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Thrombocytopenia, X-linked, with or without dyserythropoietic anemia(XLTDA)

MedGen UID:
763703
Concept ID:
C3550789
Disease or Syndrome
Synonym: XLTDA
 
Gene (location): GATA1 (Xp11.23)
 
Monarch Initiative: MONDO:0010308
OMIM®: 300367

Disease characteristics

Excerpted from the GeneReview: GATA1-Related Cytopenia
GATA1-related cytopenia is characterized by thrombocytopenia and/or anemia ranging from mild to severe. Thrombocytopenia typically presents in infancy as a bleeding disorder with easy bruising and mucosal bleeding (e.g., epistaxis). Anemia ranges from minimal (mild dyserythropoiesis) to severe (hydrops fetalis requiring in utero transfusion). At the extreme end of the clinical spectrum, severe hemorrhage and/or erythrocyte transfusion dependence are lifelong; at the milder end, anemia and the risk for bleeding may decrease spontaneously with age. One or more of the following may also be present: neutropenia, splenomegaly, cryptorchidism, hypospadias, and rarely additional clinical features of Diamond-Blackfan anemia. Heterozygous females may have mild-to-moderate symptoms such as menorrhagia. Rarely, GATA1-related cytopenia can progress to myelodysplastic syndrome or aplastic anemia. [from GeneReviews]
Authors:
Kaoru Takasaki  |  Melissa A Kacena  |  Wendy H Raskind, et. al.   view full author information

Additional descriptions

From OMIM
XLTDA is an X-linked recessive hematologic disorder characterized by thrombocytopenia and abnormal platelet morphology and function due to defective platelet maturation. Some patients have a variable severity of dyserythropoietic anemia (summary by Millikan et al., 2011).  http://www.omim.org/entry/300367
From MedlinePlus Genetics
Dyserythropoietic anemia and thrombocytopenia is a condition that affects blood cells and primarily occurs in males. A main feature of this condition is a type of anemia called dyserythropoietic anemia, which is characterized by a shortage of red blood cells. The term "dyserythropoietic" refers to the abnormal red blood cell formation that occurs in this condition. In affected individuals, immature red blood cells are unusually shaped and cannot develop into functional mature cells, leading to a shortage of healthy red blood cells. People with dyserythropoietic anemia and thrombocytopenia can have another blood disorder characterized by a reduced level of circulating platelets (thrombocytopenia). Platelets are cells that normally assist with blood clotting. Thrombocytopenia can cause easy bruising and abnormal bleeding. While people with dyserythropoietic anemia and thrombocytopenia can have signs and symptoms of both blood disorders, some are primarily affected by anemia, while others are more affected by thrombocytopenia.

The most severe cases of dyserythropoietic anemia and thrombocytopenia are characterized by hydrops fetalis, a condition in which excess fluid builds up in the body before birth. For many others, the signs and symptoms of dyserythropoietic anemia and thrombocytopenia begin in infancy. People with this condition experience prolonged bleeding or bruising after minor trauma or even in the absence of injury (spontaneous bleeding). Anemia can cause pale skin, weakness, and fatigue. Severe anemia may create a need for frequent blood transfusions to replenish the supply of red blood cells; however, repeated blood transfusions over many years can cause health problems such as excess iron in the blood. People with dyserythropoietic anemia and thrombocytopenia may also have a shortage of white blood cells (neutropenia), which can make them prone to recurrent infections. Additionally, they may have an enlarged spleen (splenomegaly). The severity of these abnormalities varies among affected individuals.

Some people with dyserythropoietic anemia and thrombocytopenia have additional blood disorders such as beta thalassemia or congenital erythropoietic porphyria. Beta thalassemia is a condition that reduces the production of hemoglobin, which is the iron-containing protein in red blood cells that carries oxygen. A decrease in hemoglobin can lead to a shortage of oxygen in cells and tissues throughout the body. Congenital erythropoietic porphyria is another disorder that impairs hemoglobin production. People with congenital erythropoietic porphyria are also very sensitive to sunlight, and areas of skin exposed to the sun can become fragile and blistered.  https://medlineplus.gov/genetics/condition/dyserythropoietic-anemia-and-thrombocytopenia

Clinical features

From HPO
Epistaxis
MedGen UID:
4996
Concept ID:
C0014591
Pathologic Function
Epistaxis, or nosebleed, refers to a hemorrhage localized in the nose.
Poikilocytosis
MedGen UID:
67451
Concept ID:
C0221281
Finding
The presence of abnormally shaped erythrocytes.
Congenital thrombocytopenia
MedGen UID:
124422
Concept ID:
C0272278
Disease or Syndrome
Thrombocytopenia with congenital onset.
Anemia of inadequate production
MedGen UID:
95937
Concept ID:
C0392708
Pathologic Function
A kind of anemia characterized by inadequate production of erythrocytes.
Acanthocytosis
MedGen UID:
195801
Concept ID:
C0687751
Disease or Syndrome
Acanthocytosis is a type of poikilocytosis characterized by the presence of spikes on the cell surface. The cells have an irregular shape resembling many-pointed stars.
Persistent bleeding after trauma
MedGen UID:
375403
Concept ID:
C1844374
Finding
Petechiae
MedGen UID:
10680
Concept ID:
C0031256
Disease or Syndrome
Petechiae are pinpoint-sized reddish/purple spots, resembling a rash, that appear just under the skin or a mucous membrane when capillaries have ruptured and some superficial bleeding into the skin has happened. This term refers to an abnormally increased susceptibility to developing petechiae.
Bruising susceptibility
MedGen UID:
140849
Concept ID:
C0423798
Finding
An ecchymosis (bruise) refers to the skin discoloration caused by the escape of blood into the tissues from ruptured blood vessels. This term refers to an abnormally increased susceptibility to bruising. The corresponding phenotypic abnormality is generally elicited on medical history as a report of frequent ecchymoses or bruising without adequate trauma.

Professional guidelines

PubMed

Koster MJ, Lasho TL, Olteanu H, Reichard KK, Mangaonkar A, Warrington KJ, Patnaik MM
Am J Hematol 2024 Feb;99(2):284-299. Epub 2023 Nov 11 doi: 10.1002/ajh.27156. PMID: 37950858
Cazzola M
Blood 2022 Apr 21;139(16):2460-2470. doi: 10.1182/blood.2021011045. PMID: 34932791
Palmer WC, Vishnu P, Sanchez W, Aqel B, Riegert-Johnson D, Seaman LAK, Bowman AW, Rivera CE
J Gen Intern Med 2018 Dec;33(12):2230-2236. Epub 2018 Sep 17 doi: 10.1007/s11606-018-4669-2. PMID: 30225768Free PMC Article

Recent clinical studies

Etiology

Gutierrez-Rodrigues F, Kusne Y, Fernandez J, Lasho T, Shalhoub R, Ma X, Alessi H, Finke C, Koster MJ, Mangaonkar A, Warrington KJ, Begna K, Xie Z, Ombrello AK, Viswanatha D, Ferrada M, Wilson L, Go R, Kourelis T, Reichard K, Olteanu H, Darden I, Hironaka D, Alemu L, Kajigaya S, Rosenzweig S, Calado RT, Groarke EM, Kastner DL, Calvo KR, Wu CO, Grayson PC, Young NS, Beck DB, Patel BA, Patnaik MM
Blood 2023 Jul 20;142(3):244-259. doi: 10.1182/blood.2022018774. PMID: 37084382Free PMC Article
Beck DB, Bodian DL, Shah V, Mirshahi UL, Kim J, Ding Y, Magaziner SJ, Strande NT, Cantor A, Haley JS, Cook A, Hill W, Schwartz AL, Grayson PC, Ferrada MA, Kastner DL, Carey DJ, Stewart DR
JAMA 2023 Jan 24;329(4):318-324. doi: 10.1001/jama.2022.24836. PMID: 36692560Free PMC Article
Iolascon A, Andolfo I, Russo R
Blood 2020 Sep 10;136(11):1274-1283. doi: 10.1182/blood.2019000948. PMID: 32702750
Rivers E, Worth A, Thrasher AJ, Burns SO
Br J Haematol 2019 May;185(4):647-655. Epub 2019 Mar 12 doi: 10.1111/bjh.15831. PMID: 30864154Free PMC Article
Galanello R, Origa R
Orphanet J Rare Dis 2010 May 21;5:11. doi: 10.1186/1750-1172-5-11. PMID: 20492708Free PMC Article

Diagnosis

Khitri MY, Hadjadj J, Mekinian A, Jachiet V
Joint Bone Spine 2024 Jul;91(4):105700. Epub 2024 Feb 1 doi: 10.1016/j.jbspin.2024.105700. PMID: 38307404
Iolascon A, Andolfo I, Russo R
Blood 2020 Sep 10;136(11):1274-1283. doi: 10.1182/blood.2019000948. PMID: 32702750
Rivers E, Worth A, Thrasher AJ, Burns SO
Br J Haematol 2019 May;185(4):647-655. Epub 2019 Mar 12 doi: 10.1111/bjh.15831. PMID: 30864154Free PMC Article
Massaad MJ, Ramesh N, Geha RS
Ann N Y Acad Sci 2013 May;1285:26-43. Epub 2013 Mar 25 doi: 10.1111/nyas.12049. PMID: 23527602
Galanello R, Origa R
Orphanet J Rare Dis 2010 May 21;5:11. doi: 10.1186/1750-1172-5-11. PMID: 20492708Free PMC Article

Therapy

Ferrada MA, Sikora KA, Luo Y, Wells KV, Patel B, Groarke EM, Ospina Cardona D, Rominger E, Hoffmann P, Le MT, Deng Z, Quinn KA, Rose E, Tsai WL, Wigerblad G, Goodspeed W, Jones A, Wilson L, Schnappauf O, Laird RS, Kim J, Allen C, Sirajuddin A, Chen M, Gadina M, Calvo KR, Kaplan MJ, Colbert RA, Aksentijevich I, Young NS, Savic S, Kastner DL, Ombrello AK, Beck DB, Grayson PC
Arthritis Rheumatol 2021 Oct;73(10):1886-1895. Epub 2021 Aug 31 doi: 10.1002/art.41743. PMID: 33779074
Rodeghiero F, Pecci A, Balduini CL
J Thromb Haemost 2018 Sep;16(9):1700-1710. Epub 2018 Jul 27 doi: 10.1111/jth.14217. PMID: 29956472
Iolascon A, Andolfo I, Barcellini W, Corcione F, Garçon L, De Franceschi L, Pignata C, Graziadei G, Pospisilova D, Rees DC, de Montalembert M, Rivella S, Gambale A, Russo R, Ribeiro L, Vives-Corrons J, Martinez PA, Kattamis A, Gulbis B, Cappellini MD, Roberts I, Tamary H; Working Study Group on Red Cells and Iron of the EHA
Haematologica 2017 Aug;102(8):1304-1313. Epub 2017 May 26 doi: 10.3324/haematol.2016.161166. PMID: 28550188Free PMC Article
Shwin KW, Lee CR, Goldbach-Mansky R
Dermatol Clin 2017 Jan;35(1):21-38. doi: 10.1016/j.det.2016.07.005. PMID: 27890235Free PMC Article
Bosticardo M, Ferrua F, Cavazzana M, Aiuti A
Curr Gene Ther 2014;14(6):413-21. doi: 10.2174/1566523214666140918103731. PMID: 25245089

Prognosis

Gutierrez-Rodrigues F, Kusne Y, Fernandez J, Lasho T, Shalhoub R, Ma X, Alessi H, Finke C, Koster MJ, Mangaonkar A, Warrington KJ, Begna K, Xie Z, Ombrello AK, Viswanatha D, Ferrada M, Wilson L, Go R, Kourelis T, Reichard K, Olteanu H, Darden I, Hironaka D, Alemu L, Kajigaya S, Rosenzweig S, Calado RT, Groarke EM, Kastner DL, Calvo KR, Wu CO, Grayson PC, Young NS, Beck DB, Patel BA, Patnaik MM
Blood 2023 Jul 20;142(3):244-259. doi: 10.1182/blood.2022018774. PMID: 37084382Free PMC Article
Obiorah IE, Patel BA, Groarke EM, Wang W, Trick M, Ombrello AK, Ferrada MA, Wu Z, Gutierrez-Rodrigues F, Lotter J, Wilson L, Hoffmann P, Cardona DO, Patel N, Dulau-Florea A, Kastner DL, Grayson PC, Beck DB, Young NS, Calvo KR
Blood Adv 2021 Aug 24;5(16):3203-3215. doi: 10.1182/bloodadvances.2021004976. PMID: 34427584Free PMC Article
Iolascon A, Russo R, Delaunay J
Curr Opin Hematol 2011 May;18(3):146-51. doi: 10.1097/MOH.0b013e32834521b0. PMID: 21378561
Galanello R, Origa R
Orphanet J Rare Dis 2010 May 21;5:11. doi: 10.1186/1750-1172-5-11. PMID: 20492708Free PMC Article
Wickramasinghe SN
Curr Opin Hematol 2000 Mar;7(2):71-8. doi: 10.1097/00062752-200003000-00001. PMID: 10698292

Clinical prediction guides

Beck DB, Bodian DL, Shah V, Mirshahi UL, Kim J, Ding Y, Magaziner SJ, Strande NT, Cantor A, Haley JS, Cook A, Hill W, Schwartz AL, Grayson PC, Ferrada MA, Kastner DL, Carey DJ, Stewart DR
JAMA 2023 Jan 24;329(4):318-324. doi: 10.1001/jama.2022.24836. PMID: 36692560Free PMC Article
Nunes-Santos CJ, Koh C, Rai A, Sacco K, Marciano BE, Kleiner DE, Marko J, Bergerson JRE, Stack M, Rivera MM, Constantine G, Strober W, Uzel G, Fuss IJ, Notarangelo LD, Holland SM, Rosenzweig SD, Heller T
J Allergy Clin Immunol 2022 Jan;149(1):400-409.e3. Epub 2021 Jun 1 doi: 10.1016/j.jaci.2021.05.028. PMID: 34087243Free PMC Article
Ferrada MA, Sikora KA, Luo Y, Wells KV, Patel B, Groarke EM, Ospina Cardona D, Rominger E, Hoffmann P, Le MT, Deng Z, Quinn KA, Rose E, Tsai WL, Wigerblad G, Goodspeed W, Jones A, Wilson L, Schnappauf O, Laird RS, Kim J, Allen C, Sirajuddin A, Chen M, Gadina M, Calvo KR, Kaplan MJ, Colbert RA, Aksentijevich I, Young NS, Savic S, Kastner DL, Ombrello AK, Beck DB, Grayson PC
Arthritis Rheumatol 2021 Oct;73(10):1886-1895. Epub 2021 Aug 31 doi: 10.1002/art.41743. PMID: 33779074
Denecke J, Marquardt T
Biochim Biophys Acta 2009 Sep;1792(9):915-20. Epub 2008 Dec 25 doi: 10.1016/j.bbadis.2008.12.005. PMID: 19150496
Marks PW, Mitus AJ
Am J Hematol 1996 Jan;51(1):55-63. doi: 10.1002/(SICI)1096-8652(199601)51:1<55::AID-AJH9>3.0.CO;2-6. PMID: 8571938

Recent systematic reviews

Park JH, Lee KH, Jeon B, Ochs HD, Lee JS, Gee HY, Seo S, Geum D, Piccirillo CA, Eisenhut M, van der Vliet HJ, Lee JM, Kronbichler A, Ko Y, Shin JI
Autoimmun Rev 2020 Jun;19(6):102526. Epub 2020 Mar 29 doi: 10.1016/j.autrev.2020.102526. PMID: 32234571

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