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Type 3 autoimmune lymphoproliferative syndrome

MedGen UID:
274327
Concept ID:
C1519711
Disease or Syndrome
Synonyms: ALPS-Unknown Underlying Mutation; Autoimmune Lymphoproliferative Syndrome with Unknown Underlying Mutation; Autoimmune Lymphoproliferative Syndrome-Undetermined variant; Autoimmune Lymphoproliferative Syndrome-Unknown Underlying Mutation; Type 3 ALPS; Type 3 Autoimmune Lymphoproliferative Syndrome; type 3 autoimmune lymphoproliferative syndrome
 
Monarch Initiative: MONDO:8000023

Definition

A rare, primary immunodeficiency. It is caused by a currently undetermined defect in the Fas-induced apoptosis pathway. No mutations in Fas, FASLG or CASP10 are detectable. Disruption of Fas-induced apoptosis impairs lymphocyte homeostasis and immune tolerance. Characteristic laboratory findings include an increase in circulating, double-negative (CD4-/CD8-) T cells in the setting of immune-mediated anemia, thrombocytopenia and neutropenia. Clinical signs present in childhood include fatigue, pallor, bruising, hepatosplenomegaly and chronic, non-malignant, non-infectious lymphadenopathy. The clinical course is influenced by a strong association with other autoimmune disorders and an increased risk for developing Hodgkin and non-Hodgkin lymphoma. [from NCI]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVType 3 autoimmune lymphoproliferative syndrome

Recent clinical studies

Etiology

Andrews A, Maharaj A, Cottrell E, Chatterjee S, Shah P, Denvir L, Dumic K, Bossowski A, Mushtaq T, Vukovic R, Didi M, Shaw N, Metherell LA, Savage MO, Storr HL
J Clin Endocrinol Metab 2021 Oct 21;106(11):e4716-e4733. doi: 10.1210/clinem/dgab437. PMID: 34136918Free PMC Article
Slade CA, Bosco JJ, Binh Giang T, Kruse E, Stirling RG, Cameron PU, Hore-Lacy F, Sutherland MF, Barnes SL, Holdsworth S, Ojaimi S, Unglik GA, De Luca J, Patel M, McComish J, Spriggs K, Tran Y, Auyeung P, Nicholls K, O'Hehir RE, Hodgkin PD, Douglass JA, Bryant VL, van Zelm MC
Front Immunol 2018;9:694. Epub 2018 May 14 doi: 10.3389/fimmu.2018.00694. PMID: 29867917Free PMC Article
Gill K, Ghazinian H, Manch R, Gish R
Hepatol Int 2016 May;10(3):415-23. Epub 2015 Dec 10 doi: 10.1007/s12072-015-9684-3. PMID: 26660706Free PMC Article
Monti G, Saccardo F, Castelnovo L, Novati P, Sollima S, Riva A, Sarzi-Puttini P, Quartuccio L, De Vita S, Galli M
Autoimmun Rev 2014 Jun;13(6):609-14. Epub 2014 Jan 10 doi: 10.1016/j.autrev.2013.11.005. PMID: 24418294
Bloom AL
Mayo Clin Proc 1991 Jul;66(7):743-51. doi: 10.1016/s0025-6196(12)62088-6. PMID: 2072762

Diagnosis

Consonni F, Gambineri E, Favre C
Ann Hematol 2022 Mar;101(3):469-484. Epub 2022 Jan 20 doi: 10.1007/s00277-022-04761-7. PMID: 35059842Free PMC Article
Andrews A, Maharaj A, Cottrell E, Chatterjee S, Shah P, Denvir L, Dumic K, Bossowski A, Mushtaq T, Vukovic R, Didi M, Shaw N, Metherell LA, Savage MO, Storr HL
J Clin Endocrinol Metab 2021 Oct 21;106(11):e4716-e4733. doi: 10.1210/clinem/dgab437. PMID: 34136918Free PMC Article
Monti G, Saccardo F, Castelnovo L, Novati P, Sollima S, Riva A, Sarzi-Puttini P, Quartuccio L, De Vita S, Galli M
Autoimmun Rev 2014 Jun;13(6):609-14. Epub 2014 Jan 10 doi: 10.1016/j.autrev.2013.11.005. PMID: 24418294
Okazaki K, Uchida K, Koyabu M, Miyoshi H, Takaoka M
J Gastroenterol 2011 Mar;46(3):277-88. Epub 2011 Mar 11 doi: 10.1007/s00535-011-0386-x. PMID: 21452084
Ferri C
Orphanet J Rare Dis 2008 Sep 16;3:25. doi: 10.1186/1750-1172-3-25. PMID: 18796155Free PMC Article

Therapy

Mohamed MW, Al-Hammadi M, Hussein AM, Alarab D, Albreak HA, Tungekar MF, Dandi B
BMC Nephrol 2022 Mar 15;23(1):103. doi: 10.1186/s12882-022-02730-w. PMID: 35291980Free PMC Article
Gu H, Chen Z, Ma J, Wang J, Zhang R, Wu R, Wang T
Int J Immunopathol Pharmacol 2021 Jan-Dec;35:20587384211025934. doi: 10.1177/20587384211025934. PMID: 34187243Free PMC Article
Monti G, Saccardo F, Castelnovo L, Novati P, Sollima S, Riva A, Sarzi-Puttini P, Quartuccio L, De Vita S, Galli M
Autoimmun Rev 2014 Jun;13(6):609-14. Epub 2014 Jan 10 doi: 10.1016/j.autrev.2013.11.005. PMID: 24418294
Ferri C
Orphanet J Rare Dis 2008 Sep 16;3:25. doi: 10.1186/1750-1172-3-25. PMID: 18796155Free PMC Article
van der Werff Ten Bosch J, Schotte P, Ferster A, Azzi N, Boehler T, Laurey G, Arola M, Demanet C, Beyaert R, Thielemans K, Otten J
Br J Haematol 2002 Apr;117(1):176-88. doi: 10.1046/j.1365-2141.2002.03357.x. PMID: 11918552

Prognosis

Andrews A, Maharaj A, Cottrell E, Chatterjee S, Shah P, Denvir L, Dumic K, Bossowski A, Mushtaq T, Vukovic R, Didi M, Shaw N, Metherell LA, Savage MO, Storr HL
J Clin Endocrinol Metab 2021 Oct 21;106(11):e4716-e4733. doi: 10.1210/clinem/dgab437. PMID: 34136918Free PMC Article
Gill K, Ghazinian H, Manch R, Gish R
Hepatol Int 2016 May;10(3):415-23. Epub 2015 Dec 10 doi: 10.1007/s12072-015-9684-3. PMID: 26660706Free PMC Article
Ferri C
Orphanet J Rare Dis 2008 Sep 16;3:25. doi: 10.1186/1750-1172-3-25. PMID: 18796155Free PMC Article
Papiris SA, Tsonis IA, Moutsopoulos HM
Semin Respir Crit Care Med 2007 Aug;28(4):459-71. doi: 10.1055/s-2007-985667. PMID: 17764063
Müllauer L, Gruber P, Sebinger D, Buch J, Wohlfart S, Chott A
Mutat Res 2001 Jul;488(3):211-31. doi: 10.1016/s1383-5742(01)00057-6. PMID: 11397650

Clinical prediction guides

Galli M, Oreni L, Saccardo F, Castelnovo L, Filippini D, Marson P, Mascia MT, Mazzaro C, Origgi L, Ossi E, Pietrogrande M, Pioltelli P, Quartuccio L, Scarpato S, Sollima S, Riva A, Fraticelli P, Zani R, Giuggioli D, Sebastiani M, Sarzi Puttini P, Gabrielli A, Zignego AL, Scaini P, Ferri C, De Vita S, Monti G
Clin Exp Rheumatol 2017 Mar-Apr;35 Suppl 103(1):67-76. Epub 2017 Apr 19 PMID: 28466806
Maric I, Pittaluga S, Dale JK, Niemela JE, Delsol G, Diment J, Rosai J, Raffeld M, Puck JM, Straus SE, Jaffe ES
Am J Surg Pathol 2005 Jul;29(7):903-11. doi: 10.1097/01.pas.0000157997.61177.08. PMID: 15958855
van der Werff Ten Bosch J, Schotte P, Ferster A, Azzi N, Boehler T, Laurey G, Arola M, Demanet C, Beyaert R, Thielemans K, Otten J
Br J Haematol 2002 Apr;117(1):176-88. doi: 10.1046/j.1365-2141.2002.03357.x. PMID: 11918552
Müllauer L, Gruber P, Sebinger D, Buch J, Wohlfart S, Chott A
Mutat Res 2001 Jul;488(3):211-31. doi: 10.1016/s1383-5742(01)00057-6. PMID: 11397650
Bertolo F, De Vita S, Dolcetti R, Carbone A, Ferraccioli GF, Bartoli E, Boiocchi M
Clin Exp Rheumatol 1999 May-Jun;17(3):339-42. PMID: 10410268

Recent systematic reviews

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