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Amegakaryocytic thrombocytopenia, congenital, 2(CAMT2)

MedGen UID:
1848998
Concept ID:
C5882679
Disease or Syndrome
Synonym: CAMT2
 
Gene (location): THPO (3q27.1)
 
Monarch Initiative: MONDO:0957575
OMIM®: 620481

Definition

Congenital amegakaryocytic thrombocytopenia-2 (CAMT2) is an autosomal recessive disorder characterized by thrombocytopenia with progression to pancytopenia, aplastic anemia, and bone marrow failure. Serum THPO is decreased or inappropriately normal, and bone marrow is hypocellular with decreased or absent megakaryocytes. Most patients present in infancy or early childhood and have a severe disease course, whereas some have later onset and milder symptoms. Bone marrow transplant is ineffective because the defect is extrinsic to hematopoietic cells. Treatment with THPO receptor (MPL; 159530) agonists results in clinical improvement and restoration of trilineage hematopoiesis (Dasouki et al., 2013; Seo et al., 2017). For a discussion of genetic heterogeneity of CAMT, see CAMT1 (604498). [from OMIM]

Clinical features

From HPO
Anemia
MedGen UID:
1526
Concept ID:
C0002871
Disease or Syndrome
A reduction in erythrocytes volume or hemoglobin concentration.
Aplastic anemia
MedGen UID:
8063
Concept ID:
C0002874
Disease or Syndrome
Aplastic anemia is a serious disorder of the bone marrow that affects between 2 and 5 persons per million per year. About 75% of these cases are classified as idiopathic (Young, 2000). In about 15% of cases a drug or infection can be identified that precipitates the aplasia, although why only some individuals are susceptible is unclear. In about 5 to 10% of patients, the aplastic anemia is constitutional--i.e., is familial or presents with one or more associated somatic abnormalities (summary by Vulliamy et al., 2002).
Pancytopenia
MedGen UID:
18281
Concept ID:
C0030312
Disease or Syndrome
An abnormal reduction in numbers of all blood cell types (red blood cells, white blood cells, and platelets).
Thrombocytopenia
MedGen UID:
52737
Concept ID:
C0040034
Disease or Syndrome
A reduction in the number of circulating thrombocytes.
Bone marrow hypocellularity
MedGen UID:
383749
Concept ID:
C1855710
Finding
A reduced number of hematopoietic cells present in the bone marrow relative to marrow fat.
Neutropenia
MedGen UID:
163121
Concept ID:
C0853697
Finding
An abnormally low number of neutrophils in the peripheral blood.
Elevated circulating alpha-fetoprotein concentration
MedGen UID:
65916
Concept ID:
C0235971
Finding
Concentration of alpha-fetoprotein in the blood circulation above the upper limit of normal.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

Professional guidelines

PubMed

Geddis AE
Int J Lab Hematol 2013 Feb;35(1):14-25. Epub 2012 Jul 30 doi: 10.1111/j.1751-553X.2012.01454.x. PMID: 22846067

Recent clinical studies

Etiology

Cancio M, Hebert K, Kim S, Aljurf M, Olson T, Anderson E, Burroughs L, Vatsayan A, Myers K, Hashem H, Hanna R, Horn B, Prestidge T, Boelens JJ, Boulad F, Eapen M
Transplant Cell Ther 2022 Feb;28(2):101.e1-101.e6. Epub 2021 Oct 17 doi: 10.1016/j.jtct.2021.10.009. PMID: 34670170Free PMC Article
Ahmed IA, Farooqi MS, Vander Lugt MT, Boklan J, Rose M, Friehling ED, Triplett B, Lieuw K, Saldana BD, Smith CM, Schwartz JR, Goyal RK
Biol Blood Marrow Transplant 2019 Nov;25(11):2186-2196. Epub 2019 Jul 12 doi: 10.1016/j.bbmt.2019.07.007. PMID: 31306780Free PMC Article
Babushok DV, Bessler M
Best Pract Res Clin Haematol 2015 Mar;28(1):55-68. Epub 2014 Nov 12 doi: 10.1016/j.beha.2014.11.004. PMID: 25659730Free PMC Article
Tamary H, Alter BP
Pediatr Hematol Oncol 2007 Mar;24(2):87-99. doi: 10.1080/08880010601123240. PMID: 17454774
Steele M, Hitzler J, Doyle JJ, Germeshausen M, Fernandez CV, Yuille K, Dror Y
Pediatr Blood Cancer 2005 Aug;45(2):212-6. doi: 10.1002/pbc.20332. PMID: 15782403

Diagnosis

Germeshausen M, Ballmaier M
Best Pract Res Clin Haematol 2021 Jun;34(2):101286. Epub 2021 Jul 14 doi: 10.1016/j.beha.2021.101286. PMID: 34404532
Germeshausen M, Ballmaier M
Haematologica 2021 Sep 1;106(9):2439-2448. doi: 10.3324/haematol.2020.257972. PMID: 32703794Free PMC Article
Babushok DV, Bessler M
Best Pract Res Clin Haematol 2015 Mar;28(1):55-68. Epub 2014 Nov 12 doi: 10.1016/j.beha.2014.11.004. PMID: 25659730Free PMC Article
Geddis AE
Pediatr Blood Cancer 2011 Aug;57(2):199-203. Epub 2011 Feb 18 doi: 10.1002/pbc.22927. PMID: 21337678
Geddis AE
Hematol Oncol Clin North Am 2009 Apr;23(2):321-31. doi: 10.1016/j.hoc.2009.01.012. PMID: 19327586Free PMC Article

Therapy

Bayegi SN, Hamidieh AA, Behfar M, Saghazadeh A, Bozorgmehr M, Tajik N, Delbandi AA, Delavari S, Shekarabi M, Rezaei N
Endocr Metab Immune Disord Drug Targets 2024;24(2):265-272. doi: 10.2174/1871530323666230801100113. PMID: 37526450
Cancio M, Hebert K, Kim S, Aljurf M, Olson T, Anderson E, Burroughs L, Vatsayan A, Myers K, Hashem H, Hanna R, Horn B, Prestidge T, Boelens JJ, Boulad F, Eapen M
Transplant Cell Ther 2022 Feb;28(2):101.e1-101.e6. Epub 2021 Oct 17 doi: 10.1016/j.jtct.2021.10.009. PMID: 34670170Free PMC Article
Babushok DV, Bessler M
Best Pract Res Clin Haematol 2015 Mar;28(1):55-68. Epub 2014 Nov 12 doi: 10.1016/j.beha.2014.11.004. PMID: 25659730Free PMC Article
Ueki H, Maeda N, Sekimizu M, Tsukushi S, Nishida Y, Horibe K
J Pediatr Hematol Oncol 2013 Mar;35(2):134-8. doi: 10.1097/MPH.0b013e3182677f19. PMID: 22995925
Al-Ahmari A, Ayas M, Al-Jefri A, Al-Mahr M, Rifai S, El-Solh H
Bone Marrow Transplant 2004 Apr;33(8):829-31. doi: 10.1038/sj.bmt.1704445. PMID: 14968137

Prognosis

Germeshausen M, Ballmaier M
Haematologica 2021 Sep 1;106(9):2439-2448. doi: 10.3324/haematol.2020.257972. PMID: 32703794Free PMC Article
Ahmed IA, Farooqi MS, Vander Lugt MT, Boklan J, Rose M, Friehling ED, Triplett B, Lieuw K, Saldana BD, Smith CM, Schwartz JR, Goyal RK
Biol Blood Marrow Transplant 2019 Nov;25(11):2186-2196. Epub 2019 Jul 12 doi: 10.1016/j.bbmt.2019.07.007. PMID: 31306780Free PMC Article
Lin Q, Zhang Y, Zhou R, Zheng Y, Zhao L, Huang M, Zhang X, Leung AYH, Zhang W, Zhang Y
Leukemia 2017 May;31(5):1206-1216. Epub 2016 Nov 4 doi: 10.1038/leu.2016.320. PMID: 27811851
Geddis AE
Hematol Oncol Clin North Am 2009 Apr;23(2):321-31. doi: 10.1016/j.hoc.2009.01.012. PMID: 19327586Free PMC Article
Tefferi A
Leuk Lymphoma 2008 Mar;49(3):388-97. doi: 10.1080/10428190801895360. PMID: 18297515

Clinical prediction guides

Bayegi SN, Hamidieh AA, Behfar M, Saghazadeh A, Bozorgmehr M, Tajik N, Delbandi AA, Delavari S, Shekarabi M, Rezaei N
Endocr Metab Immune Disord Drug Targets 2024;24(2):265-272. doi: 10.2174/1871530323666230801100113. PMID: 37526450
Deliloğlu B, Tüfekçi Ö, Tüzün F, Aykut A, Ceylan Eİ, Durmaz A, Yılmaz Ş, Duman N, Özkan H, Ören H
Turk J Pediatr 2022;64(4):736-740. doi: 10.24953/turkjped.2021.4855. PMID: 36082647
Gasior Kabat M, Bueno D, Sisinni L, De Paz R, Mozo Y, Perona R, Arias-Salgado EG, Rosich B, Marcos A, Romero AB, Constanzo A, Jiménez-Yuste V, Pérez-Martínez A
Int J Hematol 2021 Jul;114(1):116-123. Epub 2021 Mar 27 doi: 10.1007/s12185-021-03138-2. PMID: 33772729
Germeshausen M, Ancliff P, Estrada J, Metzler M, Ponstingl E, Rütschle H, Schwabe D, Scott RH, Unal S, Wawer A, Zeller B, Ballmaier M
Blood Adv 2018 Mar 27;2(6):586-596. doi: 10.1182/bloodadvances.2018016501. PMID: 29540340Free PMC Article
Freedman MH, Estrov Z
Am J Pediatr Hematol Oncol 1990 Summer;12(2):225-30. PMID: 2378417

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