MCID: SVR003
MIFTS: 59

Severe Congenital Neutropenia malady

Blood diseases category

Summaries for Severe Congenital Neutropenia

About this section
Sources:
21Genetics Home Reference, 46OMIM, 32MalaCards
See all sources

Fully expand this MalaCard

Export this MalaCard
Genetics Home Reference:21 Severe congenital neutropenia is a condition that causes affected individuals to be prone to recurrent infections. People with this condition have a shortage (deficiency) of neutrophils, a type of white blood cell that plays a role in inflammation and in fighting infection. The deficiency of neutrophils, called neutropenia, is apparent at birth or soon afterward. It leads to recurrent infections beginning in infancy, including infections of the sinuses, lungs, and liver. Affected individuals can also develop fevers and inflammation of the gums (gingivitis) and skin. Approximately 40 percent of affected people have decreased bone density (osteopenia) and may develop osteoporosis, a condition that makes bones progressively more brittle and prone to fracture. In people with severe congenital neutropenia, these bone disorders can begin at any time from infancy through adulthood.

MalaCards: Severe Congenital Neutropenia, also known as severe infantile genetic neutropenia, is related to neutropenia and leukemia. An important gene associated with Severe Congenital Neutropenia is G6PC3 (glucose 6 phosphatase, catalytic, 3), and among its related pathways are PECAM1 interactions and Hematopoietic cell lineage. The compounds nadph and valine have been mentioned in the context of this disorder. Affiliated tissues include bone, liver and lung, and related mouse phenotypes are digestive/alimentary and skeleton.

Description from OMIM:46 300299,612541,610738,202700,613107

Aliases & Classifications for Severe Congenital Neutropenia

About this section
Sources:
8Disease Ontology, 20GeneTests, 21Genetics Home Reference, 10DISEASES, 48Orphanet, 30LifeMap Discovery™, 60UMLS, 44Novoseek, 46OMIM, 35MESH via Orphanet, 26ICD10 via Orphanet, 57SNOMED-CT via Orphanet, 61UMLS via Orphanet
See all sources

Classifications:

Malacards categories (disease lists): (See all malacards categories)
Anatomical: Blood diseases


Characteristics (Orphanet epidemiological data):

48
severe congenital neutropenia:
Inheritance: Autosomal dominant,Autosomal recessive,X-linked recessive; Prevalence: 1-9/1000000; Age of onset: Childhood; Age of death: Any age


Aliases & Descriptions:

severe congenital neutropenia 8 20 21 10 48 30 60
severe infantile genetic neutropenia 21
infantile genetic agranulocytosis 21
neutropenia, severe congenital 44
kostmann's agranulocytosis 21
congenital agranulocytosis 21
congenital neutropenia 21
kostmann's syndrome 21
kostmanns syndrome 44
kostmann disease 21


External Ids:

Disease Ontology8 DOID:0050590
MESH via Orphanet35 C537592
ICD10 via Orphanet26 D70
SNOMED-CT via Orphanet57 89655007
UMLS via Orphanet61 C1853118

Related Diseases for Severe Congenital Neutropenia

About this section
Sources:
17GeneCards, 18GeneDecks
See all sources

Diseases in the Severe Congenital Neutropenia family:

Neutropenia Elane-Related Neutropenia
Neutropenia Chronic Familial Gata1-Related Neutropenia

Diseases related to Severe Congenital Neutropenia via text searches within MalaCards or GeneCards/GeneDecks gene sharing:

(show top 50)    (show all 78)
idRelated DiseaseScoreTop Affiliating Genes
1neutropenia31.8ELANE, CSF3R, CSF3, WAS, HAX1, G6PC3
2leukemia31.0CSF3R, CSF3, CISH, INPP5D, FPR1, LEF1
3acute leukemia30.9CSF3R, CSF3, INPP5D, FCGR1A, PTPN6
4severe congenital neutropenia autosomal recessive 330.7ELANE, CSF3, CSF3R
5myeloid leukemia30.7CSF3R, CSF3, INPP5D, FPR1, PTPN6, ELANE
6periodontal disease30.1ELANE
7acute myeloid leukemia10.5
8severe congenital neutropenia x-linked10.4
9severe congenital neutropenia, autosomal recessive, 410.4
10neutropenia, severe congenital 1, autosomal dominant10.4
11osteoporosis10.4
12lymphoblastic leukemia10.4
13periodontitis10.4
14severe congenital neutropenia autosomal dominant10.4
15severe congenital neutropenia, autosomal dominant, 210.3
16wiskott-aldrich syndrome10.1
17acute monocytic leukemia10.1
18chronic granulomatous disease10.1
19rapidly progressive glomerulonephritis10.1
20leukocyte adhesion deficiency10.1
21liver inflammatory pseudotumor10.1
22orchitis10.1
23autosomal recessive disease10.1
24congenital nervous system abnormality10.1
25epididymo-orchitis10.1
26glomerulonephritis10.1
27hepatitis10.1
28laryngitis10.1
29leukocyte disease10.1
30monocytic leukemia10.1
31ovarian disease10.1
32pneumonia10.1
33vasculitis10.1
34sickle cell disease10.1
35recurrent fever multi-gene panels10.1
36neutropenia, severe congenital, 5, autosomal recessive10.1
37gas gangrene10.0
38reticular dysgenesis10.0
39gingivitis10.0
40multiple myeloma10.0CSF3
41pancreatitis10.0ELANE
42myelodysplastic syndromes10.0CSF3R, CSF3
43stomach cancer10.0RAC2
44adult respiratory distress syndrome10.0C5AR1
45capillary leak syndrome10.0ELANE
46hepatocellular carcinoma10.0ELANE, CISH
47arthus reaction10.0ELANE
48measles10.0PTPN6
49cyclic hematopoiesis10.0ELANE, CSF3
50myeloma10.0CSF3, INPP5D, FCGR1A

Graphical network of the top 20 diseases related to Severe Congenital Neutropenia:



Diseases related to severe congenital neutropenia

Clinical Features for Severe Congenital Neutropenia

About this section
Sources:
46OMIM
See all sources

Clinical features from OMIM:

300299,612541,610738,202700,613107

Drugs & Therapeutics for Severe Congenital Neutropenia

About this section
Sources:
5CenterWatch, 41NIH Clinical Center, 6ClinicalTrials, 30LifeMap Discovery™, 60UMLS, 40NDF-RT
See all sources

Approved drugs:

Search CenterWatch for Severe Congenital Neutropenia

Drug clinical trials:

Search ClinicalTrials for Severe Congenital Neutropenia

Search NIH Clinical Center for Severe Congenital Neutropenia

Search CenterWatch for Severe Congenital Neutropenia

Cell-based therapeutics:


LifeMap Discovery
The database of embryonic development, stem cell research and regenerative medicine
Read about Severe Congenital Neutropenia cell therapies at LifeMap Discovery.

Genetic Tests for Severe Congenital Neutropenia

About this section
Sources:
20GeneTests
See all sources

Genetic tests related to Severe Congenital Neutropenia:

id Genetic test Affiliating Genes
1 Severe Congenital Neutropenia20

Anatomical Context for Severe Congenital Neutropenia

About this section
Sources:
32MalaCards
See all sources

MalaCards organs/tissues related to Severe Congenital Neutropenia:

32
Bone, Liver, Lung, Skin, Myeloid, Bone marrow, Monocytes, T cells

Animal Models for Severe Congenital Neutropenia or affiliated genes

About this section
Sources:
36MGI
See all sources

MGI Mouse Phenotypes related to Severe Congenital Neutropenia:

36
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053819.8CEBPE, PTPN6, FPR1, INPP5D, NR0B2, WAS
2MP:00053909.7WAS, HAX1, INPP5D, LEF1, FCGR1A, C5AR1
3MP:00053799.6WAS, NR0B2, FPR1, LEF1, PTPN6
4MP:00053849.3CSF3R, WAS, HAX1, ARHGDIB, INPP5D, FPR1
5MP:00053769.2NR0B2, ARHGDIB, G6PC3, WAS, INPP5D, RAC2
6MP:00107689.1CAMP, HAX1, G6PC3, ARHGDIB, INPP5D, FPR1
7MP:00053978.9ARHGDIB, G6PC3, HAX1, WAS, CSF3, CSF3R
8MP:00053878.6ELANE, CAMP, CSF3R, CSF3, WAS, HAX1

Publications for Severe Congenital Neutropenia

About this section
Sources:
50PubMed
See all sources

Articles related to Severe Congenital Neutropenia:

(show top 50)    (show all 218)
idTitleAuthorsYear
1
A novel G6PC3 gene mutation in a patient with severe congenital neutropenia. (23018568)
2013
2
Prevalence of a new auto-activating colony stimulating factor 3 receptor mutation (CSF3R-T595I) in acute myeloid leukemia and severe congenital neutropenia. (23508011)
2013
3
Granulocyte colony-stimulating factor receptor signaling: implications for G-CSF responses and leukemic progression in severe congenital neutropenia. (23351988)
2013
4
Successful haploidentical PBSCT with subsequent T-cell addbacks in a boy with HyperIgM syndrome presenting as severe congenital neutropenia. (22928961)
2013
5
Genetics and pathophysiology of severe congenital neutropenia syndromes unrelated to neutrophil elastase. (23351987)
2013
6
A novel homozygous mutation in G6PC3 presenting as cyclic neutropenia and severe congenital neutropenia in the same family. (24105461)
2013
7
Sequential gain of mutations in severe congenital neutropenia progressing to acute myeloid leukemia. (22371884)
2012
8
Heterozygous M1V variant of ELA-2 gene mutation associated with G-CSF refractory severe congenital neutropenia. (21618407)
2011
9
Genetic etiologies of severe congenital neutropenia. (21206270)
2011
10
Cyclic neutropenia and severe congenital neutropenia in patients with a shared ELANE mutation and paternal haplotype: evidence for phenotype determination by modifying genes. (20582973)
2010
11
Resolving a genetic paradox throughout preimplantation genetic diagnosis for autosomal dominant severe congenital neutropenia. (20049848)
2010
12
Severe congenital neutropenia resulting from G6PC3 deficiency with increased neutrophil CXCR4 expression and myelokathexis. (20616219)
2010
13
The importance of dental care for a child with severe congenital neutropenia: a case report. (21044107)
2010
14
Digenic mutations in severe congenital neutropenia. (20220065)
2010
15
HAX1 mutation in an infant with severe congenital neutropenia. (20402072)
2010
16
Clinical implications of ELA2-, HAX1-, and G-CSF-receptor (CSF3R) mutations in severe congenital neutropenia. (19120359)
2009
17
Novel genetic etiologies of severe congenital neutropenia. (19782549)
2009
18
Neurological findings in severe congenital neutropenia with HAX1 mutations]. (19928538)
2009
19
Genetic and molecular diagnosis of severe congenital neutropenia. (19057199)
2009
20
A novel missense mutation in the HAX1 gene in severe congenital neutropenia patients (Kostmann disease). (19796188)
2009
21
Severe congenital neutropenia in 2 siblings of consanguineous parents. The role of HAX1 deficiency. (20128427)
2009
22
Severe congenital neutropenia and pegfilgrastim. (18774955)
2009
23
A novel mutation Ala57Val of the ELA2 gene in a Korean boy with severe congenital neutropenia. (18946670)
2009
24
Unrelated cord blood transplantation in children with severe congenital neutropenia. (18992063)
2009
25
Severe congenital neutropenia and the unfolded protein response. (18043239)
2008
26
Chronic idiopathic neutropenias and severe congenital neutropenia. (18043240)
2008
27
Severe congenital neutropenia: new genes explain an old disease. (17917547)
2007
28
Mutations of the ELA2 gene found in patients with severe congenital neutropenia induce the unfolded protein response and cellular apoptosis. (17761833)
2007
29
Neutrophil elastase in cyclic and severe congenital neutropenia. (17053055)
2007
30
Genetic heterogeneity in severe congenital neutropenia: how many aberrant pathways can kill a neutrophil? (17989524)
2007
31
Strong evidence for autosomal dominant inheritance of severe congenital neutropenia associated with ELA2 mutations. (16737875)
2006
32
Malignant myeloid transformation in a child with severe congenital neutropenia (Kostmann's syndrome). (16898320)
2006
33
A comparison of the defective granulopoiesis in childhood cyclic neutropenia and in severe congenital neutropenia. (16079102)
2005
34
Hematopoietic stem cell transplantation in severe congenital neutropenia: experience of the French SCN register. (15489867)
2005
35
Umbilical cord blood stem cell transplantation from unrelated HLA-matched donor in an infant with severe congenital neutropenia. (15004540)
2004
36
Familial severe congenital neutropenia associated with infantile osteoporosis: a new entity. (12508266)
2003
37
Paternal mosaicism proves the pathogenic nature of mutations in neutrophil elastase in severe congenital neutropenia. (12091371)
2002
38
Mutant elastase in pathogenesis of cyclic and severe congenital neutropenia. (12468929)
2002
39
Spontaneous remission of granulocyte colony-stimulating factor-associated leukemia in a child with severe congenital neutropenia. (11071667)
2000
40
Granulocyte colony-stimulating factor receptor mutations in severe congenital neutropenia transforming to acute myelogenous leukemia confer resistance to apoptosis and enhance cell survival. (10706885)
2000
41
Defective internalization and sustained activation of truncated granulocyte colony-stimulating factor receptor found in severe congenital neutropenia/acute myeloid leukemia. (9885206)
1999
42
Structural abnormalities in the G-CSF receptor in severe congenital neutropenia. (10634179)
1999
43
Mutations of the granulocyte-colony stimulating factor receptor in patients with severe congenital neutropenia are not required for transformation to acute myeloid leukaemia and may be a bystander phenomenon. (9576194)
1998
44
Lack of alterations in the cytoplasmic domains of the granulocyte colony-stimulating factor receptors in eight cases of severe congenital neutropenia. (7833487)
1995
45
Mutations in the gene for the granulocyte colony-stimulating-factor receptor in patients with acute myeloid leukemia preceded by severe congenital neutropenia. (7542747)
1995
46
Osteoporosis in severe congenital neutropenia treated with granulocyte colony-stimulating factor. (7539627)
1995
47
Severe congenital neutropenia unresponsive to G-CSF. (7577650)
1995
48
Severe congenital neutropenia: clinical effects and neutrophil function during treatment with granulocyte colony-stimulating factor. (1707086)
1991
49
Differential effects of granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor in children with severe congenital neutropenia. (1689595)
1990
50
Granulopoiesis in severe congenital neutropenia. (1083263)
1976

Genetic Variations for Severe Congenital Neutropenia

About this section

Expression for genes affiliated with Severe Congenital Neutropenia

About this section
Sources:
1BioGPS, 15Gene Expression Omnibus DataSets
See all sources
Expression patterns in normal tissues for genes affiliated with Severe Congenital Neutropenia

Search GEO for disease gene expression data for Severe Congenital Neutropenia.

Pathways for genes affiliated with Severe Congenital Neutropenia

About this section
Sources:
53Reactome, 29KEGG, 12EMD Millipore, 37NCBI BioSystems Database, 51QIAGEN
See all sources

Pathways related to Severe Congenital Neutropenia according to GeneCards/GeneDecks:

(show all 13)
idSuper pathways (with members indented)ScoreTop Affiliating Genes
110.2PTPN6, INPP5D
210.1CSF3R, CSF3, FCGR1A
3
Immune response IL-2 activation and signaling pathway
Hide members
10.1CISH, INPP5D, PTPN6
4
Hide members
10.1PTPN6, INPP5D, CISH
510.0CSF3R, CSF3, CISH, PTPN6
610.0WAS, LEF1, RAC2, PTPN6
710.0FPR1, FCGR1A, FCGR3A, C5AR1
8
Hide members
10.0PTPN6, FCGR1A, INPP5D, CISH
9
Hide members
10.0PTPN6, RAC2, INPP5D, WAS
1010.0PTPN6, RAC2, INPP5D, CISH
119.9FCGR3A, FCGR1A, RAC2, INPP5D, WAS
12
Hide members
9.9WAS, INPP5D, RAC2, FCGR3A, PTPN6
13
Hide members
9.8CSF3R, CSF3, WAS, LEF1, RAC2, PTPN6

Compounds for genes affiliated with Severe Congenital Neutropenia

About this section
Sources:
44Novoseek, 24HMDB, 11DrugBank, 49PharmGKB, 59Tocris Bioscience, 28IUPHAR, 2BitterDB
See all sources

Compounds related to Severe Congenital Neutropenia according to GeneCards/GeneDecks:

(show top 50)    (show all 59)
idCompoundScoreTop Affiliating Genes
1nadph44 2411.7PTPN6, RAC2
2valine4410.6PTPN6, ELANE
3pegfilgrastim44 1111.6CSF3R, CSF3, ELANE
4filgrastim44 1111.6CSF3R, CSF3, ELANE
5nitroblue tetrazolium4410.5CSF3R, CSF3, FCGR1A
6gemtuzumab ozogamicin44 1111.5CSF3, FCGR1A, FCGR3A
7alemtuzumab44 1111.5CSF3, FCGR1A, FCGR3A
8Palivizumab1110.5FCGR3A, FCGR1A
9anaphylatoxin4410.5ELANE, C5AR1, FPR1
10Intravenous Immunoglobulin1110.5FCGR3A, FCGR1A
11pentoxifylline44 1111.5CAMP, FPR1, ELANE
12cytochalasin b4410.5ELANE, C5AR1, FPR1
13Ibritumomab1110.4FCGR1A, FCGR3A
14bevacizumab49 1111.4FCGR1A, FCGR3A
15gp 1304410.4PTPN6, CISH, CSF3, CSF3R
16cytochalasin d44 5911.4CAMP, WAS, FCGR1A, PTPN6
17dexamethasone44 49 28 1113.4CAMP, CISH, FPR1, FCGR1A
18rituximab44 49 1112.4FCGR3A, FCGR1A, CSF3
19tositumomab49 1111.4FCGR1A, FCGR3A
20dbc-amp4410.4CAMP, FPR1, C5AR1
21n-formylmethionyl-leucylphenylalanine4410.3CSF3, FPR1, RAC2, C5AR1, ELANE
22alefacept44 1111.3FCGR1A, FCGR3A
23genistein44 28 59 2 11 2415.3PTPN6, FCGR1A, FPR1, CSF3R, CAMP
24fibrinogen4410.3ELANE, C5AR1, PTPN6, FCGR1A, FPR1
25phosphotyrosine4410.3CSF3R, CISH, INPP5D, FCGR3A, PTPN6
26phenylalanine4410.3CSF3R, INPP5D, FCGR3A, PTPN6, C5AR1
27arachidonic acid44 28 11 2413.2CAMP, FPR1, RAC2, FCGR1A, C5AR1
28wortmannin4410.2CAMP, WAS, INPP5D, FPR1, C5AR1
29endotoxin4410.2CAMP, CSF3R, CSF3, FPR1, C5AR1, ELANE
30pge24410.2ELANE, C5AR1, FCGR1A, FPR1, CAMP
31gtp44 2811.2C5AR1, RAC2, FPR1, ARHGDIB, WAS
32heparin44 28 11 2413.2CAMP, CSF3R, FPR1, C5AR1, ELANE
33thymidine44 2411.2PTPN6, INPP5D, CSF3, CSF3R, CAMP
34phosphoinositide4410.1CISH, INPP5D, FPR1, RAC2, PTPN6, C5AR1
35vegf4410.1CAMP, CSF3R, CSF3, FPR1, PTPN6, C5AR1
36asparagine4410.1C5AR1, FCGR3A, RAC2
37oxygen44 2411.1CSF3R, FPR1, RAC2, FCGR1A, FCGR3A, C5AR1
38retinoic acid44 2411.0CAMP, CSF3R, CSF3, FPR1, PTPN6, ELANE
39leukotriene b444 59 2412.0ELANE, C5AR1, FPR1
40oligonucleotide4410.0CAMP, CSF3R, CISH, FPR1, GFI1, FCGR1A
41h2o24410.0ELANE, C5AR1, PTPN6, FCGR1A, FPR1
42superoxide44 2411.0CSF3R, CSF3, FPR1, RAC2, FCGR1A, PTPN6
43histamine44 28 2412.0C5AR1, FPR1, INPP5D, CAMP
44fmlp449.9ELANE, CAMP, CSF3R, CSF3, FPR1, RAC2
45phosphatidylinositol449.8CSF3R, WAS, CISH, INPP5D, FPR1, RAC2
46lipid449.7NR0B2, CISH, WAS, CAMP, INPP5D, FPR1
47phospholipid449.6CAMP, INPP5D, PTPN6, C5AR1
48serine449.6CAMP, CSF3R, WAS, CISH, INPP5D, FPR1
49calcium44 49 11 2412.5NR0B2, CISH, WAS, CSF3R, CAMP, INPP5D
50tyrosine449.1CISH, ARHGDIB, WAS, CSF3, CSF3R, CAMP

GO Terms for genes affiliated with Severe Congenital Neutropenia

About this section
Sources:
16Gene Ontology
See all sources

Biological processes related to Severe Congenital Neutropenia according to GeneCards/GeneDecks:

(show all 11)
idNameGO IDScoreTop Affiliating Genes
1positive regulation of granulocyte differentiationGO:03085410.4LEF1, HAX1
2defense responseGO:00695210.4CEBPE, WAS, CSF3R
3cellular response to cytokine stimulusGO:07134510.3LEF1, HAX1, CSF3
4positive regulation of phosphatidylinositol 3-kinase cascadeGO:01406810.3CSF3, HAX1, PTPN6
5cellular response to lipopolysaccharideGO:07122210.3CSF3, GFI1, CEBPE
6positive regulation of actin cytoskeleton reorganizationGO:200025110.3CSF3, HAX1
7negative regulation of signal transductionGO:00996810.2INPP5D, CISH
8Fc-gamma receptor signaling pathway involved in phagocytosisGO:03809610.0FCGR3A, FCGR1A, WAS
9immune responseGO:00695510.0C5AR1, CSF3, WAS, ARHGDIB, FCGR1A, FCGR3A
10signal transductionGO:0071659.8C5AR1, FCGR1A, RAC2, FPR1, INPP5D, CSF3R
11leukocyte migrationGO:0509009.8ELANE, PTPN6, INPP5D

Molecular functions related to Severe Congenital Neutropenia according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1IgG bindingGO:01986410.2FCGR3A, FCGR1A
2N-formyl peptide receptor activityGO:0049829.9C5AR1, FPR1
3protein bindingGO:0055159.0ELANE, CAMP, CSF3R, WAS, HAX1, CISH

Products for genes affiliated with Severe Congenital Neutropenia

About this section
  • Antibodies
  • Proteins
  • Lysates
  • Antibodies

Sources for Severe Congenital Neutropenia

About this section
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