MCID: HMP002
MIFTS: 54

Hemophagocytic Lymphohistiocytosis malady

Genetic diseases, Rare diseases, Immune diseases, Blood diseases, Neuronal diseases categories

Aliases & Classifications for Hemophagocytic Lymphohistiocytosis

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Sources:
30LifeMap Discovery®, 9Disease Ontology, 41NIH Rare Diseases, 20GeneTests, 21Genetics Home Reference, 11DISEASES, 43Novoseek, 47Orphanet, 22GTR, 60UMLS, 55SNOMED-CT, 33MeSH, 38NCIt, 27ICD9CM, 26ICD10 via Orphanet, 61UMLS via Orphanet, 25ICD10
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Hemophagocytic Lymphohistiocytosis, Aliases & Descriptions:

Name: Hemophagocytic Lymphohistiocytosis 30 9 41 11
Familial Hemophagocytic Lymphohistiocytosis 41 20 21 43 47 22
Familial Erythrophagocytic Lymphohistiocytosis 41 21
Familial Hemophagocytic Lymphocytosis 21 60
Hemophagocytic Syndrome 9 21
Familial Hlh 41 47
Fhl 41 21
Primary Hemophagocytic Hymphohistiocytosis 21
Familial Hemophagocytic Histiocytosis 21
Lymphohistiocytosis, Hemophagocytic 60
 
Familial Hemophagocytic Reticulosis 21
Lymphohistiocytosis Hemophagocytic 43
Familial Histiocytic Reticulosis 41
Haemophagocytic Syndrome 9
Hantavirus Infections 60
Hplh 21
Fhlh 21
Hps 9
Fel 21
Hlh 41


Classifications:



Characteristics (Orphanet epidemiological data):

47
familial hemophagocytic lymphohistiocytosis:
Inheritance: Autosomal recessive; Prevalence: 1-9/100000 (Sweden); Age of onset: Adolescent,Infancy


External Ids:

Disease Ontology9 DOID:0050120
ICD9CM27 288.4
Orphanet47 540
ICD10 via Orphanet26 D76.1
UMLS via Orphanet61 C0272199
ICD1025 D76.1

Summaries for Hemophagocytic Lymphohistiocytosis

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NIH Rare Diseases:41 Hemophagocytic lymphohistiocytosis (hlh) is a condition in which the body makes too many activated immune cells (macrophages and lymphocytes). people with hlh usually develop symptoms within the first months or years of life which may include fever, enlarged liver or spleen, cytopenia (lower-than-normal number of blood cells), and neurological abnormalities. hlh may be inherited in an autosomal recessive manner or it can have non-genetic causes in which case it is called acquired hlh. there are five subtypes of inherited hlh which are designated familial hlh, types 1-5. each subtype is caused by a change (mutation) in a different gene. the genetic cause of type 1 is currently unknown. types 2-5 are caused by mutations in the prf1 gene, the unc13d gene, the stx11 gene and the stxbp2 gene, respectively. treatment depends on a number of factors, including the severity of symptoms, the age of onset, and the underlying cause of the condition. last updated: 11/9/2014

MalaCards based summary: Hemophagocytic Lymphohistiocytosis, also known as familial hemophagocytic lymphohistiocytosis, is related to griscelli syndrome, type 2 and chediak-higashi syndrome. An important gene associated with Hemophagocytic Lymphohistiocytosis is PRF1 (perforin 1 (pore forming protein)), and among its related pathways are wtCFTR and deltaF508 traffic Late endosome and Lysosome norm and CF and Deregulation of Rab and Rab Effector Genes in Bladder Cancer. The compound chromium have been mentioned in the context of this disorder. Affiliated tissues include liver, spleen and t cells, and related mouse phenotypes are behavior/neurological and homeostasis/metabolism.

Disease Ontology:9 A lymphatic system disease that is characterized by an expansion of the monocyte-macrophage population and intense hemophagocytosis. it can occur de novo, but more often occurs in the setting of another disorder, usually an infection or a malignancy. a clinical picture of fever, hepatosplenomegaly, lymphadenopathy and peripheral pancytopenia. the morphologic hallmark of this syndrome is the phagocytosis of hematopoietic elements by morphologically normal macrophages.

Genetics Home Reference:21 Familial hemophagocytic lymphohistiocytosis is a disorder in which the immune system produces too many activated immune cells (lymphocytes) called T cells, natural killer cells, B cells, and macrophages (histiocytes). Excessive amounts of immune system proteins called cytokines are also produced. This overactivation of the immune system causes fever and damages the liver and spleen, resulting in enlargement of these organs.

Wikipedia:63 Hemophagocytic lymphohistiocytosis (HLH), also known as haemophagocytic lymphohistiocytosis (British... more...

Related Diseases for Hemophagocytic Lymphohistiocytosis

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Diseases in the Hemophagocytic Lymphohistiocytosis family:

Hemophagocytic Lymphohistiocytosis, Familial, 4 Hemophagocytic Lymphohistiocytosis, Familial, 1
Hemophagocytic Lymphohistiocytosis, Familial, 2 Hemophagocytic Lymphohistiocytosis, Familial, 3
Hemophagocytic Lymphohistiocytosis, Familial, 5

Diseases related to Hemophagocytic Lymphohistiocytosis via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50)    (show all 296)
idRelated DiseaseScoreTop Affiliating Genes
1griscelli syndrome, type 230.6RAB27A, UNC13D
2chediak-higashi syndrome30.5UNC13D, SH2D1A, STX11, RAB27A
3leukemia10.9
4hemophagocytic lymphohistiocytosis, familial, 110.7
5hematopoietic stem cell transplantation10.7
6macrophage activation syndrome10.7
7hemophagocytic lymphohistiocytosis, familial, 410.7
8hemophagocytic lymphohistiocytosis, familial, 310.6
9hemophagocytic lymphohistiocytosis, familial, 210.6
10visceral leishmaniasis10.6
11leishmaniasis10.6
12lymphoblastic leukemia10.6
13hemophagocytic reticulosis10.6
14hypoplastic left heart syndrome10.6
15hemophagocytic lymphohistiocytosis, familial, 510.5
16kawasaki disease10.5
17influenza10.5
18malignant histiocytosis10.5
19arthritis10.5
20hepatitis10.5
21pneumonia10.5
22tuberculosis10.5
23hemorrhagic fever10.5
24anhaptoglobinemia10.5
25hantavirus pulmonary syndrome10.5
26hodgkin lymphoma10.5
27anaplastic large cell lymphoma10.5
28chronic granulomatous disease10.5
29chronic lymphocytic leukemia10.5
30panniculitis10.5
31griscelli syndrome10.5
32hydrops fetalis10.5
33precursor b-cell acute lymphoblastic leukemia10.5
34acute liver failure10.4
35crohn's disease10.4
36dengue hemorrhagic fever10.4
37hemolytic anemia10.4
38myelofibrosis10.4
39peripheral t-cell lymphoma10.4
40autoimmune hemolytic anemia10.4
41hepatitis a10.4
42scrub typhus10.4
43dermatomyositis10.4
44ehrlichiosis10.4
45herpes simplex10.4
46histoplasmosis10.4
47myeloid leukemia10.4
48typhus10.4
49cytomegalovirus infection10.4
50acquired hemophagocytic lymphohistiocytosis associated with a malignant disease10.4

Graphical network of the top 20 diseases related to Hemophagocytic Lymphohistiocytosis:



Diseases related to hemophagocytic lymphohistiocytosis

Symptoms for Hemophagocytic Lymphohistiocytosis

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Drugs & Therapeutics for Hemophagocytic Lymphohistiocytosis

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Drug clinical trials:

Search ClinicalTrials for Hemophagocytic Lymphohistiocytosis

Search NIH Clinical Center for Hemophagocytic Lymphohistiocytosis

Cell-based therapeutics:


LifeMap Discovery
Data from LifeMap, the Embryonic Development and Stem Cells Database
Read about Hemophagocytic Lymphohistiocytosis cell therapies at LifeMap Discovery.
Stem-cell-based therapeutic approaches for Hemophagocytic Lymphohistiocytosis:
ALD-151, umbilical cord blood cells for hematologic and immunodefeciency diseases
Embryonic/Adult Cultured Cells Related to Hemophagocytic Lymphohistiocytosis:
Umbilical cord blood ALDH+ cells (ALD-151), PMID: 10430905

Genetic Tests for Hemophagocytic Lymphohistiocytosis

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Genetic tests related to Hemophagocytic Lymphohistiocytosis:

id Genetic test Affiliating Genes
1 Familial Hemophagocytic Lymphohistiocytosis20 22 UNC13D

Anatomical Context for Hemophagocytic Lymphohistiocytosis

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MalaCards organs/tissues related to Hemophagocytic Lymphohistiocytosis:

31
Liver, Spleen, T cells, B cells, Monocytes, Bone marrow, Bone, Kidney, Brain, Skin, Myeloid, Nk cells, Lung, Spinal cord, Colon, Pancreas, Tonsil, Neutrophil

Animal Models for Hemophagocytic Lymphohistiocytosis or affiliated genes

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MGI Mouse Phenotypes related to Hemophagocytic Lymphohistiocytosis:

35
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053868.5RAB27A, STX11, PRF1, GK, GDF15, SLC40A1
2MP:00053767.5RAB27A, STX11, PRF1, IRF5, SH2D1A, GK
3MP:00053877.2PRF1, IRF5, SH2D1A, TNFSF12, UNC13D, STX11
4MP:00053976.9GDF15, SLC40A1, RAB27A, SRGN, STXBP2, STX11

Publications for Hemophagocytic Lymphohistiocytosis

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Articles related to Hemophagocytic Lymphohistiocytosis:

(show top 50)    (show all 588)
idTitleAuthorsYear
1
Elevated serum adenosine deaminase levels in secondary hemophagocytic lymphohistiocytosis. (25764155)
2015
2
Epstein-barr virus-related hemophagocytic lymphohistiocytosis: hematologic emergency in the critical care setting. (25755898)
2015
3
Infantile hemophagocytic lymphohistiocytosis in a case of chediak-higashi syndrome caused by a mutation in the LYST/CHS1 gene presenting with delayed umbilical cord detachment and diarrhea. (25551669)
2015
4
Hodgkin's Lymphoma Revealed by Hemophagocytic Lymphohistiocytosis in a Child. (25328742)
2014
5
Hemophagocytic lymphohistiocytosis associated with cytomegalovirus infection in an immunocompetent infant: a diagnostic and therapeutic challenge! (25332603)
2014
6
Hemophagocytic Lymphohistiocytosis (HLH) Associated with T-Cell Lymphomas: Broadening our Differential for Fever of Unknown Origin. (25317396)
2014
7
Marrow assessment for hemophagocytic lymphohistiocytosis demonstrates poor correlation with disease probability. (24343738)
2014
8
Acute brucellosis with typical hemophagocytic lymphohistiocytosis accompanying elevated tumor markers. (25305773)
2014
9
Spectrum of imaging appearances in Australian children with central nervous system hemophagocytic lymphohistiocytosis. (24119957)
2014
10
Cognitive and psychosocial function post hematopoietic stem cell transplantation in children with hemophagocytic lymphohistiocytosis. (23987797)
2013
11
Hemophagocytic lymphohistiocytosis in a newborn infant born to a mother with SjAPgren syndrome antibodies. (23803677)
2013
12
Etoposide-containing conditioning regimen reduces the occurrence of hemophagocytic lymphohistiocytosis after SCT. (24037021)
2013
13
Undiagnosed Chronic Granulomatous Disease, Burkholderia cepacia complex Pneumonia, and Acquired Hemophagocytic Lymphohistiocytosis: A Deadly Association. (24058739)
2013
14
X-linked inhibitor of apoptosis (XIAP) deficiency: the spectrum of presenting manifestations beyond hemophagocytic lymphohistiocytosis. (23973892)
2013
15
Defects in neutrophil granule mobilization and bactericidal activity in familial hemophagocytic lymphohistiocytosis type 5 (FHL-5) syndrome caused by STXBP2/Munc18-2 mutations. (23687090)
2013
16
CNS involvement at the onset of primary hemophagocytic lymphohistiocytosis. (22422896)
2012
17
Recent advances in the diagnosis and treatment of hemophagocytic lymphohistiocytosis. (22682420)
2012
18
Enteric Fever presenting as secondary hemophagocytic lymphohistiocytosis. (22415495)
2012
19
Hemophagocytic lymphohistiocytosis can mimic the superior vena cava syndrome. (22395213)
2012
20
Familial hemophagocytic lymphohistiocytosis and X-linked lymphoproliferative disease. (22129058)
2011
21
Serum neopterin levels as a diagnostic marker of hemophagocytic lymphohistiocytosis syndrome. (21270283)
2011
22
Cytotoxic T-lymphocyte-associated antigen 4 gene polymorphisms in Japanese children with infection-associated hemophagocytic lymphohistiocytosis. (20224272)
2010
23
STX11 mutations and clinical phenotypes of familial hemophagocytic lymphohistiocytosis in North America. (20486178)
2010
24
Myelodysplastic syndrome (MDS) as a late stage of subclinical hemophagocytic lymphohistiocytosis (HLH): a putative role for Leptospira infection. A hypothesis. (20870590)
2010
25
Alemtuzumab as a bridge to allogeneic SCT in atypical hemophagocytic lymphohistiocytosis. (20404855)
2010
26
Munc18-2 deficiency causes familial hemophagocytic lymphohistiocytosis type 5 and impairs cytotoxic granule exocytosis in patient NK cells. (19884660)
2009
27
Hemophagocytic lymphohistiocytosis (HLH) and related disorders. (20008190)
2009
28
False positivity of FDG-PET during hemophagocytic lymphohistiocytosis in a child with Hodgkin lymphoma in remission. (19125095)
2009
29
Infection of T lymphocytes in non-Asian patients with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis. (19533652)
2009
30
Genetic loci contributing to hemophagocytic lymphohistiocytosis do not confer susceptibility to systemic-onset juvenile idiopathic arthritis. (18311812)
2008
31
The role of hemophagocytosis in bone marrow aspirates in the diagnosis of hemophagocytic lymphohistiocytosis. (18061932)
2008
32
Characterization of PRF1, STX11 and UNC13D genotype-phenotype correlations in familial hemophagocytic lymphohistiocytosis. (18710388)
2008
33
A Griscelli syndrome type 2 murine model of hemophagocytic lymphohistiocytosis (HLH). (18991284)
2008
34
Mutations of the hemophagocytic lymphohistiocytosis-associated gene UNC13D in a patient with systemic juvenile idiopathic arthritis. (18240215)
2008
35
Myelofibrosis in a child with EBV-associated hemophagocytic lymphohistiocytosis. (18454467)
2008
36
CNS involvement in hemophagocytic lymphohistiocytosis: CT and MR findings. (17277568)
2007
37
Two cases of ampulla (takotsubo-shaped) cardiomyopathy associated with hemophagocytic lymphohistiocytosis. (17215570)
2007
38
An unusual cause of ascites: hemophagocytic lymphohistiocytosis. (17536139)
2007
39
Severe autoimmune hemolytic anemia after unrelated umbilical cord blood transplant for familial hemophagocytic lymphohistiocytosis: significant improvement after treatment with rituximab. (17279011)
2007
40
Cerebrospinal fluid involvement in a case of visceral leishmaniasis associated with hemophagocytic lymphohistiocytosis. (21748112)
2007
41
Nationwide survey of hemophagocytic lymphohistiocytosis in Japan. (17675268)
2007
42
HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. (16937360)
2007
43
Mutation spectrum in children with primary hemophagocytic lymphohistiocytosis: molecular and functional analyses of PRF1, UNC13D, STX11, and RAB27A. (16278825)
2006
44
Disseminated hyperkeratotic and granulomatous nodules in a child with fatal Epstein-Barr-virus-associated hemophagocytic lymphohistiocytosis. (16445409)
2006
45
Evaluation of apoptosis in Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis. (16419109)
2006
46
A functional analysis of the putative polymorphisms A91V and N252S and 22 missense perforin mutations associated with familial hemophagocytic lymphohistiocytosis. (15755897)
2005
47
The role of infections in primary hemophagocytic lymphohistiocytosis: a case series and review of the literature. (11595993)
2001
48
Reduced Tyk2/SHP-1 interaction and lack of SHP-1 mutation in a kindred of familial hemophagocytic lymphohistiocytosis. (9519782)
1998
49
Familial hemophagocytic lymphohistiocytosis. Differential diagnosis with secondary hemophagocytic syndromes]. (9406478)
1997
50
Treatment of familial hemophagocytic lymphohistiocytosis with bone marrow transplantation from HLA genetically nonidentical donors. (9389690)
1997

Variations for Hemophagocytic Lymphohistiocytosis

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Clinvar genetic disease variations for Hemophagocytic Lymphohistiocytosis:

6 (show all 30)
id Gene Variation Type Significance SNP ID Assembly Location
1PRF1PRF1, 1-BP DEL, 50TdeletionPathogenic
2PRF1NM_001083116.1(PRF1): c.190C> T (p.Gln64Ter)single nucleotide variantPathogenicrs104894180GRCh37Chr 10, 72360469: 72360469
3PRF1NM_001083116.1(PRF1): c.673C> T (p.Arg225Trp)single nucleotide variantPathogenicrs28933973GRCh37Chr 10, 72358804: 72358804
4PRF1NM_001083116.1(PRF1): c.1286G> A (p.Gly429Glu)single nucleotide variantPathogenicrs104894181GRCh37Chr 10, 72358191: 72358191
5PRF1NM_001083116.1(PRF1): c.1034C> T (p.Pro345Leu)single nucleotide variantPathogenicrs28933374GRCh37Chr 10, 72358443: 72358443
6PRF1NM_001083116.1(PRF1): c.836G> A (p.Cys279Tyr)single nucleotide variantPathogenicrs104894182GRCh37Chr 10, 72358641: 72358641
7PRF1NM_001083116.1(PRF1): c.548T> G (p.Val183Gly)single nucleotide variantPathogenicrs104894183GRCh37Chr 10, 72358929: 72358929
8PRF1NM_001083116.1(PRF1): c.1304C> T (p.Thr435Met)single nucleotide variantPathogenicrs28933376GRCh37Chr 10, 72358173: 72358173
9PRF1PRF1, 2-BP DEL, 1090CTdeletionPathogenic
10PRF1PRF1, 1-BP DEL, 207AdeletionPathogenic
11PRF1NM_001083116.1(PRF1): c.1246C> T (p.Gln416Ter)single nucleotide variantPathogenicrs193302876GRCh37Chr 10, 72358231: 72358231
12UNC13DUNC13D, 12-BP DEL, NT1822deletionPathogenic
13UNC13DUNC13D, 1-BP DEL, 214CdeletionPathogenic
14UNC13DUNC13D, 1-BP INS, 1755TinsertionPathogenic
15UNC13DUNC13D, IVS15DS, G-A, +1single nucleotide variantPathogenic
16UNC13DNM_199242.2(UNC13D): c.766C> T (p.Arg256Ter)single nucleotide variantPathogenicrs121434352GRCh37Chr 17, 73836398: 73836398
17UNC13DUNC13D, IVS9DS, G-T, +1single nucleotide variantPathogenic
18UNC13DNM_199242.2(UNC13D): c.1208T> C (p.Leu403Pro)single nucleotide variantPathogenicrs121434353GRCh37Chr 17, 73832743: 73832743
19UNC13DNM_199242.2(UNC13D): c.2570T> G (p.Phe857Cys)single nucleotide variantPathogenicrs121434354GRCh37Chr 17, 73827234: 73827234
20STXBP2NM_006949.3(STXBP2): c.1621G> A (p.Gly541Ser)single nucleotide variantPathogenicrs61736587GRCh37Chr 19, 7712322: 7712322
21STX11NM_003764.3(STX11): c.369_376delAGTGGCGCinsTGG (p.Val124Glyfs)indelPathogenicrs483352901GRCh37Chr 6, 144508133: 144508140
22STX11NM_003764.3: c.-5-9734_*8586del19189deletionPathogenicGRCh38Chr 6, 144176889: 144196077
23STX11NM_003764.3(STX11): c.802C> T (p.Gln268Ter)single nucleotide variantPathogenicrs104893996GRCh37Chr 6, 144508566: 144508566
24STXBP2NM_006949.3(STXBP2): c.1430C> T (p.Pro477Leu)single nucleotide variantPathogenicrs121918540GRCh37Chr 19, 7711208: 7711208
25STXBP2STXBP2, 3-BP DEL, 693GATdeletionPathogenic
26STXBP2STXBP2, IVS14AS, G-C, -1single nucleotide variantPathogenic
27STXBP2NM_006949.3(STXBP2): c.626T> C (p.Leu209Pro)single nucleotide variantPathogenicrs121918541GRCh37Chr 19, 7706967: 7706967
28STXBP2STXBP2, 1-BP DEL, 260TdeletionPathogenic
29STXBP2STXBP2, 1-BP DEL, 706GdeletionPathogenic
30STX11NM_003764.3(STX11): c.173T> C (p.Leu58Pro)single nucleotide variantPathogenicrs431905512GRCh37Chr 6, 144507937: 144507937

Expression for genes affiliated with Hemophagocytic Lymphohistiocytosis

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Search GEO for disease gene expression data for Hemophagocytic Lymphohistiocytosis.

Pathways for genes affiliated with Hemophagocytic Lymphohistiocytosis

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Pathways related to Hemophagocytic Lymphohistiocytosis according to GeneCards Suite gene sharing:

idSuper pathways (with members indented)ScoreTop Affiliating Genes
19.9UNC13D, RAB27A
29.9RAB27A, UNC13D
39.8GDF15, SH2D1A
49.5IRF5, GDF15, SH2D1A
5
Show member pathways
Immune response CD16 signaling in NK cells58
9.4SH2D1A, PRF1, KIR2DS5

Compounds for genes affiliated with Hemophagocytic Lymphohistiocytosis

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Sources:
43Novoseek
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Compounds related to Hemophagocytic Lymphohistiocytosis according to GeneCards Suite gene sharing:

idCompoundScoreTop Affiliating Genes
1chromium439.4PRF1, GNLY

GO Terms for genes affiliated with Hemophagocytic Lymphohistiocytosis

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Cellular components related to Hemophagocytic Lymphohistiocytosis according to GeneCards Suite gene sharing:

idNameGO IDScoreTop Affiliating Genes
1exocytic vesicleGO:00703829.9RAB27A, UNC13D
2cytolytic granuleGO:00441949.7STXBP2, PRF1

Biological processes related to Hemophagocytic Lymphohistiocytosis according to GeneCards Suite gene sharing:

(show all 7)
idNameGO IDScoreTop Affiliating Genes
1cytotoxic T cell degranulationGO:004331610.0STX11, RAB27A
2regulation of mast cell degranulationGO:004330410.0UNC13D, STXBP2
3neutrophil degranulationGO:00433129.9STX11, STXBP2
4natural killer cell degranulationGO:00433209.8UNC13D, STX11, RAB27A
5defense response to virusGO:00516079.7PRF1, IRF5, UNC13D
6positive regulation of exocytosisGO:00459219.6RAB27A, UNC13D
7cellular defense responseGO:00069689.2PRF1, SH2D1A, GNLY

Molecular functions related to Hemophagocytic Lymphohistiocytosis according to GeneCards Suite gene sharing:

idNameGO IDScoreTop Affiliating Genes
1protein bindingGO:00055156.6SLC40A1, UNC13D, TNFSF12, SH2D1A, IRF5, PRF1

Products for genes affiliated with Hemophagocytic Lymphohistiocytosis

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Sources for Hemophagocytic Lymphohistiocytosis

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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