ORPHA:540
Familial hemophagocytic lymphohistiocytosis
Synonyms: Familial HLH
- Type
- Disease
- Group
- Disorder
- Inheritance
- Autosomal recessive
- Age of onset
- Adolescent, Infancy
- Status
- active
Familial Hemophagocytic lymphohistiocytosis (FHL) is a rare primary immunodeficiency characterized by a macrophage activation syndrome with an onset usually occurring within a few months or less common several years after birth.
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Names in Orphadata languages
12 of 12 languages| Lang | Name | Synonyms |
|---|---|---|
| en | Familial hemophagocytic lymphohistiocytosis | Familial HLH |
| fr | Lymphohistiocytose familiale | LHF · Lymphohistiocytose hémophagocytaire familiale |
| de | Lymphohistiozytose, hämophagozytische, familiäre Form | FHL |
| es | Linfohistiocitosis hemofagocítica familiar | LHH familiar |
| it | Linfoistiocitosi emofagocitica familiare | HLH familiare |
| nl | Familiale hemofagocytaire lymfohistiocytose | Familiale HLH |
| pt | Linfohistiocitose hemofagocítica familiar | |
| pl | Rodzinna limfohistiocytoza hemofagocytarna | Rodzinna HLH |
| cs | Familiární hemofagocytující lymfohistiocytóza | Familiární HLH |
| uk | Сімейний гемофагоцитарний лімфогістіоцитоз | Сімейна HLH |
| zh | 家族性嗜血细胞性淋巴组织细胞增多症 | 家族性嗜血细胞性淋巴组织细胞增多症 |
| tr | Ailesel hemofagositik lenfohistiyositoz | Ailesel HLH |
Definition in:
2
Cross-references
qualifier = Orphanet mapping relation| Source | Code | Qualifier | ICD relation | Validation |
|---|---|---|---|---|
| OMIM | 267700 | E | validated | |
| OMIM | 603552 | BTNT | validated | |
| OMIM | 603553 | BTNT | validated | |
| OMIM | 608898 | BTNT | validated | |
| OMIM | 613101 | BTNT | validated | |
| OMIM | 618998 | BTNT | not yet validated | |
| ICD-10 | D76.1 | NTBT | attributed | validated |
| ICD-11 | 4A01.23 | NTBT | index | validated |
| MONDO | 0015541 | E | validated | |
| MONDO | 15541 | E | validated | |
| UMLS | C0272199 | E | validated | |
| GARD | 6589 | E | validated | |
| MedDRA | 10070904 | E | validated |
E exact · NTBT this ORPHAcode is narrower than the target · BTNT broader than the target · ND not decided.
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Classification
Preferential parent (Orphanet linearisation):
Parents in the classifications (4):
- ORPHA:102005Brain inflammatory disease
rare neurological diseases - ORPHA:664450Inherited cancer-predisposing lymphoproliferative syndrome
rare genetic diseases; rare neoplastic diseases - ORPHA:664482Primary hemophagocytic lymphohistiocytosis without hypopigmentation
rare genetic diseases; rare immunological diseases; rare transplant-related disorders - ORPHA:717757Rare immune disease with inflammatory bowel disease
rare gastroenterological diseases; rare genetic diseases; rare transplant-related disorders
No children.
4
Genes
4 direct| Gene | Association | Status | HGNC | Ensembl | OMIM | Locus | Name | Source of validation |
|---|---|---|---|---|---|---|---|---|
| PRF1 | Disease-causing germline mutation(s) in | Assessed | HGNC:9360 | ENSG00000180644 | 170280 | 10q22.1 | perforin 1 | 11179007[PMID] |
| STX11 | Disease-causing germline mutation(s) in | Assessed | HGNC:11429 | ENSG00000135604 | 605014 | 6q24.2 | syntaxin 11 | 11179007[PMID] |
| STXBP2 | Disease-causing germline mutation(s) in | Assessed | HGNC:11445 | ENSG00000076944 | 601717 | 19p13.2 | syntaxin binding protein 2 | 11179007[PMID] |
| UNC13D | Disease-causing germline mutation(s) in | Assessed | HGNC:23147 | ENSG00000092929 | 608897 | 17q25.3 | unc-13 homolog D | 11179007[PMID] |
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Prevalence and incidence
3 records| Type | Class | Value | Area | Qualification | Validation | Source |
|---|---|---|---|---|---|---|
| Prevalence at birth | 1-9 / 100 000 | 2 / 100 000 | Sweden | Value and class | Validated | 9561910[PMID]_[EXPERT] |
| Point prevalence | Unknown | — | Worldwide | Class only | Not yet validated | ORPHANET |
| Annual incidence | 1-9 / 1 000 000 | 0.104 / 100 000 | China | Value and class | Validated | 34344437[PMID] |
Value is Orphadata's ValMoy: the mean estimate per 100 000 for prevalence and incidence, the number of cases or families for case reports.
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HPO phenotypes
45 annotations · validated 2021-06-30| HPO | Term (as annotated by Orphanet) | Diagnostic |
|---|---|---|
| Very frequent (99-80%) | ||
| HP:0012145 | Abnormality of multiple cell lineages in the bone marrow | |
| HP:0011112 | Abnormality of serum cytokine level | |
| HP:0011118 | Abnormality of tumor necrosis factor secretion | |
| HP:0001903 | Anemia | |
| HP:0002910 | Elevated circulating hepatic transaminase concentration | |
| HP:0001945 | Fever | |
| HP:0012156 | Hemophagocytosis | |
| HP:0003073 | Hypoalbuminemia | |
| HP:0002958 | Immune dysregulation | |
| HP:0003281 | Increased circulating ferritin concentration | |
| HP:0030356 | Increased serum interferon-gamma level | |
| HP:0001873 | Thrombocytopenia | |
| Frequent (79-30%) | ||
| HP:0012177 | Abnormal natural killer cell physiology | |
| HP:0012211 | Abnormal renal physiology | |
| HP:0011121 | Abnormal skin morphology | |
| HP:0003256 | Abnormality of the coagulation cascade | |
| HP:0002086 | Abnormality of the respiratory system | |
| HP:0012229 | CSF pleocytosis | |
| HP:0002611 | Cholestatic liver disease | |
| HP:0001410 | Decreased liver function | |
| HP:0001875 | Decreased total neutrophil count | |
| HP:0031364 | Ecchymosis | |
| HP:0001019 | Erythroderma | |
| HP:0002240 | Hepatomegaly | |
| HP:0002155 | Hypertriglyceridemia | |
| HP:0011900 | Hypofibrinogenemia | |
| HP:0030783 | Increased circulating interleukin 6 concentration | |
| HP:0002716 | Lymphadenopathy | |
| HP:0000967 | Petechiae | |
| HP:0000979 | Purpura | |
| HP:0000988 | Skin rash | |
| HP:0001744 | Splenomegaly | |
| Occasional (29-5%) | ||
| HP:0002500 | Abnormal cerebral white matter morphology | |
| HP:0000707 | Abnormality of the nervous system | |
| HP:0000978 | Bruising susceptibility | |
| HP:0002583 | Colitis | |
| HP:0001259 | Coma | |
| HP:0004313 | Decreased circulating antibody level | |
| HP:0004302 | Functional motor deficit | |
| HP:0002383 | Infectious encephalitis | |
| HP:0000952 | Jaundice | |
| HP:0040186 | Maculopapular exanthema | |
| HP:0009830 | Peripheral neuropathy | |
| HP:0001250 | Seizure | |
| Very rare (<4-1%) | ||
| HP:0000407 | Sensorineural hearing impairment | |
Run the differential on the 12 obligate / very frequent terms
Annotation source: 26461150[PMID]_32387063[PMID]_28934563[PMID]
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Sources for this card
- Orphanet page: orpha.net/en/disease/detail/540
- This record as JSON: /data/d/540.json