MCID: HMP022
MIFTS: 50

Hemophagocytic Lymphohistiocytosis, Familial, 1

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

Aliases & Classifications for Hemophagocytic Lymphohistiocytosis, Familial, 1

MalaCards integrated aliases for Hemophagocytic Lymphohistiocytosis, Familial, 1:

Name: Hemophagocytic Lymphohistiocytosis, Familial, 1 57 13
Familial Hemophagocytic Lymphohistiocytosis 1 12 29 15
Hemophagocytic Lymphohistiocytosis, Familial 57 24
Hplh1 57 12
Fhl1 57 12
Hlh1 57 12
Hemophagocytic Lymphohistiocytosis, Familial; Fhl; Fhlh; Hplh 57
Erythrophagocytic Lymphohistiocytosis, Familial; Fel 57
Erythrophagocytic Lymphohistiocytosis, Familial 57
Familial Erythrophagocytic Lymphohistiocytosis 24
Familial Hemophagocytic Lymphocytosis 73
Hemophagocytic Reticulosis, Familial 57
Reticulosis, Familial Histiocytic 57
Fhlh 24
Fhl 57
Fel 57

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive


HPO:

32
hemophagocytic lymphohistiocytosis, familial, 1:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Hemophagocytic Lymphohistiocytosis, Familial, 1

OMIM : 57 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 myopathy, and has symptoms including ataxia, hemiplegia and icterus. An important gene associated with Hemophagocytic Lymphohistiocytosis, Familial, 1 is FHL1 (Four And A Half LIM Domains 1), and among its related pathways/superpathways are C-MYB transcription factor network and Myogenesis. The drugs Anti-Infective Agents and Antibodies have been mentioned in the context of this disorder. Affiliated tissues include t cells, bone marrow and bone, and related phenotypes are irritability and jaundice

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 32.1 ELMO2 IFT122 WDR35
2 myopathy 30.5 FHL1 MYF6 MYOD1
3 hemophagocytic lymphohistiocytosis, familial, 4 12.4
4 hemophagocytic lymphohistiocytosis, familial, 3 12.4
5 hemophagocytic lymphohistiocytosis, familial, 5 12.3
6 reducing body myopathy 11.9
7 scapuloperoneal myopathy, x-linked dominant 11.7
8 myopathy, x-linked, with postural muscle atrophy 11.6
9 emery-dreifuss muscular dystrophy 11.5
10 muscular dystrophy 11.5
11 scapuloperoneal myopathy 11.5
12 hypertrophic cardiomyopathy 11.4
13 muscle hypertrophy 11.4
14 rigid spine muscular dystrophy 1 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 squamous cell carcinoma 10.0
25 central nervous system mesenchymal non-meningothelial tumor 9.9 MYF6 MYOD1
26 chromophobe renal cell carcinoma 9.9
27 polycystic kidney disease 9.9
28 inflammatory leiomyosarcoma 9.9 MYF6 MYOD1
29 conventional leiomyosarcoma 9.9 MYF6 MYOD1
30 gastric cancer 9.9
31 extraosseous ewing's sarcoma 9.8 MYF6 MYOD1
32 skeletal muscle cancer 9.8 MYF6 MYOD1
33 clubfoot, congenital, with or without deficiency of long bones and/or mirror-image polydactyly 9.7
34 muscular dystrophy, duchenne type 9.7
35 aging 9.7
36 tongue squamous cell carcinoma 9.7
37 atrial fibrillation 9.7
38 hypoparathyroidism 9.7
39 distal muscular dystrophy 9.7
40 clubfoot 9.7
41 esophagitis 9.7
42 prostatitis 9.7
43 talipes equinovarus 9.7
44 alveolar soft part sarcoma 9.7 MYF6 MYOD1
45 cranioectodermal dysplasia 1 9.6 IFT122 WDR35
46 short-rib thoracic dysplasia 3 with or without polydactyly 9.4 IFT122 WDR35
47 asphyxiating thoracic dystrophy 9.2 IFT122 WDR35

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:

57
Neurologic Central Nervous System:
seizures
ataxia
encephalitis
tetraplegia
increased intracranial pressure
more
AbdomenSpleen:
splenomegaly

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

Muscle Soft Tissue:
generalized edema

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


Clinical features from OMIM:

267700

Human phenotypes related to Hemophagocytic Lymphohistiocytosis, Familial, 1:

32 (show all 37)
# Description HPO Frequency HPO Source Accession
1 irritability 32 HP:0000737
2 jaundice 32 HP:0000952
3 seizures 32 HP:0001250
4 ataxia 32 HP:0001251
5 muscular hypotonia 32 HP:0001252
6 coma 32 HP:0001259
7 global developmental delay 32 HP:0001263
8 hypertonia 32 HP:0001276
9 meningitis 32 HP:0001287
10 generalized hypotonia 32 HP:0001290
11 failure to thrive 32 HP:0001508
12 splenomegaly 32 HP:0001744
13 thrombocytopenia 32 HP:0001873
14 leukopenia 32 HP:0001882
15 anemia 32 HP:0001903
16 hypertriglyceridemia 32 HP:0002155
17 hepatomegaly 32 HP:0002240
18 hemiplegia 32 HP:0002301
19 encephalitis 32 HP:0002383
20 tetraplegia 32 HP:0002445
21 increased intracranial pressure 32 HP:0002516
22 lymphadenopathy 32 HP:0002716
23 hyponatremia 32 HP:0002902
24 increased csf protein 32 HP:0002922
25 hypoalbuminemia 32 HP:0003073
26 hypoproteinemia 32 HP:0003075
27 increased ldl cholesterol concentration 32 HP:0003141
28 decreased hdl cholesterol concentration 32 HP:0003233
29 increased serum ferritin 32 HP:0003281
30 Increased circulating very-low-density lipoprotein levels 32 HP:0003362
31 increased total bilirubin 32 HP:0003573
32 prolonged partial thromboplastin time 32 HP:0003645
33 generalized edema 32 HP:0007430
34 prolonged prothrombin time 32 HP:0008151
35 hypofibrinogenemia 32 HP:0011900
36 hemophagocytosis 32 HP:0012156
37 csf pleocytosis 32 HP:0012229

UMLS symptoms related to Hemophagocytic Lymphohistiocytosis, Familial, 1:


ataxia, hemiplegia, icterus, seizures, bulging fontanelle

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

46
# Description MGI Source Accession Score Top Affiliating Genes
1 muscle MP:0005369 8.92 FHL1 MYF6 MYOD1 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 66)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Anti-Infective Agents Phase 3,Phase 2,Not Applicable
2 Antibodies Phase 2, Phase 3,Phase 3
3 Antibodies, Monoclonal Phase 2, Phase 3,Phase 3
4 Immunoglobulins Phase 2, Phase 3,Phase 3
5 Interferon-gamma Phase 2, Phase 3,Phase 3
6 interferons Phase 2, Phase 3,Phase 3
7 Antiviral Agents Phase 3,Phase 2
8
Cyclophosphamide Approved, Investigational Phase 2,Phase 1,Not Applicable 50-18-0, 6055-19-2 2907
9
Busulfan Approved, Investigational Phase 1, Phase 2,Not Applicable,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,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 4053 460612
15
Methylprednisolone Approved, Vet_approved Phase 1, Phase 2,Not Applicable 83-43-2 6741
16
Prednisolone Approved, Vet_approved Phase 1, Phase 2,Not Applicable 50-24-8 5755
17
Sirolimus Approved, Investigational Phase 1, Phase 2 53123-88-9 5284616 6436030 46835353
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,Not Applicable
21 Antimetabolites Phase 2,Phase 1,Not Applicable
22 Antimetabolites, Antineoplastic Phase 2,Phase 1,Not Applicable
23 Antineoplastic Agents, Alkylating Phase 2,Phase 1,Not Applicable
24 Antirheumatic Agents Phase 2,Phase 1,Not Applicable
25 Immunosuppressive Agents Phase 2,Phase 1,Not Applicable
26 Calcineurin Inhibitors Phase 1, Phase 2,Not Applicable
27 Antiemetics Phase 1, Phase 2,Not Applicable
28 Anti-Inflammatory Agents Phase 1, Phase 2,Not Applicable
29 Antineoplastic Agents, Hormonal Phase 1, Phase 2,Not Applicable
30 Autonomic Agents Phase 1, Phase 2,Not Applicable
31 Gastrointestinal Agents Phase 1, Phase 2,Not Applicable
32 glucocorticoids Phase 1, Phase 2,Not Applicable
33 Hormone Antagonists Phase 1, Phase 2,Not Applicable
34 Hormones Phase 1, Phase 2,Not Applicable
35 Hormones, Hormone Substitutes, and Hormone Antagonists Phase 1, Phase 2,Not Applicable
36 Liver Extracts Phase 1, Phase 2
37 Methylprednisolone acetate Phase 1, Phase 2,Not Applicable
38 Methylprednisolone Hemisuccinate Phase 1, Phase 2,Not Applicable
39 Neuroprotective Agents Phase 1, Phase 2,Not Applicable
40 Peripheral Nervous System Agents Phase 1, Phase 2,Not Applicable
41 Pharmaceutical Solutions Phase 1, Phase 2
42 Prednisolone acetate Phase 1, Phase 2,Not Applicable
43 Prednisolone hemisuccinate Phase 1, Phase 2,Not Applicable
44 Prednisolone phosphate Phase 1, Phase 2,Not Applicable
45 Protective Agents Phase 1, Phase 2,Not Applicable
46
Etoposide Approved Not Applicable 33419-42-0 36462
47
Lenograstim Approved, Investigational Not Applicable 135968-09-1
48
Methotrexate Approved Not Applicable 1959-05-2, 59-05-2 126941
49
Miconazole Approved, Investigational, Vet_approved Not Applicable 22916-47-8 4189
50
Prednisone Approved, Vet_approved Not Applicable 53-03-2 5865

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 Not Applicable 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 Not Applicable
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 Not Applicable 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 29

Anatomical Context for Hemophagocytic Lymphohistiocytosis, Familial, 1

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

41
T Cells, Bone Marrow, Bone, Liver, 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

Expression for Hemophagocytic Lymphohistiocytosis, Familial, 1

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

Pathways for Hemophagocytic Lymphohistiocytosis, Familial, 1

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

# Super pathways Score Top Affiliating Genes
1 11.05 MYF6 MYOD1
2
Show member pathways
10.72 MYF6 MYOD1
3 10.24 IFT122 WDR35

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 ciliary basal body GO:0036064 9.16 IFT122 WDR35
2 ciliary tip GO:0097542 8.96 IFT122 WDR35
3 intraciliary transport particle A GO:0030991 8.62 IFT122 WDR35

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

(show all 13)
# Name GO ID Score Top Affiliating Genes
1 multicellular organism development GO:0007275 9.81 FHL1 IFT122 MYF6 MYOD1
2 cellular response to tumor necrosis factor GO:0071356 9.52 MYOD1 WDR35
3 skeletal muscle tissue development GO:0007519 9.49 MYF6 MYOD1
4 skeletal muscle cell differentiation GO:0035914 9.48 MYF6 MYOD1
5 intraciliary transport involved in cilium assembly GO:0035735 9.46 IFT122 WDR35
6 positive regulation of muscle cell differentiation GO:0051149 9.43 MYF6 MYOD1
7 protein localization to cilium GO:0061512 9.4 IFT122 WDR35
8 positive regulation of myoblast differentiation GO:0045663 9.37 MYF6 MYOD1
9 positive regulation of myoblast fusion GO:1901741 9.32 MYF6 MYOD1
10 intraciliary retrograde transport GO:0035721 9.26 IFT122 WDR35
11 positive regulation of skeletal muscle fiber development GO:0048743 9.16 MYF6 MYOD1
12 muscle organ development GO:0007517 9.13 FHL1 MYF6 MYOD1
13 muscle cell fate commitment GO:0042693 8.62 MYF6 MYOD1

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 8.96 MYF6 MYOD1
2 E-box binding GO:0070888 8.62 MYF6 MYOD1

Sources for Hemophagocytic Lymphohistiocytosis, Familial, 1

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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