{"orpha":540,"name":"Familial hemophagocytic lymphohistiocytosis","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["Familial HLH"],"definition":"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.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-540/","orphanet_url":"https://www.orpha.net/en/disease/detail/540","names":{"fr":{"name":"Lymphohistiocytose familiale","synonyms":["LHF","Lymphohistiocytose hémophagocytaire familiale"],"definition":"La lymphohistiocytose familiale (LHF) est un déficit immunitaire primaire caractérisé par un syndrome d'activation macrophagique avec un début dans les premiers mois de vie ou plus rarement plusieurs années après la naissance."},"de":{"name":"Lymphohistiozytose, hämophagozytische, familiäre Form","synonyms":["FHL"],"definition":"Die familiäre hämophagozytische Lymphohistiozytose (FHL) ist ein seltener primärer Immundefekt, der durch ein Makrophagen-Aktivierungssyndrom (siehe dort) gekennzeichnet ist und in der Regel innerhalb weniger Monate oder seltener mehrere Jahre nach der Geburt auftritt."},"es":{"name":"Linfohistiocitosis hemofagocítica familiar","synonyms":["LHH familiar"],"definition":"Es una inmunodeficiencia primaria poco común caracterizada por un síndrome de activación de macrófagos que suele debutar a los pocos meses de edad o, con menor frecuencia, varios años después del nacimiento."},"it":{"name":"Linfoistiocitosi emofagocitica familiare","synonyms":["HLH familiare"]},"nl":{"name":"Familiale hemofagocytaire lymfohistiocytose","synonyms":["Familiale HLH"],"definition":"Familiale hemofagocytische lymfohistiocytose (FHL) is een zeldzame primaire immuundeficiëntie die wordt gekarakteriseerd door een macrofaag-activatie syndroom (zie deze term) en doorgaans optreedt binnen enkele maanden, of minder gebruikelijk binnen een aantal jaren, na de geboorte."},"pt":{"name":"Linfohistiocitose hemofagocítica familiar"},"pl":{"name":"Rodzinna limfohistiocytoza hemofagocytarna","synonyms":["Rodzinna HLH"]},"cs":{"name":"Familiární hemofagocytující lymfohistiocytóza","synonyms":["Familiární HLH"]},"uk":{"name":"Сімейний гемофагоцитарний лімфогістіоцитоз","synonyms":["Сімейна HLH"],"definition":"Familial Hemophagocytic lymphohistiocytosis (FHL) is a rare primary immunodeficiency characterized by a macrophage activation syndrome (see this term) with an onset usually occurring within a few months or less common several years after birth."},"zh":{"name":"家族性嗜血细胞性淋巴组织细胞增多症","synonyms":["家族性嗜血细胞性淋巴组织细胞增多症"]},"tr":{"name":"Ailesel hemofagositik lenfohistiyositoz","synonyms":["Ailesel HLH"]}},"xrefs":[{"source":"OMIM","code":"267700","qualifier":"E","icd_relation":null,"validated":true},{"source":"OMIM","code":"603552","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"603553","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"608898","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"613101","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"618998","qualifier":"BTNT","icd_relation":null,"validated":false},{"source":"ICD-10","code":"D76.1","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"4A01.23","qualifier":"NTBT","icd_relation":"index","validated":true,"icd11_uri":"950019605"},{"source":"MONDO","code":"0015541","qualifier":"E","icd_relation":null,"validated":true},{"source":"MONDO","code":"15541","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C0272199","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"6589","qualifier":"E","icd_relation":null,"validated":true},{"source":"MedDRA","code":"10070904","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":98004,"name":"Rare immune disease"},"parents":[{"orpha":102005,"name":"Brain inflammatory disease","classifications":[181]},{"orpha":664450,"name":"Inherited cancer-predisposing lymphoproliferative syndrome","classifications":[156,202]},{"orpha":664482,"name":"Primary hemophagocytic lymphohistiocytosis without hypopigmentation","classifications":[156,195,233]},{"orpha":717757,"name":"Rare immune disease with inflammatory bowel disease","classifications":[152,156,233]}],"children":[],"genes":[{"symbol":"PRF1","name":"perforin 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"11179007[PMID]","hgnc":"9360","ensembl":"ENSG00000180644","omim":"170280","loci":["10q22.1"]},{"symbol":"STX11","name":"syntaxin 11","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"11179007[PMID]","hgnc":"11429","ensembl":"ENSG00000135604","omim":"605014","loci":["6q24.2"]},{"symbol":"STXBP2","name":"syntaxin binding protein 2","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"11179007[PMID]","hgnc":"11445","ensembl":"ENSG00000076944","omim":"601717","loci":["19p13.2"]},{"symbol":"UNC13D","name":"unc-13 homolog D","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"11179007[PMID]","hgnc":"23147","ensembl":"ENSG00000092929","omim":"608897","loci":["17q25.3"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Adolescent","Infancy"],"prevalence":[{"type":"Prevalence at birth","qualification":"Value and class","class":"1-9 / 100 000","value":2.0,"area":"Sweden","status":"Validated","source":"9561910[PMID]_[EXPERT]"},{"type":"Point prevalence","qualification":"Class only","class":"Unknown","value":0.0,"area":"Worldwide","status":"Not yet validated","source":"ORPHANET"},{"type":"Annual incidence","qualification":"Value and class","class":"1-9 / 1 000 000","value":0.104,"area":"China","status":"Validated","source":"34344437[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2021-06-30","source":"26461150[PMID]_32387063[PMID]_28934563[PMID]","terms":[{"hpo":"HP:0012145","label":"Abnormality of multiple cell lineages in the bone marrow","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0011112","label":"Abnormality of serum cytokine level","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0011118","label":"Abnormality of tumor necrosis factor secretion","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001903","label":"Anemia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002910","label":"Elevated circulating hepatic 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(79-30%)","criteria":null},{"hpo":"HP:0002240","label":"Hepatomegaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002155","label":"Hypertriglyceridemia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011900","label":"Hypofibrinogenemia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0030783","label":"Increased circulating interleukin 6 concentration","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002716","label":"Lymphadenopathy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000967","label":"Petechiae","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000979","label":"Purpura","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000988","label":"Skin rash","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001744","label":"Splenomegaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002500","label":"Abnormal cerebral white matter morphology","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000707","label":"Abnormality of the nervous system","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000978","label":"Bruising susceptibility","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002583","label":"Colitis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001259","label":"Coma","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0004313","label":"Decreased circulating antibody level","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0004302","label":"Functional motor deficit","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002383","label":"Infectious encephalitis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000952","label":"Jaundice","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0040186","label":"Maculopapular exanthema","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0009830","label":"Peripheral neuropathy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000407","label":"Sensorineural hearing impairment","frequency":"Very rare (<4-1%)","criteria":null}]}}