MCID: HLC001
MIFTS: 56

Holocarboxylase Synthetase Deficiency malady

Genetic diseases, Rare diseases, Skin diseases categories

Summaries for Holocarboxylase Synthetase Deficiency

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9Disease Ontology, 22Genetics Home Reference, 66Wikipedia, 48OMIM, 34MalaCards
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Genetics Home Reference:22 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 multiple carboxylase deficiency and organic acidemia, and has symptoms including hyperammonemia, alopecia and chronic uveitis/blepharitis/episcleritis/scleritis/conjonctivitis/keratitis. 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 Defective BTD causes biotidinase deficiency. The compounds carnitine and s-adenosylmethionine have been mentioned in the context of this disorder. Affiliated tissues include skin and lung.

Disease Ontology:9 A multiple carboxylase deficiency that involves a deficiency in holocarboxylase synthetase.

Wikipedia:66 Holocarboxylase synthetase deficiency is an inherited metabolic disorder in which the body is unable to... more...

Description from OMIM:48 253270

Aliases & Classifications for Holocarboxylase Synthetase Deficiency

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9Disease Ontology, 10diseasecard, 44NIH Rare Diseases, 22Genetics Home Reference, 48OMIM, 11DISEASES, 46Novoseek, 50Orphanet, 63UMLS, 21GeneTests, 23GTR, 59SNOMED-CT, 36MeSH, 60SNOMED-CT via Orphanet, 64UMLS via Orphanet, 37MESH via Orphanet, 27ICD10 via Orphanet
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Classifications:

Malacards categories (disease lists): (See all malacards categories)
Global: Genetic diseases, Rare diseases
Anatomical: Skin diseases


Characteristics (Orphanet epidemiological data):

50
holocarboxylase synthetase deficiency:
Inheritance: Autosomal recessive; Age of onset: Neonatal/infancy; Age of death: Any age


Aliases & Descriptions:

holocarboxylase synthetase deficiency 9 10 44 22 48 11 46 50 63
holocarboxylase synthetase 10 21 23
early-onset biotin-responsive multiple carboxylase deficiency 22
multiple carboxylase deficiency - neonatal onset 9
multiple carboxylase deficiency, neonatal form 22
early-onset combined carboxylase deficiency 22
early-onset multiple carboxylase deficiency 50
infantile multiple carboxylase deficiency 22
neonatal multiple carboxylase deficiency 50
biotin- ligase deficiency 9
hlcs deficiency 22


External Ids:

Disease Ontology9 DOID:859
MeSH36 D028922
OMIM48 253270
SNOMED-CT via Orphanet60 360369003
UMLS via Orphanet64 C0268581
MESH via Orphanet37 D028922
ICD10 via Orphanet27 E53.8

Related Diseases for Holocarboxylase Synthetase Deficiency

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18GeneCards, 19GeneDecks
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Diseases related to Holocarboxylase Synthetase Deficiency via text searches within MalaCards or GeneCards/GeneDecks gene sharing:

(show all 15)
idRelated DiseaseScoreTop Affiliating Genes
1multiple carboxylase deficiency30.6PC, HLCS, BTD
2organic acidemia30.4BTD, HLCS
3lactic acidosis30.4PC, BTD
4biotinidase deficiency30.3HLCS, BTD
5biotin deficiency10.3
6cerebritis10.3
7cerebral palsy10.3
8glycogen storage disease10.3
9down syndrome10.2
10methylmalonic acidemia10.0HLCS, PC
11dermatitis10.0BTD, HLCS
12brain disease9.9PC, BTD
13metabolic acidosis9.9HLCS, BTD, PC
14hypoglycemia9.9BTD, PC, HLCS
15metabolic syndrome x9.9BTD, PC, HLCS

Graphical network of diseases related to Holocarboxylase Synthetase Deficiency:



Diseases related to holocarboxylase synthetase deficiency

Symptoms for Holocarboxylase Synthetase Deficiency

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48OMIM, 50Orphanet
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Symptoms by clinical synopsis from OMIM:

253270

Clinical features from OMIM:

253270

Symptoms:

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

Drugs & Therapeutics for Holocarboxylase Synthetase Deficiency

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Sources:
6CenterWatch, 43NIH Clinical Center, 7ClinicalTrials, 63UMLS, 42NDF-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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21GeneTests, 23GTR
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Genetic tests related to Holocarboxylase Synthetase Deficiency:

id Genetic test Affiliating Genes
1 Holocarboxylase Synthetase Deficiency21 23 HLCS

Anatomical Context for Holocarboxylase Synthetase Deficiency

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34MalaCards
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MalaCards organs/tissues related to Holocarboxylase Synthetase Deficiency:

34
Skin, Lung

Animal Models for Holocarboxylase Synthetase Deficiency or affiliated genes

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Publications for Holocarboxylase Synthetase Deficiency

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53PubMed
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Articles related to Holocarboxylase Synthetase Deficiency:

(show all 45)
idTitleAuthorsYear
1
Clinical Presentation and Positive Outcome of Two Siblings with Holocarboxylase Synthetase Deficiency Caused by a Homozygous L216R Mutation. (24085707)
2013
2
A novel molecular mechanism to explain biotin-unresponsive holocarboxylase synthetase deficiency. (21894551)
2012
3
The first reported HLCS gene mutation causing holocarboxylase synthetase deficiency in a Vietnamese patient. (21874615)
2012
4
Holocarboxylase synthetase deficiency: novel clinical and molecular findings. (20095979)
2010
5
A case of holocarboxylase synthetase deficiency with insufficient response to prenatal biotin therapy. (19201116)
2009
6
Positive newborn screen in the biochemically normal infant of a mother with treated holocarboxylase synthetase deficiency. (19357990)
2009
7
Management of a patient with holocarboxylase synthetase deficiency. (18974016)
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
Holocarboxylase synthetase deficiency: report of one case. (17407983)
2006
14
First prenatal molecular diagnosis in a family with holocarboxylase synthetase deficiency. (16231399)
2005
15
Severe holocarboxylase synthetase deficiency with incomplete biotin responsiveness resulting in antenatal insult in samoan neonates. (16027709)
2005
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
Holocarboxylase synthetase deficiency: report of a case with onset in late infancy. (10234606)
1999
26
Relationship between kinetic properties of mutant enzyme and biochemical and clinical responsiveness to biotin in holocarboxylase synthetase deficiency. (10590022)
1999
27
Identification and characterization of mutations in patients with holocarboxylase synthetase deficiency. (10190325)
1999
28
Prenatal diagnosis of holocarboxylase synthetase deficiency by assay of the enzyme in chorionic villus material followed by prenatal treatment. (10437643)
1999
29
Prenatal diagnosis and treatment of holocarboxylase synthetase deficiency. (10215065)
1999
30
Deficiency of biotinyl-AMP synthetase activity in fibroblasts of patients with holocarboxylase synthetase deficiency. (9758715)
1998
31
Holocarboxylase synthetase deficiency (early-onset multiple carboxylase deficiency)]. (9645047)
1998
32
Late-onset holocarboxylase synthetase-deficiency: pre- and post-natal diagnosis and evaluation of effectiveness of antenatal biotin therapy. (9686819)
1998
33
Molecular analysis of new Japanese patients with holocarboxylase synthetase deficiency. (9870216)
1998
34
Resolution of subependymal cysts in neonatal holocarboxylase synthetase deficiency. (9183268)
1997
35
Enzymatic diagnosis of holocarboxylase synthetase deficiency using apo-carboxyl carrier protein as a substrate. (8814349)
1996
36
Late-onset holocarboxylase synthetase deficiency. (8982946)
1996
37
Molecular analysis of holocarboxylase synthetase deficiency: a missense mutation and a single base deletion are predominant in Japanese patients. (8541348)
1995
38
Holocarboxylase synthetase deficiency: a treatable metabolic disorder masquerading as cerebral palsy. (8006369)
1994
39
Holocarboxylase synthetase deficiency: early diagnosis and management of a new case. (8319716)
1993
40
A new case of holocarboxylase synthetase deficiency. (2515377)
1989
41
Holocarboxylase synthetase deficiency: 9-year follow-up of a patient on chronic biotin therapy and a review of the literature. (2515372)
1989
42
Biotin holocarboxylase synthetase deficiency. (3860175)
1985
43
Lactic acidosis in biotin-responsive multiple carboxylase deficiency caused by holocarboxylase synthetase deficiency of early and late onset. (6811711)
1982
44
Serum and urinary biotin levels during treatment of holocarboxylase synthetase deficiency. (7226522)
1981
45
Holocarboxylase synthetase deficiency: a biotin-responsive organic acidemia. (7365583)
1980

Variations for Holocarboxylase Synthetase Deficiency

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Sources:
65UniProtKB/Swiss-Prot, 1 National Center for Biotechnology Information (Clinvar), 8dbSNP
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UniProtKB/Swiss-Prot genetic disease variations for Holocarboxylase Synthetase Deficiency:

65 (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_021220rs376899782
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_046515rs149399432
20HLCSp.Asp634TyrVAR_046516
21HLCSp.Asp715GlyVAR_046517

Clinvar genetic disease variations for Holocarboxylase Synthetase Deficiency:

1
id Gene Name Type Significance SNP ID Assembly Location
1HLCSHLCS, 1-BP DEL, 780GdeletionPathogenic
2HLCSNM_000411.6(HLCS): c.710T> C (p.Leu237Pro)single nucleotide variantPathogenicrs119103227GRCh37Chr 21, 38309035: 38309035
3HLCSNM_000411.6(HLCS): c.1711G> A (p.Asp571Asn)single nucleotide variantPathogenicrs119103228GRCh37Chr 21, 38132112: 38132112
4HLCSNM_000411.6(HLCS): c.1522C> T (p.Arg508Trp)single nucleotide variantPathogenicrs119103229GRCh37Chr 21, 38137471: 38137471
5HLCSNM_000411.6(HLCS): c.1741G> A (p.Gly581Ser)single nucleotide variantPathogenicrs119103230GRCh37Chr 21, 38132082: 38132082
6HLCSNM_000411.6(HLCS): c.1648G> A (p.Val550Met)single nucleotide variantPathogenicrs119103231GRCh37Chr 21, 38137345: 38137345
7HLCSHLCS, IVS10, G-A, +5single nucleotide variantPathogenic
8HLCSHLCS, 1-BP INS, 655AinsertionPathogenic
9HLCSNM_000411.6(HLCS): c.647T> G (p.Leu216Arg)single nucleotide variantPathogenicrs28934602GRCh37Chr 21, 38309098: 38309098

Expression for genes affiliated with Holocarboxylase Synthetase Deficiency

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2BioGPS, 16Gene 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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51PathCards, 31KEGG, 56Reactome, 39NCBI BioSystems Database
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Pathways related to Holocarboxylase Synthetase Deficiency according to GeneCards/GeneDecks:

idSuper pathways (with members indented)ScoreTop Affiliating Genes
19.0BTD, HLCS
2
Show member pathways
flavin biosynthesis IV (mammalian)39
molybdenum cofactor biosynthesis39
coenzyme A biosynthesis39
thiamin salvage III39
alanine biosynthesis III39
thio-molybdenum cofactor biosynthesis39
biotin-carboxyl carrier protein assembly39
8.5BTD, PC, HLCS
3
Show member pathways
8.5BTD, PC, HLCS
48.5HLCS, PC, BTD

Compounds for genes affiliated with Holocarboxylase Synthetase Deficiency

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46Novoseek, 25HMDB, 12DrugBank
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Compounds related to Holocarboxylase Synthetase Deficiency according to GeneCards/GeneDecks:

(show all 14)
idCompoundScoreTop Affiliating Genes
1carnitine469.4PC, HLCS
2s-adenosylmethionine46 25 1211.4PC, HLCS
3acetyl-coa46 2510.3HLCS, PC
4alpha lipoic acid469.3BTD, PC
5multivitamin469.3HLCS, BTD
6pyruvate469.2PC, HLCS
7zinc46 2510.1BTD, PC
8glycogen46 259.8BTD, PC
93-methylcrotonyl-coa46 259.8BTD, PC, HLCS
10acyl-coa468.8HLCS, PC, BTD
11biotin46 25 1210.8BTD, PC, HLCS
12fatty acid468.7BTD, PC, HLCS
13lysine468.7BTD, PC, HLCS
14lactate468.7HLCS, PC, BTD

GO Terms for genes affiliated with Holocarboxylase Synthetase Deficiency

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17Gene Ontology
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Cellular components related to Holocarboxylase Synthetase Deficiency according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1mitochondrial matrixGO:0057599.1BTD, PC

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

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

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

idNameGO IDScoreTop Affiliating Genes
1biotin carboxylase activityGO:0040759.1BTD, PC
2biotin bindingGO:0093749.0PC, 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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4CDC
14ExPASy
15FMA
23GTR
24HGMD
25HMDB
26ICD10
27ICD10 via Orphanet
28ICD9CM
30IUPHAR
31KEGG
36MeSH
37MESH via Orphanet
38MGI
41NCIt
42NDF-RT
45NINDS
46Novoseek
48OMIM
49OMIM via Orphanet
53PubMed
54QIAGEN
60SNOMED-CT via Orphanet
63UMLS
64UMLS via Orphanet