MCID: HLC001
MIFTS: 52

Holocarboxylase Synthetase Deficiency malady

Genetic diseases, Rare diseases, Skin diseases, Metabolic diseases categories

Aliases & Classifications for Holocarboxylase Synthetase Deficiency

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Sources:
45OMIM, 9Disease Ontology, 10diseasecard, 41NIH Rare Diseases, 21Genetics Home Reference, 11DISEASES, 43Novoseek, 47Orphanet, 60UMLS, 20GeneTests, 22GTR, 55SNOMED-CT, 33MeSH, 34MESH via Orphanet, 26ICD10 via Orphanet, 61UMLS via Orphanet
See all sources

Holocarboxylase Synthetase Deficiency, Aliases & Descriptions:

Name: Holocarboxylase Synthetase Deficiency 45 9 10 41 21 11 43 47 60
Holocarboxylase Synthetase 10 20 22
Multiple Carboxylase Deficiency 41 60
Early-Onset Biotin-Responsive Multiple Carboxylase Deficiency 21
Multiple Carboxylase Deficiency - Neonatal Onset 9
Multiple Carboxylase Deficiency, Neonatal Form 21
Early-Onset Multiple Carboxylase Deficiency 47
 
Early-Onset Combined Carboxylase Deficiency 21
Infantile Multiple Carboxylase Deficiency 21
Neonatal Multiple Carboxylase Deficiency 47
Macular Dystrophy, Corneal Type 1 60
Biotin- Ligase Deficiency 9
Hlcs Deficiency 21
Mcd 41


Classifications:

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


Characteristics (Orphanet epidemiological data):

47
holocarboxylase synthetase deficiency:
Inheritance: Autosomal recessive; Prevalence: 1-9/1000000 (Europe); Age of onset: Infancy,Neonatal; Age of death: any age


External Ids:

OMIM45 253270
Disease Ontology9 DOID:859
MeSH33 D028922
Orphanet47 79242
MESH via Orphanet34 D028922
ICD10 via Orphanet26 E53.8
UMLS via Orphanet61 C0268581

Summaries for Holocarboxylase Synthetase Deficiency

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OMIM:45 Early-onset multiple carboxylase deficiency, or holocarboxylase deficiency, is an autosomal recessive disorder of... (253270) more...

MalaCards based summary: Holocarboxylase Synthetase Deficiency, also known as holocarboxylase synthetase, is related to biotinidase deficiency and multiple carboxylase deficiency, and has symptoms including behavioral abnormality, seizures and muscular hypotonia. 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, eye and lung.

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

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.

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

Related Diseases for Holocarboxylase Synthetase Deficiency

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



Diseases related to holocarboxylase synthetase deficiency

Symptoms for Holocarboxylase Synthetase Deficiency

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Symptoms by clinical synopsis from OMIM:

253270

Clinical features from OMIM:

253270

Symptoms:

 47 (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

HPO human phenotypes related to Holocarboxylase Synthetase Deficiency:

(show all 33)
id Description Frequency HPO Source Accession
1 behavioral abnormality hallmark (90%) HP:0000708
2 seizures hallmark (90%) HP:0001250
3 muscular hypotonia hallmark (90%) HP:0001252
4 weight loss hallmark (90%) HP:0001824
5 nausea and vomiting hallmark (90%) HP:0002017
6 inflammatory abnormality of the eye hallmark (90%) HP:0100533
7 cheilitis hallmark (90%) HP:0100825
8 hyperammonemia typical (50%) HP:0001987
9 respiratory insufficiency typical (50%) HP:0002093
10 abnormal pattern of respiration typical (50%) HP:0002793
11 dry skin occasional (7.5%) HP:0000958
12 alopecia occasional (7.5%) HP:0001596
13 thrombocytopenia occasional (7.5%) HP:0001873
14 incoordination occasional (7.5%) HP:0002311
15 reduced consciousness/confusion occasional (7.5%) HP:0004372
16 autosomal recessive inheritance HP:0000007
17 irritability HP:0000737
18 skin rash HP:0000988
19 seizures HP:0001250
20 muscular hypotonia HP:0001252
21 lethargy HP:0001254
22 coma HP:0001259
23 global developmental delay HP:0001263
24 hypertonia HP:0001276
25 alopecia HP:0001596
26 thrombocytopenia HP:0001873
27 metabolic acidosis HP:0001942
28 hyperammonemia HP:0001987
29 organic aciduria HP:0001992
30 vomiting HP:0002013
31 tachypnea HP:0002789
32 hyperventilation HP:0002883
33 feeding difficulties in infancy HP:0008872

Drugs & Therapeutics for Holocarboxylase Synthetase Deficiency

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Drug clinical trials:

Search ClinicalTrials for Holocarboxylase Synthetase Deficiency

Search NIH Clinical Center for Holocarboxylase Synthetase Deficiency

Genetic Tests for Holocarboxylase Synthetase Deficiency

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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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MalaCards organs/tissues related to Holocarboxylase Synthetase Deficiency:

31
Skin, Eye, Lung

Animal Models for Holocarboxylase Synthetase Deficiency or affiliated genes

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Publications for Holocarboxylase Synthetase Deficiency

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Articles related to Holocarboxylase Synthetase Deficiency:

(show all 46)
idTitleAuthorsYear
1
Severe neonatal holocarboxylase synthetase deficiency in west african siblings. (25690727)
2015
2
Clinical Presentation and Positive Outcome of Two Siblings with Holocarboxylase Synthetase Deficiency Caused by a Homozygous L216R Mutation. (24085707)
2013
3
A novel molecular mechanism to explain biotin-unresponsive holocarboxylase synthetase deficiency. (21894551)
2012
4
The first reported HLCS gene mutation causing holocarboxylase synthetase deficiency in a Vietnamese patient. (21874615)
2012
5
Holocarboxylase synthetase deficiency: novel clinical and molecular findings. (20095979)
2010
6
A case of holocarboxylase synthetase deficiency with insufficient response to prenatal biotin therapy. (19201116)
2009
7
Positive newborn screen in the biochemically normal infant of a mother with treated holocarboxylase synthetase deficiency. (19357990)
2009
8
Management of a patient with holocarboxylase synthetase deficiency. (18974016)
2008
9
Microbial biotin protein ligases aid in understanding holocarboxylase synthetase deficiency. (18442489)
2008
10
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
11
Carnitine transporter and holocarboxylase synthetase deficiencies in The Faroe Islands. (17417720)
2007
12
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
13
Holocarboxylase synthetase deficiency presenting as ichthyosis. (16650223)
2006
14
Holocarboxylase synthetase deficiency: report of one case. (17407983)
2006
15
First prenatal molecular diagnosis in a family with holocarboxylase synthetase deficiency. (16231399)
2005
16
Severe holocarboxylase synthetase deficiency with incomplete biotin responsiveness resulting in antenatal insult in samoan neonates. (16027709)
2005
17
A genomic approach to mutation analysis of holocarboxylase synthetase gene in three Chinese patients with late-onset holocarboxylase synthetase deficiency. (12633764)
2003
18
Partial response to biotin therapy in a patient with holocarboxylase synthetase deficiency: clinical, biochemical, and molecular genetic aspects. (12855220)
2003
19
Clinical findings and biochemical and molecular analysis of four patients with holocarboxylase synthetase deficiency. (12124727)
2002
20
Structure of human holocarboxylase synthetase gene and mutation spectrum of holocarboxylase synthetase deficiency. (11735028)
2001
21
Holocarboxylase synthetase deficiency]. (11462701)
2001
22
Haplotype analysis suggests that the two predominant mutations in Japanese patients with holocarboxylase synthetase deficiency are founder mutations. (11185745)
2000
23
Diagnosis and molecular analysis of an atypical case of holocarboxylase synthetase deficiency. (10653324)
2000
24
Late-onset holocarboxylase synthetase deficiency with homologous R508W mutation. (10770035)
2000
25
Holocarboxylase synthetase deficiency: urinary metabolites masked by gross ketosis. (11196112)
2000
26
Holocarboxylase synthetase deficiency: report of a case with onset in late infancy. (10234606)
1999
27
Relationship between kinetic properties of mutant enzyme and biochemical and clinical responsiveness to biotin in holocarboxylase synthetase deficiency. (10590022)
1999
28
Identification and characterization of mutations in patients with holocarboxylase synthetase deficiency. (10190325)
1999
29
Prenatal diagnosis of holocarboxylase synthetase deficiency by assay of the enzyme in chorionic villus material followed by prenatal treatment. (10437643)
1999
30
Prenatal diagnosis and treatment of holocarboxylase synthetase deficiency. (10215065)
1999
31
Deficiency of biotinyl-AMP synthetase activity in fibroblasts of patients with holocarboxylase synthetase deficiency. (9758715)
1998
32
Holocarboxylase synthetase deficiency (early-onset multiple carboxylase deficiency)]. (9645047)
1998
33
Late-onset holocarboxylase synthetase-deficiency: pre- and post-natal diagnosis and evaluation of effectiveness of antenatal biotin therapy. (9686819)
1998
34
Molecular analysis of new Japanese patients with holocarboxylase synthetase deficiency. (9870216)
1998
35
Resolution of subependymal cysts in neonatal holocarboxylase synthetase deficiency. (9183268)
1997
36
Enzymatic diagnosis of holocarboxylase synthetase deficiency using apo-carboxyl carrier protein as a substrate. (8814349)
1996
37
Late-onset holocarboxylase synthetase deficiency. (8982946)
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 holocarboxylase synthetase deficiency. (3860175)
1985
44
Lactic acidosis in biotin-responsive multiple carboxylase deficiency caused by holocarboxylase synthetase deficiency of early and late onset. (6811711)
1982
45
Serum and urinary biotin levels during treatment of holocarboxylase synthetase deficiency. (7226522)
1981
46
Holocarboxylase synthetase deficiency: a biotin-responsive organic acidemia. (7365583)
1980

Variations for Holocarboxylase Synthetase Deficiency

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UniProtKB/Swiss-Prot 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_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:

6
id Gene Variation 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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Search GEO for disease gene expression data for Holocarboxylase Synthetase Deficiency.

Pathways for genes affiliated with Holocarboxylase Synthetase Deficiency

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Pathways related to Holocarboxylase Synthetase Deficiency according to GeneCards Suite gene sharing:

idSuper pathways (with members indented)ScoreTop Affiliating Genes
19.0BTD, HLCS
2
Show member pathways
flavin biosynthesis IV (mammalian)36
molybdenum cofactor biosynthesis36
coenzyme A biosynthesis36
thiamin salvage III36
alanine biosynthesis III36
thio-molybdenum cofactor biosynthesis36
biotin-carboxyl carrier protein assembly36
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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Sources:
43Novoseek, 24HMDB, 12DrugBank
See all sources

Compounds related to Holocarboxylase Synthetase Deficiency according to GeneCards Suite gene sharing:

(show all 14)
idCompoundScoreTop Affiliating Genes
1carnitine439.4HLCS, PC
2s-adenosylmethionine43 24 1211.4HLCS, PC
3acetyl-coa43 2410.3PC, HLCS
4alpha lipoic acid439.3PC, BTD
5multivitamin439.3BTD, HLCS
6pyruvate439.2PC, HLCS
7zinc43 2410.1BTD, PC
8glycogen43 249.8PC, BTD
93-methylcrotonyl-coa43 249.8HLCS, PC, BTD
10acyl-coa438.8BTD, HLCS, PC
11biotin43 24 1210.8PC, HLCS, BTD
12fatty acid438.7BTD, PC, HLCS
13lysine438.7BTD, PC, HLCS
14lactate438.7BTD, HLCS, PC

GO Terms for genes affiliated with Holocarboxylase Synthetase Deficiency

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Cellular components related to Holocarboxylase Synthetase Deficiency according to GeneCards Suite gene sharing:

idNameGO IDScoreTop Affiliating Genes
1mitochondrial matrixGO:00057599.1BTD, PC

Biological processes related to Holocarboxylase Synthetase Deficiency according to GeneCards Suite gene sharing:

idNameGO IDScoreTop Affiliating Genes
1biotin metabolic processGO:00067688.5BTD, HLCS, PC
2small molecule metabolic processGO:00442818.5BTD, PC, HLCS
3water-soluble vitamin metabolic processGO:00067678.4BTD, PC, HLCS
4vitamin metabolic processGO:00067668.2BTD, HLCS, PC

Molecular functions related to Holocarboxylase Synthetase Deficiency according to GeneCards Suite gene sharing:

idNameGO IDScoreTop Affiliating Genes
1biotin carboxylase activityGO:00040759.1BTD, PC
2biotin bindingGO:00093749.0PC, HLCS

Products for genes affiliated with Holocarboxylase Synthetase Deficiency

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  • Antibodies
  • Proteins
  • Lysates
  • Antibodies
  • Proteins
  • Kits and Assays

Sources for Holocarboxylase Synthetase Deficiency

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3CDC
13ExPASy
14FMA
22GTR
23HGMD
24HMDB
25ICD10
26ICD10 via Orphanet
27ICD9CM
28IUPHAR
29KEGG
33MeSH
34MESH via Orphanet
35MGI
38NCIt
39NDF-RT
42NINDS
43Novoseek
45OMIM
46OMIM via Orphanet
50PubMed
51QIAGEN
56SNOMED-CT via Orphanet
60UMLS
61UMLS via Orphanet