MCID: HMP022
MIFTS: 54

Hemophagocytic Lymphohistiocytosis, Familial, 1

Categories: Rare diseases, Blood diseases, Neuronal diseases, Immune diseases, Genetic diseases

Aliases & Classifications for Hemophagocytic Lymphohistiocytosis, Familial, 1

MalaCards integrated aliases for Hemophagocytic Lymphohistiocytosis, Familial, 1:

Name: Hemophagocytic Lymphohistiocytosis, Familial, 1 53 13
Familial Hemophagocytic Lymphohistiocytosis 1 12 28 14
Hemophagocytic Lymphohistiocytosis, Familial 53 23
Hplh1 53 12
Fhl1 53 12
Hlh1 53 12
Hemophagocytic Lymphohistiocytosis, Familial; Fhl; Fhlh; Hplh 53
Erythrophagocytic Lymphohistiocytosis, Familial; Fel 53
Erythrophagocytic Lymphohistiocytosis, Familial 53
Familial Erythrophagocytic Lymphohistiocytosis 23
Familial Hemophagocytic Lymphocytosis 69
Hemophagocytic Reticulosis, Familial 53
Reticulosis, Familial Histiocytic 53
Fhlh 23
Fhl 53
Fel 53

Characteristics:

OMIM:

53
Inheritance:
autosomal recessive


HPO:

31
hemophagocytic lymphohistiocytosis, familial, 1:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Hemophagocytic Lymphohistiocytosis, Familial, 1

OMIM : 53 Zur Stadt et al. (2005) summarized the clinical features of hemophagocytic lymphohistiocytosis (HLH), a rare autosomal recessive disorder characterized by massive infiltration of several organs by activated lymphocytes and macrophages. The clinical features of the disease include fever, hepatosplenomegaly, cytopenia, and less frequently central nervous system involvement. In FHL, the familial form of the disease, first episodes occur mostly during infancy, with a rapidly fatal outcome if untreated. Diagnostic criteria also include low fibrinogen and high triglyceride and ferritin levels. Chemoimmunotherapy based on corticosteroids, epipodophyllotoxins, and cyclosporin succeeds in controlling the disease in the majority of patients, although remission is rarely obtained (Henter et al., 2002). Most patients suffer an early death unless they are treated by hematopoietic stem cell transplantation (Durken et al., 1999). (267700)

MalaCards based summary : Hemophagocytic Lymphohistiocytosis, Familial, 1, also known as familial hemophagocytic lymphohistiocytosis 1, is related to hemophagocytic lymphohistiocytosis, familial, 2 and hemophagocytic lymphohistiocytosis, familial, 4, and has symptoms including ataxia, seizures and hemiplegia. An important gene associated with Hemophagocytic Lymphohistiocytosis, Familial, 1 is PRF1 (Perforin 1), and among its related pathways/superpathways are Regulation of actin dynamics for phagocytic cup formation and Signaling by PTK6. The drugs Anti-Infective Agents and Antibodies have been mentioned in the context of this disorder. Affiliated tissues include t cells, liver and bone, and related phenotypes are homeostasis/metabolism and cardiovascular system

Disease Ontology : 12 A hemophagocytic lymphohistiocytosis that has material basis in an autosomal recessive mutation of HPLH1 on chromosome 9q21.3-q22.

GeneReviews: NBK1444

Related Diseases for Hemophagocytic Lymphohistiocytosis, Familial, 1

Diseases in the Hemophagocytic Lymphohistiocytosis family:

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

Diseases related to Hemophagocytic Lymphohistiocytosis, Familial, 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 47)
# Related Disease Score Top Affiliating Genes
1 hemophagocytic lymphohistiocytosis, familial, 2 31.7 DOCK1 ELMO2 IFT122 PRF1 WDR35
2 hemophagocytic lymphohistiocytosis, familial, 4 12.3
3 hemophagocytic lymphohistiocytosis, familial, 3 12.3
4 hemophagocytic lymphohistiocytosis, familial, 5 12.3
5 reducing body myopathy 11.9
6 scapuloperoneal myopathy, x-linked dominant 11.7
7 myopathy, x-linked, with postural muscle atrophy 11.6
8 myopathy 11.5
9 emery-dreifuss muscular dystrophy 11.5
10 muscular dystrophy 11.5
11 scapuloperoneal myopathy 11.5
12 muscle hypertrophy 11.4
13 rigid spine muscular dystrophy 1 11.3
14 hypertrophic cardiomyopathy 11.3
15 myofibrillar myopathy 11.3
16 pulmonary artery hypoplasia 11.3
17 reducing body myopathy, x-linked 1a, severe, with infantile or early childhood onset 11.2
18 reducing body myopathy, x-linked 1b, with late childhood or adult onset 11.2
19 hemophagocytic lymphohistiocytosis 11.1
20 uruguay faciocardiomusculoskeletal syndrome 11.0
21 foot drop 10.9
22 emery-dreifuss muscular dystrophy, x-linked 10.8
23 lung cancer 10.5
24 gas gangrene 10.2 MYOD1 PRF1
25 central nervous system mesenchymal non-meningothelial tumor 10.1 MYF6 MYOD1
26 inflammatory leiomyosarcoma 10.1 MYF6 MYOD1
27 conventional leiomyosarcoma 10.1 MYF6 MYOD1
28 extraosseous ewing's sarcoma 10.0 MYF6 MYOD1
29 chromophobe renal cell carcinoma 9.9
30 polycystic kidney disease 9.9
31 hemophagocytic reticulosis 9.9
32 gastric cancer 9.9
33 squamous cell carcinoma 9.9
34 skeletal muscle cancer 9.9 MYF6 MYOD1
35 cranioectodermal dysplasia 1 9.8 IFT122 WDR35
36 short-rib thoracic dysplasia 3 with or without polydactyly 9.8 IFT122 WDR35
37 clubfoot, congenital, with or without deficiency of long bones and/or mirror-image polydactyly 9.8
38 papillomatosis, confluent and reticulated 9.8
39 muscular dystrophy, duchenne type 9.8
40 aging 9.8
41 tongue squamous cell carcinoma 9.8
42 atrial fibrillation 9.8
43 hypoparathyroidism 9.8
44 clubfoot 9.8
45 prostatitis 9.8
46 talipes equinovarus 9.8
47 alveolar soft part sarcoma 9.7 MYF6 MYOD1

Graphical network of the top 20 diseases related to Hemophagocytic Lymphohistiocytosis, Familial, 1:



Diseases related to Hemophagocytic Lymphohistiocytosis, Familial, 1

Symptoms & Phenotypes for Hemophagocytic Lymphohistiocytosis, Familial, 1

Symptoms via clinical synopsis from OMIM:

53
Neurologic Central Nervous System:
ataxia
seizures
hemiplegia
encephalitis
tetraplegia
more
Growth Other:
failure to thrive

Abdomen Liver:
hepatomegaly

Hematology:
anemia
thrombocytopenia
leukopenia

Immunology:
lymphadenopathy
overproduction by t lymphocytes and macrophages of cytokines, particularly interferon gamma and tumor necrosis factor alpha
activated hla dr+ t cells in peripheral blood
reduced natural killer cell cytotoxicity
reduced t cell cytotoxicity
more
Head And Neck Head:
bulging fontanelle

Abdomen Spleen:
splenomegaly

Laboratory Abnormalities:
hypertriglyceridemia
hyponatremia
prolonged prothrombin time
hypoalbuminemia
hypoproteinemia
more
Skin Nails Hair Skin:
jaundice
purpuric rashes

Muscle Soft Tissue:
generalized edema


Clinical features from OMIM:

267700

Human phenotypes related to Hemophagocytic Lymphohistiocytosis, Familial, 1:

31 (show all 36)
# Description HPO Frequency HPO Source Accession
1 ataxia 31 HP:0001251
2 seizures 31 HP:0001250
3 hemiplegia 31 HP:0002301
4 failure to thrive 31 HP:0001508
5 encephalitis 31 HP:0002383
6 tetraplegia 31 HP:0002445
7 global developmental delay 31 HP:0001263
8 splenomegaly 31 HP:0001744
9 hepatomegaly 31 HP:0002240
10 increased intracranial pressure 31 HP:0002516
11 hypertonia 31 HP:0001276
12 hypertriglyceridemia 31 HP:0002155
13 anemia 31 HP:0001903
14 irritability 31 HP:0000737
15 thrombocytopenia 31 HP:0001873
16 jaundice 31 HP:0000952
17 coma 31 HP:0001259
18 hyponatremia 31 HP:0002902
19 meningitis 31 HP:0001287
20 lymphadenopathy 31 HP:0002716
21 increased serum ferritin 31 HP:0003281
22 leukopenia 31 HP:0001882
23 generalized hypotonia 31 HP:0001290
24 prolonged partial thromboplastin time 31 HP:0003645
25 prolonged prothrombin time 31 HP:0008151
26 increased csf protein 31 HP:0002922
27 hypoalbuminemia 31 HP:0003073
28 hypoproteinemia 31 HP:0003075
29 increased total bilirubin 31 HP:0003573
30 csf pleocytosis 31 HP:0012229
31 generalized edema 31 HP:0007430
32 hemophagocytosis 31 HP:0012156
33 hypofibrinogenemia 31 HP:0011900
34 decreased circulating high-density lipoprotein levels 31 HP:0003233
35 increased circulating low-density lipoprotein levels 31 HP:0003141
36 increased circulating very-low-density lipoprotein levels 31 HP:0003362

UMLS symptoms related to Hemophagocytic Lymphohistiocytosis, Familial, 1:


bulging fontanelle, seizures, icterus, hemiplegia, ataxia

MGI Mouse Phenotypes related to Hemophagocytic Lymphohistiocytosis, Familial, 1:

43
# Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 9.76 FHL1 IFT122 MYF6 MYOD1 PRF1 WDR35
2 cardiovascular system MP:0005385 9.73 DOCK1 FHL1 IFT122 MYOD1 PRF1 WDR35
3 muscle MP:0005369 9.35 DOCK1 FHL1 MYF6 MYOD1 WDR35
4 respiratory system MP:0005388 9.02 DOCK1 MYF6 MYOD1 STXBP2 WDR35

Drugs & Therapeutics for Hemophagocytic Lymphohistiocytosis, Familial, 1

Drugs for Hemophagocytic Lymphohistiocytosis, Familial, 1 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show top 50) (show all 65)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Anti-Infective Agents Phase 3,Phase 2
2 Antibodies Phase 2, Phase 3
3 Antibodies, Monoclonal Phase 2, Phase 3
4 Immunoglobulins Phase 2, Phase 3
5 Interferon-gamma Phase 2, Phase 3
6 interferons Phase 2, Phase 3
7 Antiviral Agents Phase 3,Phase 2
8
Cyclophosphamide Approved, Investigational Phase 2,Phase 1 50-18-0, 6055-19-2 2907
9
Busulfan Approved, Investigational Phase 1, Phase 2,Early Phase 1 55-98-1 2478
10
alemtuzumab Approved, Investigational Phase 2,Phase 1,Early Phase 1 216503-57-0
11
Cytarabine Approved, Investigational Phase 2 147-94-4 6253
12
Everolimus Approved Phase 1, Phase 2 159351-69-6 6442177
13
Fludarabine Approved Phase 1, Phase 2, Early Phase 1 21679-14-1, 75607-67-9 30751
14
Melphalan Approved Phase 1, Phase 2,Early Phase 1 148-82-3 460612 4053
15
Methylprednisolone Approved, Vet_approved Phase 1, Phase 2 83-43-2 6741
16
Prednisolone Approved, Vet_approved Phase 1, Phase 2 50-24-8 5755
17
Sirolimus Approved, Investigational Phase 1, Phase 2 53123-88-9 46835353 6436030 5284616
18
Tacrolimus Approved, Investigational Phase 1, Phase 2 104987-11-3 445643 439492
19 Thiotepa Approved, Investigational Phase 1, Phase 2 52-24-4 5453
20 Alkylating Agents Phase 2,Phase 1
21 Antimetabolites Phase 2,Phase 1
22 Antimetabolites, Antineoplastic Phase 2,Phase 1
23 Antirheumatic Agents Phase 2,Phase 1
24 Immunosuppressive Agents Phase 2,Phase 1
25 Calcineurin Inhibitors Phase 1, Phase 2
26 Antiemetics Phase 1, Phase 2
27 Anti-Inflammatory Agents Phase 1, Phase 2
28 Antineoplastic Agents, Hormonal Phase 1, Phase 2
29 Autonomic Agents Phase 1, Phase 2
30 Gastrointestinal Agents Phase 1, Phase 2
31 glucocorticoids Phase 1, Phase 2
32 Hormone Antagonists Phase 1, Phase 2
33 Hormones Phase 1, Phase 2
34 Hormones, Hormone Substitutes, and Hormone Antagonists Phase 1, Phase 2
35 Liver Extracts Phase 1, Phase 2
36 Methylprednisolone acetate Phase 1, Phase 2
37 Methylprednisolone Hemisuccinate Phase 1, Phase 2
38 Neuroprotective Agents Phase 1, Phase 2
39 Peripheral Nervous System Agents Phase 1, Phase 2
40 Pharmaceutical Solutions Phase 1, Phase 2
41 Prednisolone acetate Phase 1, Phase 2
42 Prednisolone hemisuccinate Phase 1, Phase 2
43 Prednisolone phosphate Phase 1, Phase 2
44 Protective Agents Phase 1, Phase 2
45
Etoposide Approved 33419-42-0 36462
46
Lenograstim Approved, Investigational 135968-09-1
47
Methotrexate Approved 1959-05-2, 59-05-2 126941
48
Miconazole Approved, Investigational, Vet_approved 22916-47-8 4189
49
Prednisone Approved, Vet_approved 53-03-2 5865
50
Folic Acid Approved, Nutraceutical, Vet_approved 59-30-3 6037

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 A Study to Investigate the Safety and Efficacy of an Anti-IFNγ mAb in Children Affected by Primary Haemophagocytic Lymphohistiocytosis Recruiting NCT01818492 Phase 2, Phase 3
2 Study to Assess the Efficacy and Safety of Emapalumab in Primary Haemophagocytic Lymphohistiocytosis Not yet recruiting NCT03312751 Phase 3 Emapalumab
3 T Cell Depletion for Recipients of HLA Haploidentical Related Donor Stem Cell Grafts Recruiting NCT00368355 Phase 2 Ara-C;Cyclophosphamide
4 CD34+ (Malignant) Stem Cell Selection for Patients Receiving Allogenic Stem Cell Transplant Recruiting NCT02061800 Phase 1, Phase 2 Thiotepa;Cyclophosphamide;Alemtuzumab;Tacrolimus;Melphalan;Busulfan;Fludarabine;Methylprednisolone
5 Administration of Donor T Cells With the Caspase-9 Suicide Gene Active, not recruiting NCT01494103 Phase 1 AP1903
6 CASPALLO: Allodepleted T Cells Transduced With Inducible Caspase 9 Suicide Gene Active, not recruiting NCT00710892 Phase 1
7 Pilot Study of Unrelated Donor Hematopoietic Stem Cell Transplantation in Patients With Life Threatening Hemophagocytic Disorders Unknown status NCT00006056 anti-thymocyte globulin;busulfan;cyclophosphamide;cyclosporine;etoposide;filgrastim;methotrexate
8 Investigation of the Role of FHL-1 and Myostatin in Intensive Care Unit Acquired Paresis (ICUAP) Completed NCT01321320
9 CD34+ (Non-Malignant) Stem Cell Selection for Patients Receiving Allogeneic Stem Cell Transplantation Recruiting NCT01966367 Early Phase 1
10 Allogeneic Bone Marrow Transplantation in Patients With Primary Immunodeficiencies Terminated NCT00006054 anti-thymocyte globulin;busulfan;cyclophosphamide;cyclosporine;etoposide;methotrexate;methylprednisolone;prednisone

Search NIH Clinical Center for Hemophagocytic Lymphohistiocytosis, Familial, 1

Genetic Tests for Hemophagocytic Lymphohistiocytosis, Familial, 1

Genetic tests related to Hemophagocytic Lymphohistiocytosis, Familial, 1:

# Genetic test Affiliating Genes
1 Familial Hemophagocytic Lymphohistiocytosis 1 28

Anatomical Context for Hemophagocytic Lymphohistiocytosis, Familial, 1

MalaCards organs/tissues related to Hemophagocytic Lymphohistiocytosis, Familial, 1:

38
T Cells, Liver, Bone, Bone Marrow, Lymph Node, Spleen

Publications for Hemophagocytic Lymphohistiocytosis, Familial, 1

Articles related to Hemophagocytic Lymphohistiocytosis, Familial, 1:

# Title Authors Year
1
Hemophagocytic Lymphohistiocytosis, Familial ( 20301617 )
1993

Variations for Hemophagocytic Lymphohistiocytosis, Familial, 1

ClinVar genetic disease variations for Hemophagocytic Lymphohistiocytosis, Familial, 1:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 PRF1 NM_001083116.2(PRF1): c.673C> T (p.Arg225Trp) single nucleotide variant Pathogenic rs28933973 GRCh37 Chromosome 10, 72358804: 72358804
2 UNC13D NM_199242.2(UNC13D): c.1389+1G> A single nucleotide variant Pathogenic/Likely pathogenic rs777759523 GRCh37 Chromosome 17, 73832419: 73832419
3 STXBP2 NM_006949.3(STXBP2): c.1247-1G> C single nucleotide variant Pathogenic rs140148806 GRCh37 Chromosome 19, 7710082: 7710082

Expression for Hemophagocytic Lymphohistiocytosis, Familial, 1

Search GEO for disease gene expression data for Hemophagocytic Lymphohistiocytosis, Familial, 1.

Pathways for Hemophagocytic Lymphohistiocytosis, Familial, 1

GO Terms for Hemophagocytic Lymphohistiocytosis, Familial, 1

Cellular components related to Hemophagocytic Lymphohistiocytosis, Familial, 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytosol GO:0005829 9.86 DOCK1 ELMO1 ELMO2 FHL1 IFT122 MYOD1
2 ciliary tip GO:0097542 9.32 IFT122 WDR35
3 guanyl-nucleotide exchange factor complex GO:0032045 9.16 DOCK1 ELMO1
4 intraciliary transport particle A GO:0030991 8.96 IFT122 WDR35
5 cytolytic granule GO:0044194 8.62 PRF1 STXBP2

Biological processes related to Hemophagocytic Lymphohistiocytosis, Familial, 1 according to GeneCards Suite gene sharing:

(show all 16)
# Name GO ID Score Top Affiliating Genes
1 apoptotic process GO:0006915 9.84 DOCK1 ELMO1 ELMO2 PRF1
2 cell migration GO:0016477 9.69 DOCK1 ELMO1 ELMO2
3 Fc-gamma receptor signaling pathway involved in phagocytosis GO:0038096 9.58 DOCK1 ELMO1 ELMO2
4 skeletal muscle tissue development GO:0007519 9.56 MYF6 MYOD1
5 skeletal muscle cell differentiation GO:0035914 9.55 MYF6 MYOD1
6 intraciliary transport involved in cilium assembly GO:0035735 9.52 IFT122 WDR35
7 muscle organ development GO:0007517 9.5 FHL1 MYF6 MYOD1
8 positive regulation of muscle cell differentiation GO:0051149 9.49 MYF6 MYOD1
9 positive regulation of myoblast differentiation GO:0045663 9.48 MYF6 MYOD1
10 protein localization to cilium GO:0061512 9.46 IFT122 WDR35
11 positive regulation of myoblast fusion GO:1901741 9.43 MYF6 MYOD1
12 intraciliary retrograde transport GO:0035721 9.37 IFT122 WDR35
13 vascular endothelial growth factor receptor signaling pathway GO:0048010 9.33 DOCK1 ELMO1 ELMO2
14 positive regulation of skeletal muscle fiber development GO:0048743 9.26 MYF6 MYOD1
15 muscle cell fate commitment GO:0042693 8.96 MYF6 MYOD1
16 phagocytosis GO:0006909 8.8 DOCK1 ELMO1 ELMO2

Molecular functions related to Hemophagocytic Lymphohistiocytosis, Familial, 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding GO:0003705 9.16 MYF6 MYOD1
2 E-box binding GO:0070888 8.96 MYF6 MYOD1
3 SH3 domain binding GO:0017124 8.8 DOCK1 ELMO1 ELMO2

Sources for Hemophagocytic Lymphohistiocytosis, Familial, 1

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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