KEGG   DISEASE: Familial hemophagocytic lymphohistiocytosis
H00109                      Disease                                
Familial hemophagocytic lymphohistiocytosis
Disorders of adaptive immunity [DS:H02526]
Primary immunodeficiency disease [DS:H01725]
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.
Primary immunodeficiency
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
hsa04130  SNARE interactions in vesicular transport
(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]
Emapalumab [DR:D11120]
Other DBs
ICD-11: 4A01.23
ICD-10: D76.1
MeSH: D056735
OMIM: 267700 603553 608898 603552 613101 618998
PMID:16304363 (FHL2, FHL3, FHL4)
Janka G, zur Stadt U
Familial and acquired hemophagocytic lymphohistiocytosis.
Hematology Am Soc Hematol Educ Program 82-8 (2005)
PMID:17162365 (FHL2, FHL3, FHL4)
Kumar A, Teuber SS, Gershwin ME.
Current perspectives on primary immunodeficiency diseases.
Clin Dev Immunol 13:223-59 (2006)
PMID:17952897 (FHL2, FHL3, FHL4)
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.
Primary immunodeficiency diseases: an update from the International Union of Immunological Societies Primary Immunodeficiency Diseases Classification Committee.
J Allergy Clin Immunol 120:776-94 (2007)
PMID:20798128 (FHL5)
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
STXBP2 mutations in children with familial haemophagocytic lymphohistiocytosis type 5.
J Med Genet 47:595-600 (2010)
PMID:31636267 (FHL6)
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
A human immune dysregulation syndrome characterized by severe hyperinflammation with a homozygous nonsense Roquin-1 mutation.
Nat Commun 10:4779 (2019)

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