MCID: SVR003
MIFTS: 59

Severe Congenital Neutropenia malady

Blood diseases category

Summaries for Severe Congenital Neutropenia

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21Genetics Home Reference, 46OMIM, 32MalaCards
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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

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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
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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

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Sources:
17GeneCards, 18GeneDecks
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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

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46OMIM
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Clinical features from OMIM:

300299,612541,610738,202700,613107

Drugs & Therapeutics for Severe Congenital Neutropenia

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5CenterWatch, 41NIH Clinical Center, 6ClinicalTrials, 30LifeMap Discovery™, 60UMLS, 40NDF-RT
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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

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20GeneTests
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Genetic tests related to Severe Congenital Neutropenia:

id Genetic test Affiliating Genes
1 Severe Congenital Neutropenia20

Anatomical Context for Severe Congenital Neutropenia

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32MalaCards
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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

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36MGI
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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

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50PubMed
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Articles related to Severe Congenital Neutropenia:

(show top 50)    (show all 218)
idTitleAuthorsYear
1
Severe congenital neutropenia in two siblings related to HAX1 mutation without neurodevelopmental disorders. (24341138)
2013
2
Ovarian failure in HAX1-deficient patients: is there a gender-specific difference in pubertal development in severe congenital neutropenia or Kostmann disease? (23050867)
2013
3
Pro-B acute lymphoblastic leukemia in a patient with severe congenital neutropenia: an unusual form of malignant evolution. (23391142)
2013
4
Resolution of Inflammatory Colitis With Pegfilgrastim Treatment in a Case of Severe Congenital Neutropenia Due to Glucose 6 Phosphatase Catalytic Subunit-3 Deficiency. (24322501)
2013
5
Prevention and control of infections in patients with severe congenital neutropenia; a follow up study. (22427476)
2012
6
Hepatic hemangioendothelioma in an infant with severe congenital neutropenia. (22510773)
2012
7
Incidence of severe congenital neutropenia in Sweden and risk of evolution to myelodysplastic syndrome/leukaemia. (22624626)
2012
8
Genetic defects in severe congenital neutropenia: emerging insights into life and death of human neutrophil granulocytes. (21219176)
2011
9
Novel ELANE gene mutation in a Korean girl with severe congenital neutropenia. (22148006)
2011
10
Cardiac and renal malformations in a patient with sepsis and severe congenital neutropenia. (23056709)
2010
11
Indications for hematopoietic cell transplantation for children with severe congenital neutropenia. (20819181)
2010
12
RAS and CSF3R mutations in severe congenital neutropenia. (19833857)
2009
13
Homozygous HAX1 mutations in severe congenital neutropenia patients with sporadic disease: a novel mutation in two unrelated British kindreds. (19036076)
2009
14
Compound heterozygous HAX1 mutations in a Swedish patient with severe congenital neutropenia and no neurodevelopmental abnormalities. (19499579)
2009
15
Severe congenital neutropenia: a negative synergistic effect of multiple mutations of ELANE (ELA2) gene. (19594744)
2009
16
Acute lymphoblastic leukemia following severe congenital neutropenia or de novo ALL? (19398129)
2009
17
Neutrophil elastase is severely down-regulated in severe congenital neutropenia independent of ELA2 or HAX1 mutations but dependent on LEF-1. (19620402)
2009
18
Unrelated cord blood transplantation for severe congenital neutropenia: report of two cases with very different transplant courses. (18433408)
2008
19
Lymphadenopathy as the primary manifestation of malignant transformation in two patients with severe congenital neutropenia. (18213714)
2008
20
Neutrophil elastase mutations and risk of leukaemia in severe congenital neutropenia. (18028488)
2008
21
Neurodevelopmental abnormalities associated with severe congenital neutropenia due to the R86X mutation in the HAX1 gene. (18611981)
2008
22
Non-myeloablative transplantation for severe congenital neutropenia. (17635003)
2008
23
Incidence of CSF3R mutations in severe congenital neutropenia and relevance for leukemogenesis: Results of a long-term survey. (16985178)
2007
24
HAX1 deficiency causes autosomal recessive severe congenital neutropenia (Kostmann disease). (17187068)
2007
25
Assignment of the gene locus for severe congenital neutropenia to chromosome 1q22 in the original Kostmann family from Northern Sweden. (17188649)
2007
26
Kostmann syndrome or infantile genetic agranulocytosis, part one: celebrating 50 years of clinical and basic research on severe congenital neutropenia. (17129957)
2006
27
Neutrophil elastase and granulocyte colony-stimulating factor receptor mutation analyses and leukemia evolution in severe congenital neutropenia patients belonging to the original Kostmann family in northern Sweden. (16670064)
2006
28
Periodontal status in two siblings with severe congenital neutropenia: diagnosis and mutational analysis of the cases. (15898946)
2005
29
Cellular and molecular abnormalities in severe congenital neutropenia predisposing to leukemia. (12763135)
2003
30
The relationship between periodontal status and peripheral levels of neutrophils in two consanguineous siblings with severe congenital neutropenia: case reports. (12731605)
2003
31
Long-term follow-up of granulocyte colony-stimulating factor receptor mutations in patients with severe congenital neutropenia: implications for leukaemogenesis and therapy. (12588357)
2003
32
Mice expressing a neutrophil elastase mutation derived from patients with severe congenital neutropenia have normal granulopoiesis. (12384420)
2002
33
Defects of granulopoiesis in patients with severe congenital neutropenia. (12422946)
2002
34
The carboxyl terminus of the granulocyte colony-stimulating factor receptor, truncated in patients with severe congenital neutropenia/acute myeloid leukemia, is required for SH2-containing phosphatase-1 suppression of Stat activation. (11714811)
2001
35
Leukemic transformation in patients with severe congenital neutropenia. (11878775)
2001
36
Differential expression and regulation of GTPases (RhoA and Rac2) and GDIs (LyGDI and RhoGDI) in neutrophils from patients with severe congenital neutropenia. (10779444)
2000
37
Sustained receptor activation and hyperproliferation in response to granulocyte colony-stimulating factor (G-CSF) in mice with a severe congenital neutropenia/acute myeloid leukemia-derived mutation in the G-CSF receptor gene. (9989983)
1999
38
G-CSF receptor mutations in patients with severe congenital neutropenia do not abrogate Jak2 activation and stat1/stat3 translocation. (10372134)
1999
39
Deletion of a critical internalization domain in the G-CSFR in acute myelogenous leukemia preceded by severe congenital neutropenia. (9885205)
1999
40
Novel point mutation in the extracellular domain of the granulocyte colony-stimulating factor (G-CSF) receptor in a case of severe congenital neutropenia hyporesponsive to G-CSF treatment. (10449521)
1999
41
Clinical relevance of point mutations in the cytoplasmic domain of the granulocyte colony-stimulating factor receptor gene in patients with severe congenital neutropenia. (9116280)
1997
42
Mutations in the granulocyte colony-stimulating factor receptor gene in patients with severe congenital neutropenia. (9001427)
1997
43
Severe congenital neutropenia: a case study. (9429449)
1997
44
Severe congenital neutropenia terminating in acute myeloid leukemia: disease progression associated with mutations in the granulocyte-colony stimulating factor receptor gene. (8913314)
1996
45
The protein tyrosine kinase JAK2 is activated in neutrophils from patients with severe congenital neutropenia. (8541539)
1995
46
Cytokine profile during high-dose rhG-CSF therapy in severe congenital neutropenia. (7504401)
1994
47
Severe congenital neutropenia: abnormal growth and differentiation of myeloid progenitors to granulocyte colony-stimulating factor (G-CSF) but normal response to G-CSF plus stem cell factor. (7693032)
1993
48
Recombinant human stem cell factor, a c-kit ligand, stimulates granulopoiesis in severe congenital neutropenia. (7684187)
1993
49
Expression of receptors for granulocyte colony-stimulating factor on neutrophils from patients with severe congenital neutropenia and cyclic neutropenia. (1371412)
1992
50
In vitro functions of neutrophils induced by treatment with rhG-CSF in severe congenital neutropenia. (1704852)
1991

Genetic Variations for Severe Congenital Neutropenia

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Expression for genes affiliated with Severe Congenital Neutropenia

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1BioGPS, 15Gene Expression Omnibus DataSets
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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

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53Reactome, 29KEGG, 12EMD Millipore, 37NCBI BioSystems Database, 51QIAGEN
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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

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44Novoseek, 24HMDB, 11DrugBank, 49PharmGKB, 59Tocris Bioscience, 28IUPHAR, 2BitterDB
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Compounds related to Severe Congenital Neutropenia according to GeneCards/GeneDecks:

(show top 50)    (show all 59)
idCompoundScoreTop Affiliating Genes
1nadph44 2411.7PTPN6, RAC2
2valine4410.6ELANE, PTPN6
3pegfilgrastim44 1111.6CSF3R, CSF3, ELANE
4filgrastim44 1111.6ELANE, CSF3R, CSF3
5nitroblue tetrazolium4410.5FCGR1A, CSF3, CSF3R
6gemtuzumab ozogamicin44 1111.5CSF3, FCGR1A, FCGR3A
7alemtuzumab44 1111.5CSF3, FCGR3A, FCGR1A
8Palivizumab1110.5FCGR1A, FCGR3A
9anaphylatoxin4410.5C5AR1, ELANE, FPR1
10Intravenous Immunoglobulin1110.5FCGR3A, FCGR1A
11pentoxifylline44 1111.5FPR1, CAMP, ELANE
12cytochalasin b4410.5ELANE, C5AR1, FPR1
13tositumomab49 1111.4FCGR1A, FCGR3A
14Ibritumomab1110.4FCGR1A, FCGR3A
15gp 1304410.4CISH, CSF3R, CSF3, PTPN6
16cytochalasin d44 5911.4PTPN6, FCGR1A, CAMP, WAS
17dexamethasone44 49 28 1113.4FCGR1A, FPR1, CAMP, CISH
18rituximab44 49 1112.4CSF3, FCGR1A, FCGR3A
19bevacizumab49 1111.4FCGR3A, FCGR1A
20dbc-amp4410.4C5AR1, FPR1, CAMP
21n-formylmethionyl-leucylphenylalanine4410.3ELANE, CSF3, FPR1, C5AR1, RAC2
22alefacept44 1111.3FCGR3A, FCGR1A
23genistein44 28 59 2 11 2415.3FPR1, CAMP, PTPN6, FCGR1A, CSF3R
24fibrinogen4410.3ELANE, C5AR1, PTPN6, FCGR1A, FPR1
25phosphotyrosine4410.3PTPN6, FCGR3A, INPP5D, CISH, CSF3R
26phenylalanine4410.3C5AR1, PTPN6, FCGR3A, INPP5D, CSF3R
27arachidonic acid44 28 11 2413.2C5AR1, CAMP, RAC2, FPR1, FCGR1A
28wortmannin4410.2FPR1, INPP5D, CAMP, WAS, C5AR1
29endotoxin4410.2CAMP, ELANE, C5AR1, FPR1, CSF3, CSF3R
30pge24410.2FCGR1A, FPR1, CAMP, ELANE, C5AR1
31gtp44 2811.2ARHGDIB, FPR1, RAC2, WAS, C5AR1
32heparin44 28 11 2413.2C5AR1, FPR1, CSF3R, CAMP, ELANE
33thymidine44 2411.2CAMP, PTPN6, CSF3, INPP5D, CSF3R
34phosphoinositide4410.1C5AR1, CISH, INPP5D, FPR1, RAC2, PTPN6
35vegf4410.1CSF3, CSF3R, CAMP, PTPN6, C5AR1, FPR1
36asparagine4410.1FCGR3A, RAC2, C5AR1
37oxygen44 2411.1FCGR1A, ELANE, CSF3R, C5AR1, FPR1, RAC2
38retinoic acid44 2411.0CSF3, PTPN6, FPR1, CSF3R, CAMP, ELANE
39leukotriene b444 59 2412.0FPR1, C5AR1, ELANE
40oligonucleotide4410.0CSF3R, C5AR1, GFI1, CAMP, CISH, FPR1
41h2o24410.0ELANE, PTPN6, FCGR1A, FPR1, C5AR1
42superoxide44 2411.0ELANE, C5AR1, PTPN6, FCGR1A, RAC2, FPR1
43histamine44 28 2412.0C5AR1, INPP5D, CAMP, FPR1
44fmlp449.9ELANE, C5AR1, FCGR3A, FCGR1A, RAC2, FPR1
45phosphatidylinositol449.8RAC2, CISH, INPP5D, FPR1, FCGR3A, PTPN6
46lipid449.7PTPN6, RAC2, FCGR1A, INPP5D, C5AR1, CAMP
47phospholipid449.6C5AR1, INPP5D, PTPN6, CAMP
48serine449.6FCGR1A, CISH, WAS, CSF3R, CAMP, FPR1
49calcium44 49 11 2412.5CAMP, C5AR1, PTPN6, FCGR3A, FCGR1A, RAC2
50tyrosine449.1CISH, CSF3, CSF3R, CAMP, LEF1, ARHGDIB

GO Terms for genes affiliated with Severe Congenital Neutropenia

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16Gene Ontology
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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

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Sources for Severe Congenital Neutropenia

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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