tests related to Holocarboxylase Synthetase Deficiency:

id Genetic test Affiliating Genes
1 Holocarboxylase Synthetase Deficiency20 22 HLCS

Anatomical Context for Holocarboxylase Synthetase Deficiency

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32MalaCards
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MalaCards organs/tissues related to Holocarboxylase Synthetase Deficiency:

32
Skin, Lung

Animal Models for Holocarboxylase Synthetase Deficiency or affiliated genes

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Publications for Holocarboxylase Synthetase Deficiency

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Sources:
50PubMed
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Articles related to Holocarboxylase Synthetase Deficiency:

(show top 50)    (show all 55)
idTitleAuthorsYear
1
Clinical Presentation and Positive Outcome of Two Siblings with Holocarboxylase Synthetase Deficiency Caused by a Homozygous L216R Mutation. (24085707)
2013
2
Holocarboxylase synthetase deficiency: novel clinical and molecular findings. (20095979)
2010
3
A case of holocarboxylase synthetase deficiency with insufficient response to prenatal biotin therapy. (19201116)
2009
4
Positive newborn screen in the biochemically normal infant of a mother with treated holocarboxylase synthetase deficiency. (19357990)
2009
5
Management of a patient with holocarboxylase synthetase deficiency. (18974016)
2008
6
Impaired biotinidase activity disrupts holocarboxylase synthetase expression in late onset multiple carboxylase deficiency. (18845537)
2008
7
Reduced half-life of holocarboxylase synthetase from patients with severe multiple carboxylase deficiency. (18429047)
2008
8
Microbial biotin protein ligases aid in understanding holocarboxylase synthetase deficiency. (18442489)
2008
9
Susceptibility to heat stress and aberrant gene expression patterns in holocarboxylase synthetase-deficient Drosophila melanogaster are caused by decreased biotinylation of histones, not of carboxylases. (17374649)
2007
10
Carnitine transporter and holocarboxylase synthetase deficiencies in The Faroe Islands. (17417720)
2007
11
Three congenital metabolic diseases in the Faeroe Islands. Incidence, clinical and molecular genetic characteristics of Faeroese children with glycogen storage disease type IIIA, carnitine transporter deficiency and holocarboxylase synthetase deficiency]. (16494802)
2006
12
Holocarboxylase synthetase deficiency presenting as ichthyosis. (16650223)
2006
13
First prenatal molecular diagnosis in a family with holocarboxylase synthetase deficiency. (16231399)
2005
14
Severe holocarboxylase synthetase deficiency with incomplete biotin responsiveness resulting in antenatal insult in samoan neonates. (16027709)
2005
15
Reduced histone biotinylation in multiple carboxylase deficiency patients: a nuclear role for holocarboxylase synthetase. (14613969)
2004
16
A genomic approach to mutation analysis of holocarboxylase synthetase gene in three Chinese patients with late-onset holocarboxylase synthetase deficiency. (12633764)
2003
17
Partial response to biotin therapy in a patient with holocarboxylase synthetase deficiency: clinical, biochemical, and molecular genetic aspects. (12855220)
2003
18
Clinical findings and biochemical and molecular analysis of four patients with holocarboxylase synthetase deficiency. (12124727)
2002
19
Structure of human holocarboxylase synthetase gene and mutation spectrum of holocarboxylase synthetase deficiency. (11735028)
2001
20
Holocarboxylase synthetase deficiency]. (11462701)
2001
21
Haplotype analysis suggests that the two predominant mutations in Japanese patients with holocarboxylase synthetase deficiency are founder mutations. (11185745)
2000
22
Diagnosis and molecular analysis of an atypical case of holocarboxylase synthetase deficiency. (10653324)
2000
23
Late-onset holocarboxylase synthetase deficiency with homologous R508W mutation. (10770035)
2000
24
Holocarboxylase synthetase deficiency: urinary metabolites masked by gross ketosis. (11196112)
2000
25
Identification and characterization of mutations in patients with holocarboxylase synthetase deficiency. (10190325)
1999
26
Prenatal diagnosis of holocarboxylase synthetase deficiency by assay of the enzyme in chorionic villus material followed by prenatal treatment. (10437643)
1999
27
Prenatal diagnosis and treatment of holocarboxylase synthetase deficiency. (10215065)
1999
28
Deficiency of biotinyl-AMP synthetase activity in fibroblasts of patients with holocarboxylase synthetase deficiency. (9758715)
1998
29
Holocarboxylase synthetase deficiency (early-onset multiple carboxylase deficiency)]. (9645047)
1998
30
Late-onset holocarboxylase synthetase-deficiency: pre- and post-natal diagnosis and evaluation of effectiveness of antenatal biotin therapy. (9686819)
1998
31
Molecular analysis of new Japanese patients with holocarboxylase synthetase deficiency. (9870216)
1998
32
Characterization of mutant holocarboxylase synthetase (HCS): a Km for biotin was not elevated in a patient with HCS deficiency. (9396568)
1997
33
Resolution of subependymal cysts in neonatal holocarboxylase synthetase deficiency. (9183268)
1997
34
Enzymatic diagnosis of holocarboxylase synthetase deficiency using apo-carboxyl carrier protein as a substrate. (8814349)
1996
35
Cloning of the holocarboxylase synthetase cDNA and identification of mutations prevalent in Japanese HCS-deficient patients]. (8587199)
1996
36
Late-onset holocarboxylase synthetase deficiency. (8982946)
1996
37
Clustering of mutations in the biotin-binding region of holocarboxylase synthetase in biotin-responsive multiple carboxylase deficiency. (8817339)
1996
38
Molecular analysis of holocarboxylase synthetase deficiency: a missense mutation and a single base deletion are predominant in Japanese patients. (8541348)
1995
39
Holocarboxylase synthetase deficiency: a treatable metabolic disorder masquerading as cerebral palsy. (8006369)
1994
40
Holocarboxylase synthetase deficiency: early diagnosis and management of a new case. (8319716)
1993
41
A new case of holocarboxylase synthetase deficiency. (2515377)
1989
42
Holocarboxylase synthetase deficiency: 9-year follow-up of a patient on chronic biotin therapy and a review of the literature. (2515372)
1989
43
Biotin-responsive multiple carboxylase deficiency in an 8-year-old boy with normal serum biotinidase and fibroblast holocarboxylase-synthetase activities. (3148068)
1988
44
Heterogeneity of holocarboxylase synthetase in patients with biotin-responsive multiple carboxylase deficiency. (3920902)
1985
45
Biotin holocarboxylase synthetase deficiency. (3860175)
1985
46
Lactic acidosis in biotin-responsive multiple carboxylase deficiency caused by holocarboxylase synthetase deficiency of early and late onset. (6811711)
1982
47
Evidence for a defect of holocarboxylase synthetase activity in cultured lymphoblasts from a patient with biotin-responsive multiple carboxylase deficiency. (7102675)
1982
48
Mutant holocarboxylase synthetase: evidence for the enzyme defect in early infantile biotin-responsive multiple carboxylase deficiency. (6798072)
1981
49
Serum and urinary biotin levels during treatment of holocarboxylase synthetase deficiency. (7226522)
1981
50
Holocarboxylase synthetase deficiency: a biotin-responsive organic acidemia. (7365583)
1980

Genetic Variations for Holocarboxylase Synthetase Deficiency

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62UniProtKB/Swiss-Prot
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Genetic disease variations for Holocarboxylase Synthetase Deficiency:

62 (show all 21)
id Symbol AA change Variation ID SNP ID
1HLCSp.Leu237ProVAR_005084
2HLCSp.Val333GluVAR_009196
3HLCSp.Thr462IleVAR_009197
4HLCSp.Val550MetVAR_009198
5HLCSp.Asp571AsnVAR_009199
6HLCSp.Gly581SerVAR_009200
7HLCSp.Arg508TrpVAR_013009
8HLCSp.Leu216ArgVAR_021218rs28934602
9HLCSp.Asn511LysVAR_021219
10HLCSp.Gly582ArgVAR_021220
11HLCSp.Arg183ProVAR_046507
12HLCSp.Arg360SerVAR_046508
13HLCSp.Val363AspVAR_046509
14HLCSp.Tyr456CysVAR_046510
15HLCSp.Leu470SerVAR_046511
16HLCSp.Gly518GluVAR_046512
17HLCSp.Val547GlyVAR_046513
18HLCSp.Asp615TyrVAR_046514
19HLCSp.Asp634AsnVAR_046515
20HLCSp.Asp634TyrVAR_046516
21HLCSp.Asp715GlyVAR_046517

Expression for genes affiliated with Holocarboxylase Synthetase Deficiency

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1BioGPS, 15Gene Expression Omnibus DataSets
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Expression patterns in normal tissues for genes affiliated with Holocarboxylase Synthetase Deficiency

Search GEO for disease gene expression data for Holocarboxylase Synthetase Deficiency.

Pathways for genes affiliated with Holocarboxylase Synthetase Deficiency

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29KEGG, 53Reactome, 37NCBI BioSystems Database
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Pathways related to Holocarboxylase Synthetase Deficiency according to GeneCards/GeneDecks:

idSuper pathways (with members indented)ScoreTop Affiliating Genes
19.3BTD, HLCS
2
Hide members
8.5PC, BTD, HLCS
3
Hide members
8.5HLCS, BTD, PC
4
Saturated fatty acid biosynthesis
Hide members
8.5PC, BTD, HLCS

Compounds for genes affiliated with Holocarboxylase Synthetase Deficiency

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44Novoseek, 49PharmGKB, 11DrugBank, 24HMDB
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Compounds related to Holocarboxylase Synthetase Deficiency according to GeneCards/GeneDecks:

(show all 13)
idCompoundScoreTop Affiliating Genes
1multivitamin449.5BTD, HLCS
2valproic acid44 49 11 2412.3SLC22A5, BTD
3pyruvate449.1PC, HLCS
4alpha lipoic acid449.1BTD, PC
5s-adenosylmethionine44 11 2411.0PC, HLCS
6carnitine448.9SLC22A5, PC, HLCS
7acetyl-coa44 249.8PC, HLCS
83-methylcrotonyl-coa44 249.8PC, BTD, HLCS
9acyl-coa448.8HLCS, BTD, PC
10biotin44 11 2410.7PC, BTD, HLCS
11fatty acid448.7HLCS, BTD, PC
12lysine448.7PC, BTD, HLCS
13lactate448.6PC, BTD, HLCS

GO Terms for genes affiliated with Holocarboxylase Synthetase Deficiency

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16Gene Ontology
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Biological processes related to Holocarboxylase Synthetase Deficiency according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1biotin metabolic processGO:0067688.5PC, BTD, HLCS
2small molecule metabolic processGO:0442818.5PC, BTD, HLCS
3water-soluble vitamin metabolic processGO:0067678.4PC, BTD, HLCS
4vitamin metabolic processGO:0067668.2HLCS, BTD, PC

Molecular functions related to Holocarboxylase Synthetase Deficiency according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1biotin bindingGO:0093749.0PC, HLCS
2biotin carboxylase activityGO:0040758.7PC, BTD
3ATP bindingGO:0055248.6SLC22A5, PC, HLCS

Products for genes affiliated with Holocarboxylase Synthetase Deficiency

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  • Antibodies
  • Proteins
  • Lysates
  • Antibodies

Sources for Holocarboxylase Synthetase Deficiency

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3CDC
13ExPASy
14FMA
22GTR
23HGMD
24HMDB
25ICD10
26ICD10 via Orphanet
27ICD9CM
28IUPHAR
29KEGG
34MeSH
35MESH via Orphanet
36MGI
39NCIt
40NDF-RT
43NINDS
44Novoseek
46OMIM
47OMIM via Orphanet
50PubMed
51QIAGEN
57SNOMED-CT via Orphanet
60UMLS
61UMLS via Orphanet