Pediatric Thalassemia Differential Diagnoses

  • Author: Hassan M Yaish, MD; Chief Editor: Max J Coppes, MD, PhD, MBA   more...
 
Updated: Apr 30, 2010
 
 
 
Contributor Information and Disclosures
Author

Hassan M Yaish, MD  Professor of Pediatrics, University of Utah School of Medicine; Director of Hematology Services, Medical Director, Mountain States Hemophilia and Thrombophilia Treatment Center; Pediatric Hematologist/Oncologist, Department of Pediatrics, Primary Children's Medical Center

Hassan M Yaish, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Michigan State Medical Society, and New York Academy of Sciences

Disclosure: Nothing to disclose.

Specialty Editor Board

J Martin Johnston, MD  Associate Professor of Pediatrics, Mercer University School of Medicine; Director of Hematology/Oncology, The Children's Hospital at Memorial University Medical Center; Consulting Oncologist/Hematologist, St Damien's Pediatric Hospital

J Martin Johnston, MD is a member of the following medical societies: American Academy of Pediatrics and American Society of Pediatric Hematology/Oncology

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

James L Harper, MD  Associate Professor, Department of Pediatrics, Division of Hematology/Oncology and Bone Marrow Transplantation, Associate Chairman for Education, Department of Pediatrics, University of Nebraska Medical Center; Assistant Clinical Professor, Department of Pediatrics, Creighton University School of Medicine; Director, Continuing Medical Education, Children's Memorial Hospital; Pediatric Director, Nebraska Regional Hemophilia Treatment Center

James L Harper, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for Cancer Research, American Federation for Clinical Research, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Council on Medical Student Education in Pediatrics, and Hemophilia and Thrombosis Research Society

Disclosure: Nothing to disclose.

Helen SL Chan, MBBS, FRCP(C), FAAP  Senior Scientist, Research Institute; Professor, Division of Hematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Canada

Helen SL Chan, MBBS, FRCP(C), FAAP is a member of the following medical societies: American Academy of Pediatrics, American Association for Cancer Research, American Society of Hematology, and Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Chief Editor

Max J Coppes, MD, PhD, MBA  Senior Vice President, Center for Cancer and Blood Disorders, Children's National Medical Center; Professor of Medicine, Oncology, and Pediatrics, Georgetown University School of Medicine; Clinical Professor of Pediatrics, George Washington University School of Medicine and Health Sciences

Max J Coppes, MD, PhD, MBA is a member of the following medical societies: American Association for Cancer Research, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research

Disclosure: Nothing to disclose.

References
  1. Joly P, Lacan P, Garcia C, Couprie N, Francina A. Identification and molecular characterization of four new large deletions in the beta-globin gene cluster. Blood Cells Mol Dis. Mar 6 2009;[Medline].

  2. Nemeth E. Targeting the hepcidine-ferroportin axis in the diagnosis and treatment of anemias. Adv Hematol. 2010;[Medline].

  3. Deborah Chirnomas S, Geukes-Foppen M, Barry K, et al. Practical implications of liver and heart iron load assessment by T2*-MRI in children and adults with transfusion-dependent anemias. Am J Hematol. Oct 2008;83(10):781-3. [Medline].

  4. Hankins JS, McCarville MB, Loeffler RB, et al. R2* magnetic resonance imaging of the liver in patients with iron overload. Blood. Mar 4 2009;[Medline].

  5. Lucarelli G, Galimberti M, Polchi P, et al. Marrow transplantation in patients with thalassemia responsive to iron chelation therapy. N Engl J Med. Sep 16 1993;329(12):840-4. [Medline].

  6. Gharagozloo M, Bagherpour B, Tahanian M, et al. Premature senescence of T lymphocytes from patients with beta-thalassemia major. Immunol Lett. Jan 29 2009;122(1):84-8. [Medline].

  7. Ghaffari J, Vahidshahi K, Kosaryan M, Parvinnejad N, Mahdavi M, Karami H. Nitroblue tetrazolium test in patients with beta-thalassemia major. Saudi Med J. Nov 2008;29(11):1601-5. [Medline].

  8. Davison SM, Kelly DA. Management strategies for hepatitis C virus infection in children. Paediatr Drugs. 2008;10(6):357-65. [Medline].

  9. Finkenstedt A, Bianchi P, Theurl I, et al. Regulation of iron metabolism through GDF15 and hepcidin in pyruvate kinase deficiency. Br J Haematol. Mar 2009;144(5):789-93. [Medline].

  10. Cappellini MD. Long-term efficacy and safety of deferasirox. Blood Rev. Dec 2008;22 Suppl 2:S35-41. [Medline].

  11. Agarwal MB. Deferasirox: oral, once daily iron chelator--an expert opinion. Indian J Pediatr. Feb 2010;77(2):185-91. [Medline].

  12. Bauters T, Mondelaers V, Robays H, Hunninck K, de Moerloose B. Gastric ulcer in a child treated with deferasirox. Pharm World Sci. Apr 2010;32(2):112-3. [Medline].

  13. Marktel S, Napolitano S, Zino E, et al. Platelet transfusion refractoriness in highly immunized beta thalassemia children undergoing stem cell transplantation. Pediatr Transplant. Jan 7 2010;[Medline].

  14. Noe A, Cappelli B, Biffi A, et al. High incidence of severe cyclosporine neurotoxicity in children affected by haemoglobinopaties undergoing myeloablative haematopoietic stem cell transplantation: early diagnosis and prompt intervention ameliorates neurological outcome. Ital J Pediatr. Feb 6 2010;36(1):14. [Medline].

  15. Italia KY, Jijina FF, Merchant R, et al. Effect of hydroxyurea on the transfusion requirements in patients with severe HbE-beta-thalassaemia: a genotypic and phenotypic study. J Clin Pathol. Feb 2010;63(2):147-50. [Medline].

  16. Saewong T, Ounjaijean S, Mundee Y, et al. Effects of Green Tea on Iron Accumulation and Oxidative Stress in Livers of Iron-Challenged Thalassemic Mice. Med Chem. Mar 11 2010;[Medline].

  17. Koren A, Levin C, Dgany O, et al. Response to hydroxyurea therapy in beta-thalassemia. Am J Hematol. May 2008;83(5):366-70. [Medline].

  18. Karimi M, Borzouee M, Mehrabani A, Cohan N. Echocardiographic finding in beta-thalassemia intermedia and major: absence of pulmonary hypertension following hydroxyurea treatment in beta-thalassemia intermedia. Eur J Haematol. Mar 2009;82(3):213-8. [Medline].

  19. Geffner ME, Karlsson H. Use of recombinant human growth hormone in children with thalassemia. Horm Res. Jan 2009;71 Suppl 1:46-50. [Medline].

  20. [Guideline] Langlois S, Ford JC, Chitayat D, et al. Carrier screening for thalassemia and hemoglobinopathies in Canada. J Obstet Gynaecol Can. Oct 2008;30(10):950-71. [Medline].

  21. Cowan RS. Moving up the slippery slope: mandated genetic screening on Cyprus. Am J Med Genet C Semin Med Genet. Feb 15 2009;151C(1):95-103. [Medline].

  22. Srivorakun H, Fucharoen G, Sae-Ung N, Sanchaisuriya K, Ratanasiri T, Fucharoen S. Analysis of fetal blood using capillary electrophoresis system: a simple method for prenatal diagnosis of severe thalassemia diseases. Eur J Haematol. Feb 17 2009;[Medline].

  23. Winichagoon P, Svasti S, Munkongdee T, et al. Rapid diagnosis of thalassemias and other hemoglobinopathies by capillary electrophoresis system. Transl Res. Oct 2008;152(4):178-184. [Medline].

  24. Yi P, Chen Z, Yu L, et al. Development of a PCR/LDR/capillary electrophoresis assay with potential for the detection of a beta-thalassemia fetal mutation in maternal plasma. J Matern Fetal Neonatal Med. Feb 1 2010;[Medline].

  25. Barnett CF, Hsue PY, Machado RF. Pulmonary hypertension: an increasingly recognized complication of hereditary hemolytic anemias and HIV infection. JAMA. Jan 23 2008;299(3):324-31. [Medline].

  26. Morris CR, Gladwin MT, Kato GJ. Nitric oxide and arginine dysregulation: a novel pathway to pulmonary hypertension in hemolytic disorders. Curr Mol Med. Nov 2008;8(7):620-32. [Medline].

  27. El-Beshlawy A, Youssry I, El-Saidi S, et al. Pulmonary hypertension in beta-thalassemia major and the role of L-carnitine therapy. Pediatr Hematol Oncol. Dec 2008;25(8):734-43. [Medline].

  28. Metarugcheep P, Chanyawattiwongs S, Srisubat K, Pootrakul P. Clinical silent cerebral infarct (SCI) in patients with thalassemia diseases assessed by magnetic resonance imaging (MRI). J Med Assoc Thai. Jun 2008;91(6):889-94. [Medline].

  29. Parker TM, Ward LM, Johnston DL, Ventureya E, Klaassen RJ. A case of Moyamoya syndrome and hemoglobin E/beta-thalassemia. Pediatr Blood Cancer. Mar 2009;52(3):422-4. [Medline].

  30. Goldschmidt N, Spectre G, Brill A, et al. Increased platelet adhesion under flow conditions is induced by both thalassemic platelets and red blood cells. Thromb Haemost. Nov 2008;100(5):864-70. [Medline].

  31. Singer ST, Ataga KI. Hypercoagulability in sickle cell disease and beta-thalassemia. Curr Mol Med. Nov 2008;8(7):639-45. [Medline].

  32. Fung EB, Harmatz PR, Lee PD, et al. Increased prevalence of iron-overload associated endocrinopathy in thalassaemia versus sickle-cell disease. Br J Haematol. Nov 2006;135(4):574-82. [Medline].

  33. Delvecchio M, Cavallo L. Growth and endocrine function in thalassemia major in childhood and adolescence. J Endocrinol Invest. Jan 2010;33(1):61-8. [Medline].

  34. Poggi M, Pascucci C, Monti S, et al. Prevalence of Growth hormone (GH) Deficiency in Adult polytransfused betaThalassaemia patients (TM) and correlation with Transfusional and Chelation Parameters. J Endocrinol Invest. Feb 15 2010;[Medline].

  35. De Sanctis V, Borsari G, Brachi S, Govoni M, Carandina G. Spermatogenesis in young adult patients with beta-thalassaemia major long-term treated with desferrioxamine. Georgian Med News. Mar 2008;74-7. [Medline].

  36. Karabulut A, Balci Y, Demirlenk S, Semiz S. Gonadal dysfunction and pelvic sonographic findings in females with thalassaemia major. Gynecol Endocrinol. Apr 2010;26(4):307-10. [Medline].

  37. Atichartakarn V, Angchaisuksiri P, Aryurachai K, et al. In vivo platelet activation and hyperaggregation in hemoglobin E/beta-thalassemia: a consequence of splenectomy. Int J Hematol. Apr 2003;77(3):299-303. [Medline].

  38. Aypar E, Alehan D, Hazirolan T, Gumruk F. The efficacy of tissue Doppler imaging in predicting myocardial iron load in patients with beta-thalassemia major: correlation with T2* cardiovascular magnetic resonance. Int J Cardiovasc Imaging. Apr 2010;26(4):413-21. [Medline].

  39. Beutler E, Hoffbrand AV, Cook JD. Iron deficiency and overload. Hematology (Am Soc Hematol Educ Program). 2003;40-61. [Medline].

  40. Borgna-Pignatti C, Vergine G, Lombardo T, et al. Hepatocellular carcinoma in the thalassaemia syndromes. Br J Haematol. Jan 2004;124(1):114-7. [Medline].

  41. Cao A, Rosatelli C, Galanello R, et al. The prevention of thalassemia in Sardinia. Clin Genet. Nov 1989;36(5):277-85. [Medline].

  42. Cappellini MD, Cohen A, Piga A, et al. A phase 3 study of deferasirox (ICL670), a once-daily oral iron chelator, in patients with beta-thalassemia. Blood. May 1 2006;107(9):3455-62. [Medline].

  43. Cario H, Janka-Schaub G, Janssen G, et al. Recent developments in iron chelation therapy. Klin Padiatr. May-Jun 2007;219(3):158-65. [Medline].

  44. Centis F, Tabellini L, Lucarelli G, et al. The importance of erythroid expansion in determining the extent of apoptosis in erythroid precursors in patients with beta-thalassemia major. Blood. Nov 15 2000;96(10):3624-9. [Medline].

  45. Chakravarti A, Verma V, Kumaria R, Dubey AP. Anti HCV seropositivity among multi transfused patients with beta-thalassemia. J indian Med Assoc. 2005;103(2):64-66. [Medline].

  46. Christoforidis A, Haritandi A, Tsatra I, et al. Four-year evaluation of myocardial and liver iron assessed prospectively with serial MRI scans in young patients with beta-thalassaemia major: comparison between different chelation regimens. Eur J Haematol. Jan 2007;78(1):52-7. [Medline].

  47. Cunningham MJ, Macklin EA, Neufeld EJ, et al. Complications of beta-thalassemia major in North America. Blood. Jul 1 2004;104(1):34-9. [Medline].

  48. De Virgiliis S, Cossu P, Toccafondi C, et al. Effect of subcutaneous desferrioxamine on iron balance in young thalassemia major patients. Am J Pediatr Hematol Oncol. Spring 1983;5(1):73-7. [Medline].

  49. dos Santos CO, Costa FF. AHSP and beta-thalassemia: a possible genetic modifier. Hematology. 2005;10(2):57-61. [Medline].

  50. Economou M, Printza N, Teli A, et al. Renal dysfunction in patients with beta-thalassemia major receiving iron chelation therapy either with deferoxamine and deferiprone or with deferasirox. Acta Haematol. 2010;123(3):148-52. [Medline].

  51. Fucharoen S, Ketvichit P, Pootrakul P, et al. Clinical manifestation of beta-thalassemia/hemoglobin E disease. J Pediatr Hematol Oncol. Nov-Dec 2000;22(6):552-7. [Medline].

  52. Gardenghi S, Marongiu MF, Ramos P, et al. Ineffective erythropoiesis in beta-thalassemia is characterized by increased iron absorption mediated by down-regulation of hepcidin and up-regulation of ferroportin. Blood. Jun 1 2007;109(11):5027-35. [Medline].

  53. Gilman JG, Huisman TH, Abels J. Dutch beta 0-thalassaemia: a 10 kilobase DNA deletion associated with significant gamma-chain production. Br J Haematol. Feb 1984;56(2):339-48. [Medline].

  54. Haldane JBS. The rate of mutation of human genes. In: Proceedings of the VIII International Congress on Genetics and Heredity. 1949;267.

  55. Hershko C, Weatherall DJ. Iron-chelating therapy. Crit Rev Clin Lab Sci. 1988;26(4):303-45. [Medline].

  56. Kazazian HH Jr. The thalassemia syndromes: molecular basis and prenatal diagnosis in 1990. Semin Hematol. Jul 1990;27(3):209-28. [Medline].

  57. Kazazian HH Jr, Boehm CD. Molecular basis and prenatal diagnosis of beta-thalassemia. Blood. Oct 1988;72(4):1107-16. [Medline].

  58. Kontoghiorghes GJ. Deferasirox: uncertain future following renal failure fatalities, agranulocytosis and other toxicities. Expert Opin Drug Saf. May 2007;6(3):235-9. [Medline].

  59. Lilleyman JS, Hann IM, Blanchette V. The thalassemia. Pediatr Hematol. 2000;307-327.

  60. Lorey F. Asian immigration and public health in California: thalassemia in newborns in California. J Pediatr Hematol Oncol. Nov-Dec 2000;22(6):564-6. [Medline].

  61. Mentzer WC Jr. Differentiation of iron deficiency from thalassaemia trait. Lancet. Apr 21 1973;1(7808):882. [Medline].

  62. Mohkam M, Shamsian BS, Gharib A, Nariman S, Arzanian MT. Early markers of renal dysfunction in patients with beta-thalassemia major. Pediatr Nephrol. Jun 2008;23(6):971-6. [Medline].

  63. Nagel RL, Roth EF Jr. Malaria and RBC genetic defects. Blood. Sep 1989;74(4):1213-21. [Medline].

  64. Nathan DG, Gunn RB. Thalassemia: the consequences of unbalanced hemoglobin synthesis. Am J Med. Nov 1966;41(5):815-30. [Medline].

  65. Nathan DG, Oski FA. The thalassemia. In: Hematology of Infancy and Childhood. Vol 1. Philadelphia, Pa: WB Saunders Co;1998:783-879, 811-886.

  66. Nick H, Acklin P, Lattmann R, et al. Development of tridentate iron chelators: from desferrithiocin to ICL670. Curr Med Chem. Jun 2003;10(12):1065-76. [Medline].

  67. Olivieri NF, Brittenham GM, Matsui D, et al. Iron-chelation therapy with oral deferipronein patients with thalassemia major. N Engl J Med. Apr 6 1995;332(14):918-22. [Medline].

  68. Origa R, Galanello R, Ganz T, et al. Liver iron concentrations and urinary hepcidin in beta-thalassemia. Haematologica. May 2007;92(5):583-8. [Medline].

  69. Orkin SH, Kazazian HH Jr. The mutation and polymorphism of the human beta-globin gene and its surrounding DNA. Annu Rev Genet. 1984;18:131-71. [Medline].

  70. Pakbaz Z, Fischer R, Fung E, et al. Serum ferritin underestimates liver iron concentration in transfusion independent thalassemia patients as compared to regularly transfused thalassemia and sickle cell patients. Pediatr Blood Cancer. Sep 2007;49(3):329-32. [Medline].

  71. Pakpaz FR, Fung E, Harmatz P. Serum ferritin underestimates the liver iron concentration. Pediatric Blood and Cancer. 2004;42:497.

  72. Pan LL, Eng HL, Kuo CY, et al. Usefulness of brilliant cresyl blue staining as an auxiliary method of screening for alpha-thalassemia. J Lab Clin Med. Feb 2005;145(2):94-7. [Medline].

  73. Peters TJ, Raja KB, Simpson RJ, Snape S. Mechanisms and regulation of intestinal iron absorption. Ann N Y Acad Sci. 1988;526:141-7. [Medline].

  74. Piomelli S, Danoff SJ, Becker MH, et al. Prevention of bone malformations and cardiomegaly in Cooley's anemia by early hypertransfusion regimen. Ann N Y Acad Sci. Nov 20 1969;165(1):427-36. [Medline].

  75. Pippard MJ, Callender ST, Weatherall DJ. Intensive iron-chelation therapy with desferrioxamine in iron-loading anaemias. Clin Sci Mol Med. Jan 1978;54(1):99-106. [Medline].

  76. Premawardhena A, Fisher CA, Fathiu F, et al. Genetic determinants of jaundice and gallstones in haemoglobin E beta thalassaemia. Lancet. Jun 16 2001;357(9272):1945-6. [Medline].

  77. Reich S, Buhrer C, Henze G, et al. Oral isobutyramide reduces transfusion requirements in some patients with homozygous beta-thalassemia. Blood. Nov 15 2000;96(10):3357-63. [Medline].

  78. Ross J, Pizarro A. Human beta and delta globin messenger RNAs turn over at different rates. J Mol Biol. Jul 5 1983;167(3):607-17. [Medline].

  79. Roy CN, Enns CA. Iron homeostasis: new tales from the crypt. Blood. Dec 15 2000;96(13):4020-7. [Medline].

  80. Singer ST, Wu V, Mignacca R, et al. Alloimmunization and erythrocyte autoimmunization in transfusion- dependent thalassemia patients of predominantly asian descent. Blood. Nov 15 2000;96(10):3369-73. [Medline].

  81. Tanner MA, Galanello R, Dessi C, et al. A randomized, placebo-controlled, double-blind trial of the effect of combined therapy with deferoxamine and deferiprone on myocardial iron in thalassemia major using cardiovascular magnetic resonance. Circulation. Apr 10 2007;115(14):1876-84. [Medline].

  82. Thein SL. Dominant beta thalassaemia: molecular basis and pathophysiology. Br J Haematol. 1992;80(3):273-7. [Medline].

  83. Vichinsky EP. Reports of proceedings: 1999 international conference on E-Beta thalassemia. J Pediatr Hematol Oncol. 2000;22:6:550.

  84. Voskaridou E, Terpos E, Spina G, et al. Pamidronate is an effective treatment for osteoporosis in patients with beta-thalassaemia. Br J Haematol. Nov 2003;123(4):730-7. [Medline].

  85. Weatherall DJ. Thalassemia. In: Stamatoyannopoulos G et al, eds. The Molecular Basis of Blood Diseases. 1944:157-206.

  86. Weatherall DJ. Thalassemia. In: The Thalassemia Syndromes. 1981.

  87. Wintrobe MM, Mathews E. Familial hematopoietic disorder in Italian adolescents and adults resembling Mediterranean disease (thalassemia). JAMA. 1940;114:1530-4.

Previous
Next
 
Alpha chain genes in duplication on chromosome 16 pairing with non-alpha chains to produce various normal hemoglobins.
Alpha and beta globin genes (chromosomes 16 and 11, respectively).
Various mutations in the beta gene that result in beta thalassemia.
Supra vital stain in hemoglobin H disease that reveals Heinz bodies (golf ball appearance).
Peripheral blood film in Cooley anemia.
Peripheral blood film in thalassemia minor.
Peripheral blood film in hemoglobin H disease in a newborn.
Peripheral blood in iron deficiency anemia.
The classic "hair on end" appearance on plain skull radiographs of a patient with Cooley anemia.
Excessive iron in a bone marrow preparation.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.