KEGG   DISEASE: Familial hemophagocytic lymphohistiocytosis
Entry
H00109                      Disease                                
Name
Familial hemophagocytic lymphohistiocytosis
  Supergrp
Disorders of adaptive immunity [DS:H02526]
Primary immunodeficiency disease [DS:H01725]
Description
Familial hemophagocytic lymphohistiocytosis (FHL) is an autosomal recessive disorder with uncontrolled activation of T cells and macrophages (hemophagocytic activation) that infiltrate into liver, spleen, bone marrow, and CNS. The symptoms include fever, hepatosplenomegaly, and cytopenia. Homozygous and heterozygous gene mutations of perforin, the major immune cytotoxic protein, were detected with frequency between 15% and 50% of all FHPL patients. UNC13D is the second gene associated with FHPL. The encoded protein (Munc13-4) is important for cytolytic granule exocytosis. Recently a third FHPL associated gene on chromosome 6q24 with mutations in STX11 was identified. The encoded protein, t-SNARE syntaxin 11, also plays a role in intracellular trafficking, but its precise role is not known.
Category
Primary immunodeficiency
Brite
Human diseases [BR:br08402]
 Immune system diseases
  Primary immunodeficiency
   H00109  Familial hemophagocytic lymphohistiocytosis
Human diseases in ICD-11 classification [BR:br08403]
 04 Diseases of the immune system
  Primary immunodeficiencies
   4A01  Primary immunodeficiencies due to disorders of adaptive immunity
    H00109  Familial hemophagocytic lymphohistiocytosis
Related
pathway
hsa04130  SNARE interactions in vesicular transport
Gene
(FHL2) PRF1 [HSA:5551] [KO:K07818]
(FHL3) UNC13D [HSA:201294] [KO:K19728]
(FHL4) STX11 [HSA:8676] [KO:K08487]
(FHL5) STXBP2 [HSA:6813] [KO:K15300]
(FHL6) RC3H1 [HSA:149041] [KO:K15690]
Drug
Emapalumab [DR:D11120]
Other DBs
ICD-11: 4A01.23
ICD-10: D76.1
MeSH: D056735
OMIM: 267700 603553 608898 603552 613101 618998
Reference
PMID:16304363 (FHL2, FHL3, FHL4)
  Authors
Janka G, zur Stadt U
  Title
Familial and acquired hemophagocytic lymphohistiocytosis.
  Journal
Hematology Am Soc Hematol Educ Program 82-8 (2005)
DOI:10.1182/asheducation-2005.1.82
Reference
PMID:17162365 (FHL2, FHL3, FHL4)
  Authors
Kumar A, Teuber SS, Gershwin ME.
  Title
Current perspectives on primary immunodeficiency diseases.
  Journal
Clin Dev Immunol 13:223-59 (2006)
DOI:10.1080/17402520600800705
Reference
PMID:17952897 (FHL2, FHL3, FHL4)
  Authors
Geha RS, Notarangelo LD, Casanova JL, Chapel H, Conley ME, Fischer A, Hammarstrom L, Nonoyama S, Ochs HD, Puck JM, Roifman C, Seger R, Wedgwood J.
  Title
Primary immunodeficiency diseases: an update from the International Union of Immunological Societies Primary Immunodeficiency Diseases Classification Committee.
  Journal
J Allergy Clin Immunol 120:776-94 (2007)
DOI:10.1016/j.jaci.2007.08.053
Reference
PMID:20798128 (FHL5)
  Authors
Cetica V, Santoro A, Gilmour KC, Sieni E, Beutel K, Pende D, Marcenaro S, Koch F, Grieve S, Wheeler R, Zhao F, zur Stadt U, Griffiths GM, Arico M
  Title
STXBP2 mutations in children with familial haemophagocytic lymphohistiocytosis type 5.
  Journal
J Med Genet 47:595-600 (2010)
DOI:10.1136/jmg.2009.075341
Reference
PMID:31636267 (FHL6)
  Authors
Tavernier SJ, Athanasopoulos V, Verloo P, Behrens G, Staal J, Bogaert DJ, Naesens L, De Bruyne M, Van Gassen S, Parthoens E, Ellyard J, Cappello J, Morris LX, Van Gorp H, Van Isterdael G, Saeys Y, Lamkanfi M, Schelstraete P, Dehoorne J, Bordon V, Van Coster R, Lambrecht BN, Menten B, Beyaert R, Vinuesa CG, Heissmeyer V, Dullaers M, Haerynck F
  Title
A human immune dysregulation syndrome characterized by severe hyperinflammation with a homozygous nonsense Roquin-1 mutation.
  Journal
Nat Commun 10:4779 (2019)
DOI:10.1038/s41467-019-12704-6
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