{"orpha":306550,"name":"FADD-related immunodeficiency","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":[],"definition":"FADD-related immunodeficiency is a rare genetic immunological disease reported in a single consanguineous Pakistani family with several affected members presenting with severe bacterial and viral infections, recurrent hepatopathy (portal inflammation, fibrosis), and recurrent, stereotypical febrile episodes, sometimes lasting several days, with encephalopathy and difficult-to-control seizures. Variable cardiac malformations were also reported. Although there were autoimmune lymphoproliferative syndrome (ALPS)-like biological features, clinical ALPS was not present. A homozygous missense mutation in the <i>FADD</i> gene (11q13.3) was found in the family and the disease is thought to follow an autosomal recessive pattern of inheritance.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-306550/","orphanet_url":"https://www.orpha.net/en/disease/detail/306550","names":{"fr":{"name":"Déficit immunitaire lié à FADD","definition":"Maladie immunologique génétique rare rapportée dans une seule famille pakistanaise consanguine dont plusieurs membres atteints présentent des infections bactériennes et virales sévères, une hépatopathie récurrente (inflammation portale, fibrose) et des épisodes fébriles récidivants et stéréotypés, parfois d'une durée de plusieurs jours, accompagnés d'encéphalopathie et de convulsions difficiles à contrôler. Des malformations cardiaques variables ont également été rapportées. Bien que des caractéristiques biologiques similaires à celles du syndrome lymphoprolifératif auto-immun (ALPS) aient été observées, aucun signe clinique d'ALPS n'était présent. Une mutation homozygote faux-sens a été identifiée dans le gène <i>FADD</i> (11q13.3) au sein de la famille et la maladie semble suivre un mode de transmission autosomique récessif."},"de":{"name":"FADD-abhängiger Immundefekt"},"es":{"name":"Inmunodeficiencia asociada al gen FADD","definition":"Es una enfermedad inmunológica genética y poco frecuente descrita en una única familia consanguínea Pakistaní con varios miembros afectados. Se manifiesta con graves infecciones bacterianas y víricas, hepatopatía recurrente (inflamación portal, fibrosis), y episodios recurrentes febriles típicos, en ocasiones durante varios días, con encefalopatía y convulsiones difíciles de controlar. También se han descrito malformaciones cardiacas variables. A pesar de tratarse de síntomas similares a los del síndrome linfoproliferativo autoinmune (SLPA), no se observó el SLPA clínico. En esta familia, se encontró una mutación en homocigosis con cambio de sentido en el gen <i>FADD</i> (11q13.3) y se sospecha que la enfermedad sigue un patrón de herencia autosómico recesivo."},"it":{"name":"Immunodeficienza FADD-correlata","definition":"L'immunodeficienza correlata al gene FADD è una malattia immunologica genetica rara, descritta in una sola famiglia consanguinea pachistana, che aveva più membri affetti, che presentavano infezioni batteriche e virali gravi, epatopatia ricorrente (infiammazione portale, fibrosi) ed episodi febbrili stereotipati e recidivanti, che potevano durare diversi giorni, associati ad encefalopatia e crisi epilettiche difficili da controllare. Sono state descritte anche vari difetti cardiaci. Anche se coesistevano alcune caratteristiche biologiche della pseudo-sindrome linfoproliferativa autoimmune (ALPS), questa malattia non era presente. Nella famiglia è stata individuata una mutazione missenso omozigote nel gene FADD (11q13.3). Si ritiene che la malattia abbia una trasmissione autosomica recessiva."},"nl":{"name":"FADD-gerelateerde immuundeficiëntie","definition":"FADD-gerelateerde immuundeficiëntie is een zeldzame genetische immunologische ziekte en werd gerapporteerd bij één enkele bloedverwante Pakistaanse familie met meerdere getroffen familieleden, die ernstige bacteriële en virale infecties, terugkerende hepatopathie (inflammatie van de poortader, fibrose), en terugkerende, stereotype febriele episodes, soms met een duur van meerdere dagen, met encefalopathie en moeilijk te controleren insulten vertonen. Variabele hartmalformaties werden ook gerapporteerd. Hoewel auto-immuun lymfoproliferatief syndroom (ALPS)-achtige biologische kenmerken werden waargenomen, was klinisch ALPS niet aanwezig. Er werd een homozygote missense mutatie in het gen <i>FADD</i> (11q13.3) aangetroffen bij de familie en de ziekte volgt vermoedelijk een autosomaal recessief overervingspatroon."},"pt":{"name":"Imunodeficiência FADD-relacionada"},"pl":{"name":"Niedobór odporności zwiazany z FADD"},"cs":{"name":"FADD-vázaná imunodeficience"},"uk":{"name":"Імунодефіцит, повязаний з FADD","definition":"FADD-related immunodeficiency is a rare genetic immunological disease reported in a single consanguineous Pakistani family with several affected members presenting with severe bacterial and viral infections, recurrent hepatopathy (portal inflammation, fibrosis), and recurrent, stereotypical febrile episodes, sometimes lasting several days, with encephalopathy and difficult-to-control seizures. Variable cardiac malformations were also reported. Although there were autoimmune lymphoproliferative syndrome (ALPS)-like biological features, clinical ALPS was not present. A homozygous missense mutation in the <i>FADD</i> gene (11q13.3) was found in the family and the disease is thought to follow an autosomal recessive pattern of inheritance."},"zh":{"name":"FADD基因相关免疫缺陷","definition":"FADD相关免疫缺陷是一种罕见的遗传性免疫疾病，在一个近亲巴基斯坦家系中，几个受累成员表现为严重细菌和病毒感染、复发性肝病（门脉炎症、纤维化）和反复发热，持续数天，伴脑病和难以控制的惊厥发作。也有报道多种心脏畸形。虽然有自身免疫性淋巴增生综合征（ALPS）样特征，但临床上无ALPS。该家系中发现FADD基因（11q13.3）纯合错义突变，为常染色体隐性遗传模式。"},"tr":{"name":"FADD-ilişkili immün yetmezlik"}},"xrefs":[{"source":"OMIM","code":"613759","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"D89.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"4A01.21","qualifier":"NTBT","icd_relation":"index","validated":true,"icd11_uri":"440676168"},{"source":"MONDO","code":"0013408","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C4509831","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":98004,"name":"Rare immune disease"},"parents":[{"orpha":169355,"name":"Immunodeficiency syndrome with autoimmunity","classifications":[156,195,233]},{"orpha":664450,"name":"Inherited cancer-predisposing lymphoproliferative syndrome","classifications":[156,202]}],"children":[],"genes":[{"symbol":"FADD","name":"Fas associated via death domain","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"21109225[PMID]","hgnc":"3573","ensembl":"ENSG00000168040","omim":"602457","loci":["11q13.3"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Infancy","Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":4.0,"area":"Worldwide","status":"Validated","source":"21109225[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_21109225[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2017-04-11","source":"21109225[PMID]","terms":[{"hpo":"HP:0001410","label":"Decreased liver function","frequency":"Obligate (100%)","criteria":null},{"hpo":"HP:0001298","label":"Encephalopathy","frequency":"Obligate (100%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Obligate (100%)","criteria":null},{"hpo":"HP:0002059","label":"Cerebral atrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001395","label":"Hepatic fibrosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0030057","label":"Autoimmune antibody positivity","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0004935","label":"Pulmonary artery atresia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001629","label":"Ventricular septal defect","frequency":"Occasional (29-5%)","criteria":null}]}}