Thalassemias
Authors:
L. Sulovská 1; M. Divoká 2; D. Pospíšilová 1
Authors‘ workplace:
Dětská klinika, Fakultní nemocnice a Lékařská fakulta Univerzity Palackého, Olomouc
1; Hemato-onkologická klinika, Fakultní nemocnice a Lékařská fakulta Univerzity Palackého, Olomouc
2
Published in:
Čes-slov Pediat 2017; 72 (8): 457-463.
Věnováno panu profesorovi Hrodkovi, zakladateli moderní dětské hematologie v České republice
Overview
Thalassemias represent heterogenic group of inhereted red blood cells disorders. It is caused by imbalance of globin chains in hemoglobin molecule, which leads to ineffective erythropoiesis in a bone marrow and shortening of erythrocyte´s life span. Clinical and laboratory presentation is heterogenic and depends on number of affected genes. Thalassemia carriers are asymptomatic with microcytic erythrocytes and hemoglobin level can be decreased in some cases. Severe forms of thalassemia are associated with severe microcytic hypochromic anemia, an increased hemolysis and with a related complications. Diagnosis of thalassemia consists of analysis of hemoglobin spectrum and detection of the causal mutations by molecular genetic methods.. Carriers of thlassemia allele require no therapy, patients with severe form need a regular transfusion regime. As a curative procedures, hematopoetic stem cell transplantation and gene therapy can be used. Prenatal testing is also available.
Keywords:
α-thalassemia, β-thalassemia, diagnostics, molecular genetic methods
Sources
1. Schechter AN. Hemoglobin research and the origins of molecular medicine. Blood 2008; 112 (10): 3927–3938.
2. Williams TN, Weatherall DJ. World distribution, population genetics, and health burden of the hemoglobinopathies. Review. Cold Spring Harb Perspect Med 2012; 2 (9): a011692.
3. Angastiniotis M, Modell B. Global epidemiology of hemoglobin disorders. Ann N Y Acad Sci 1998; 850: 251–269.
4. Weatherall DJ, Clegg, JB. Inherited haemoglobin disorders: an increasing global health problem. Bull World Health Org 2001; 79: 704–712.
5. Mockenhaupt FP, Ehrhardt S, Gellert S, et al. Alpha(+)-thalassemia protects African children from severe malaria. Blood 2004; 104: 2003–2006.
6. Williams TN, Wambua S, Uyoga S, et al. Both heterozygous and homozygous α + thalassemia protect against severe and fatal Plasmodium falciparum malaria on the coast of Kenya. Blood 2005; 106: 368–371.
7. Pattanapanyasat K, Yongvanitchit K, Tongtawe P, et al. Impairment of Plasmodium falciparum growth in thalassemic red blood cells: further evidence by using biotin labeling and flow cytometry. Blood 1999; 93: 3116–3119.
8. Ayi K, Turrini F, Piga A, et al. Enhanced phagocytosis of ring-parasitized in sickle trait and beta-thalassemia trait. Blood 2004; 104: 3364–3371.
9. Divoký V, Indrák K, Mojzíková R. Hemoglobinopatie: talasémie a strukturní Hb varianty. In: Pospíšilová Š, Dvořáková D, Mayer J (Eds). Molekulární hematologie. Praha: Galén, 2013: 270–283.
10. Mehta RP, Keohane EM. Thalassemias. In: Rodak BF, Fritsma GA, Keohane OA. Hematology: Clinical Principles and Appplications. 4th ed. Missouri: Elsevier, 2012: 408–425.
11. Benz EJ, Schrier SL Landaw SA. Clinical manifestation and diagnosis of the talassemias. www.uptodate.com. Last updated: Dec 17, 2014.
12. Lorey F, Charoenkwan P, Witkowska HE, et al. Hb H hydrops foetalis syndrome: a case report and review of literature. Br J Haematol 2001; 115 (1): 72-78.
13. Carr S, Rubin L, Dixon D et al. Intrauterine therapy for homozygous alpha-thalassemia. Obstet Gynecol 1995; 85 (5 Pt 2): 876–879.
14. Chui DH, Waye JS. Hydrops fetalis caused by alpha-thalassemia: an emerging health care problém. Blood 1998; 91 (7): 2213–2222.
15. Thein SL. Pathophysiology of beta thalassemia – a guide to molecular therapies. Hematology Am Soc Hematol Educ Program 2005: 31–37.
16. Tassiopoulos T, Rombos Y, Konstantopoulos K, et al. Spleen size in beta-thalassaemia heterozygotes. Haematologia (Budap) 1995; 26 (4): 205–209.
17. Karimi M, Bagheri MH, Tahmtan M, et al. Prevalence of hepatosplenomegaly in beta thalassemia minor subjects in Iran. Eur J Radiol 2009; 69 (1): 120–122.
18. Galanello R, Cao A. Relationship between genotype and phenotype: thalassemia intermedia. Ann N Y Acad Sci 1998; 850: 325–333.
19. Taher AT, Musallam KM, Karimi M, et al. Overview on practices in thalassemia intermedia management aiming for lowering complication rates across a region of endemicity: the OPTIMAL CARE study. Blood 2010; 115 (10): 1886–1892.
20. Tanno T, Bhanu NV, Oneal PA, et al. High levels of GDF15 in thalassemia suppress expression of the iron regulatory protein hepcidin. Nat Med 2007 Sep; 13 (9): 1096–1101.
21. Origa R, Galanello R, Ganz T, et al. Liver iron concentrations and urinary hepcidin in beta-thalassemia. Haematologica 2007; 92 (5): 583–588.
22. Oron V, Filon D, Oppenheim A, et al. Severe thalassaemia intermedia caused by interaction of homozygosity for alpha-globin gene triplication with heterozygosity for beta zero-thalassaemia. Br J Haematol 1994; 86 (2): 377–379.
23. Olivieri NF. The beta-thalassemias. Review. N Engl J Med 1999 Jul 8; 341 (2): 99–109. Erratum in: N Engl J Med 1999; 341 (18): 1407.
24. Sirichotiyakul S, Tantipalakorn C, Sanguansermsri T, et al. Erythrocyte osmotic fragility test for screening of alpha-thalassemia-1 and beta-thalassemia trait in pregnancy. Int J Gynaecol Obstet 2004; 86: 347–350.
25. Dragean CA, Duquesne L, Theate I, et al. Extramedullary haemopoiesis and spinal cord compression. Lancet 2011; 377 (9761): 251.
26. Pepe A, Meloni A, Rossi G, et al. Cardiac complications and diabetes in thalassaemia major: a large historical multicentre study. Br J Haematol 2013; 163 (4): 520–527.
27. Fung EB, Harmatz PR, Lee PD, et al. Multi-Centre Study of Iron Overload Research Group. Increased prevalence of iron-overload associated endocrinopathy in thalassaemia versus sickle-cell disease. Br J Haematol 2006; 135 (4): 574–582.
28. Vogiatzi MG, Macklin EA, Trachtenberg FL, et al. Thalassemia Clinical Research Network. Differences in the prevalence of growth, endocrine and vitamin D abnormalities among the various thalassaemia syndromes in North America. Br J Haematol 2009; 146 (5): 546–556.
29. Haines D, Martin M, Carson S, et al. Thalassemia Clinical Research Network. Pain in thalassaemia: the effects of age on pain frequency and severity. Br J Haematol 2013; 160 (5): 680–687.
30. Rachmilewitz EA, Giardina PJ. How I treat thalassemia. Blood 2011; 118 (13): 3479–3488.
31. Goss C, Giardina P, Degtyaryova D, et al. Red blood cell transfusions for thalassemia: results of a survey assessing current practice and proposal of evidence-based guidelines. Transfusion 2014; 54 (7): 1773–1781.
32. Ganz T, Nemeth E. The hepcidin-ferroportin system as a therapeutic target in anemias and iron overload disorders. Hematology Am Soc Hematol Educ Program 2011; 2011: 538–542.
33. Pasricha SR, Frazer DM, Bowden DK, et al. Transfusion suppresses erythropoiesis and increases hepcidin in adult patients with β-thalassemia major: a longitudinal study. Blood 2013; 122 (1): 124–133.
34. Guimarães JS, Cominal JG, Silva-Pinto AC, et al. Altered erythropoiesis and iron metabolism in carriers of thalassemia. Eur J Haematol 2015; 94 (6): 511–518.
35. Jones E, Pasricha SR, Allen A, et al. Hepcidin is suppressed by erythropoiesis in hemoglobin E β-thalassemia and β-thalassemia trait. Blood 2015; 125 (5): 873–880.
36. Thomas ED, Buckner CD, Sanders JE, et al. Marrow transplantation for thalassaemia. Lancet 1982; 2 (8292): 227–229.
37. Angelucci E, Baronciani D. Allogeneic stem cell transplantation for thalassemia major. Haematologica 2008; 93 (12): 1780–1784.
38. Lucarelli G, Gaziev J. Advances in the allogeneic transplantation for thalassemia. Blood Rev 2008; 22 (2): 53–63.
39. Finotti A, Breda L, Lederer CW, et al. Recent trends in the gene therapy of β-thalassemia. J Blood Med 2015; 6: 69–85.
Labels
Neonatology Paediatrics General practitioner for children and adolescentsArticle was published in
Czech-Slovak Pediatrics
2017 Issue 8
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