MCID: HLC001
MIFTS: 47

Holocarboxylase Synthetase Deficiency malady

Skin, Metabolic, Ear categories

Summaries for Holocarboxylase Synthetase Deficiency

Sources:
8Disease Ontology, 21Genetics Home Reference, 64Wikipedia, 47OMIM, 33MalaCards
See all sources

Fully expand this MalaCard

Export this MalaCard
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 biotin deficiency, and has symptoms including chronic uveitis/blepharitis/episcleritis/scleritis/conjonctivitis/keratitis, oral mucosa disease/cheilitis and nausea/vomiting/regurgitation/merycism/hyperemesis. 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.

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

Wikipedia:64 Holocarboxylase synthetase deficiency is an inherited metabolic disorder in which the body is unable to... more...

Description from OMIM:47 253270

Aliases & Classifications for Holocarboxylase Synthetase Deficiency

Sources:
8Disease Ontology, 9diseasecard, 43NIH Rare Diseases, 21Genetics Home Reference, 47OMIM, 10DISEASES, 45Novoseek, 49Orphanet, 61UMLS, 20GeneTests, 22GTR, 57SNOMED-CT, 35MeSH, 26ICD10 via Orphanet
See all sources

Classifications:

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


Characteristics (Orphanet epidemiological data):

49
holocarboxylase synthetase deficiency:
Inheritance: Autosomal recessive; Age of onset: Neonatal/infancy; Age of death: Any age


Aliases & Descriptions:

holocarboxylase synthetase deficiency 8 9 43 21 47 10 45 49 61
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 49
infantile multiple carboxylase deficiency 21
neonatal multiple carboxylase deficiency 49
biotin- ligase deficiency 8
hlcs deficiency 21


External Ids:

Disease Ontology8 DOID:859
MeSH35 D028922
OMIM47 253270
ICD10 via Orphanet26 E53.8

Related Diseases for Holocarboxylase Synthetase Deficiency

Sources:
17GeneCards, 18GeneDecks
See all sources

Graphical network of the top 20 diseases related to Holocarboxylase Synthetase Deficiency:



Diseases related to holocarboxylase synthetase deficiency

Clinical Features for Holocarboxylase Synthetase Deficiency

Sources:
47OMIM, 49Orphanet
See all sources

Clinical features from OMIM:

253270

Clinical synopsis from OMIM:

253270

Symptoms:

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

Drugs & Therapeutics for Holocarboxylase Synthetase Deficiency

Sources:
5CenterWatch, 42NIH Clinical Center, 6ClinicalTrials, 61UMLS, 41NDF-RT
See all sources

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

Sources:
20GeneTests, 22GTR
See all sources

Genetic tests related to Holocarboxylase Synthetase Deficiency:

id Genetic test Affiliating Genes
1 Holocarboxylase Synthetase Deficiency20 22 HLCS

Anatomical Context for Holocarboxylase Synthetase Deficiency

Animal Models for Holocarboxylase Synthetase Deficiency or affiliated genes

Sources:
28inGenious Targeting Laboratory
See all sources

Publications for Holocarboxylase Synthetase Deficiency

Sources:
51PubMed
See all sources

Articles related to Holocarboxylase Synthetase Deficiency:

(show top 50)    (show all 52)
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
Holocarboxylase synthetase deficiency: novel clinical and molecular findings. (20095979)
2010
4
A case of holocarboxylase synthetase deficiency with insufficient response to prenatal biotin therapy. (19201116)
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
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
10
Holocarboxylase synthetase deficiency presenting as ichthyosis. (16650223)
2006
11
Holocarboxylase synthetase deficiency: report of one case. (17407983)
2006
12
First prenatal molecular diagnosis in a family with holocarboxylase synthetase deficiency. (16231399)
2005
13
Severe holocarboxylase synthetase deficiency with incomplete biotin responsiveness resulting in antenatal insult in samoan neonates. (16027709)
2005
14
Reduced histone biotinylation in multiple carboxylase deficiency patients: a nuclear role for holocarboxylase synthetase. (14613969)
2004
15
A genomic approach to mutation analysis of holocarboxylase synthetase gene in three Chinese patients with late-onset holocarboxylase synthetase deficiency. (12633764)
2003
16
Partial response to biotin therapy in a patient with holocarboxylase synthetase deficiency: clinical, biochemical, and molecular genetic aspects. (12855220)
2003
17
Clinical findings and biochemical and molecular analysis of four patients with holocarboxylase synthetase deficiency. (12124727)
2002
18
Structure of human holocarboxylase synthetase gene and mutation spectrum of holocarboxylase synthetase deficiency. (11735028)
2001
19
Holocarboxylase synthetase deficiency]. (11462701)
2001
20
Haplotype analysis suggests that the two predominant mutations in Japanese patients with holocarboxylase synthetase deficiency are founder mutations. (11185745)
2000
21
Diagnosis and molecular analysis of an atypical case of holocarboxylase synthetase deficiency. (10653324)
2000
22
Late-onset holocarboxylase synthetase deficiency with homologous R508W mutation. (10770035)
2000
23
Holocarboxylase synthetase deficiency: urinary metabolites masked by gross ketosis. (11196112)
2000
24
Holocarboxylase synthetase deficiency: report of a case with onset in late infancy. (10234606)
1999
25
Relationship between kinetic properties of mutant enzyme and biochemical and clinical responsiveness to biotin in holocarboxylase synthetase deficiency. (10590022)
1999
26
Identification and characterization of mutations in patients with holocarboxylase synthetase deficiency. (10190325)
1999
27
Prenatal diagnosis of holocarboxylase synthetase deficiency by assay of the enzyme in chorionic villus material followed by prenatal treatment. (10437643)
1999
28
Prenatal diagnosis and treatment of holocarboxylase synthetase deficiency. (10215065)
1999
29
Deficiency of biotinyl-AMP synthetase activity in fibroblasts of patients with holocarboxylase synthetase deficiency. (9758715)
1998
30
Holocarboxylase synthetase deficiency (early-onset multiple carboxylase deficiency)]. (9645047)
1998
31
Late-onset holocarboxylase synthetase-deficiency: pre- and post-natal diagnosis and evaluation of effectiveness of antenatal biotin therapy. (9686819)
1998
32
Molecular analysis of new Japanese patients with holocarboxylase synthetase deficiency. (9870216)
1998
33
Characterization of mutant holocarboxylase synthetase (HCS): a Km for biotin was not elevated in a patient with HCS deficiency. (9396568)
1997
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
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

Sources:
63UniProtKB/Swiss-Prot
See all sources

Genetic disease variations for Holocarboxylase Synthetase Deficiency:

63 (show all 21)
id Symbol AA change Variation 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

Sources:
1BioGPS, 15Gene Expression Omnibus DataSets
See all sources
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

Sources:
30KEGG, 54Reactome, 38NCBI BioSystems Database
See all sources

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

Sources:
45Novoseek, 50PharmGKB, 11DrugBank, 24HMDB
See all sources

Compounds related to Holocarboxylase Synthetase Deficiency according to GeneCards/GeneDecks:

(show all 13)
idCompoundScoreTop Affiliating Genes
1multivitamin459.5BTD, HLCS
2valproic acid45 50 11 2412.3SLC22A5, BTD
3pyruvate459.1PC, HLCS
4alpha lipoic acid459.1BTD, PC
5s-adenosylmethionine45 11 2411.0PC, HLCS
6carnitine458.9SLC22A5, PC, HLCS
7acetyl-coa45 249.8PC, HLCS
83-methylcrotonyl-coa45 249.8PC, BTD, HLCS
9acyl-coa458.8HLCS, BTD, PC
10biotin45 11 2410.7PC, BTD, HLCS
11fatty acid458.7HLCS, BTD, PC
12lysine458.7PC, BTD, HLCS
13lactate458.6PC, BTD, HLCS

GO Terms for genes affiliated with Holocarboxylase Synthetase Deficiency

Sources:
16Gene Ontology
See all sources

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

  • Antibodies
  • Proteins
  • Lysates
  • Antibodies

Sources for Holocarboxylase Synthetase Deficiency

3CDC
13ExPASy
14FMA
22GTR
23HGMD
24HMDB
25ICD10
26ICD10 via Orphanet
27ICD9CM
29IUPHAR
30KEGG
35MeSH
36MESH via Orphanet
37MGI
40NCIt
41NDF-RT
44NINDS
45Novoseek
47OMIM
48OMIM via Orphanet
51PubMed
52QIAGEN
58SNOMED-CT via Orphanet
61UMLS
62UMLS via Orphanet