The Thalassemias

8,002 views

Published on

What is Thalassemia ,cause ,types ,presentation ,diagnosis ,Differential diagnosis ,Treatment

Published in: Health & Medicine
2 Comments
12 Likes
Statistics
Notes
No Downloads
Views
Total views
8,002
On SlideShare
0
From Embeds
0
Number of Embeds
5
Actions
Shares
0
Downloads
581
Comments
2
Likes
12
Embeds 0
No embeds

No notes for slide

The Thalassemias

  1. 1. The ThalassemiasProf. Dr. Saad S Al AniSenior Pediatric ConsultantHead of Pediatric DepartmentKhorfakkan HospitalSharjah ,UAEsaadsalani@yahoo.com
  2. 2. The Thalassemias Are a group of inherited hematologic disorders caused by defects in the synthesis of one or more of the hemoglobin chains. The Thalassemias Prof. Dr. Saad S Al Ani Khorfakkan Hospital ,Sharjah5 March 2013 ,UAE 2
  3. 3. Cont. •Alpha thalassemia is caused by reduced or absent synthesis of alpha globin chains. • Beta thalassemia is caused by reduced or absent synthesis of beta globin chains.5 March 2013 The Thalassemias Prof. Dr. Saad S Al Ani Khorfakkan Hospital ,Sharjah ,UAE 3
  4. 4. Epidemiology Approximately 5 percent of the worlds population has a globin variant, but only 1.7 percent has alpha or beta thalassemia trait•Thalassemia affects men and women equally and occurs in approximately 4.4 of every10,000 live births Rund D, Rachmilewitz E. Beta- thalassemia. N Engl J Med. 2005;353(11):1135– 1146. The Thalassemias Prof. Dr. Saad S Al Ani Khorfakkan Hospital ,Sharjah 5 March 2013 ,UAE 4
  5. 5. Cont.•Alpha thalassemia occurs most often in persons of African and Southeast Asian descent•Beta thalassemia is most common in persons of Mediterranean, African, and Southeast Asian descent•Thalassemia trait affects 5 to 30 percent of persons in these ethnic groups. Rund D, Rachmilewitz E. Beta- thalassemia. N Engl J Med. 2005;353(11):1135– The Thalassemias Prof. Dr. Saad S Al Ani Khorfakkan Hospital ,Sharjah 5 March 2013 ,UAE 1146. 5
  6. 6. Geographical distribution ofThalassemias The Thalassemias Prof. Dr. Saad S Al Ani Khorfakkan Hospital5 March 2013 ,Sharjah ,UAE 6
  7. 7. Pathophysiology Hemoglobin consists of an iron-containing heme ring and four globin chains: two alpha and two nonalpha.•The composition of the four globin chains determines the hemoglobin type. Structure of human hemoglobin. • The proteins α and β subunits are in red and blue, and the iron-containing heme groups in green. The Thalassemias Prof. Dr. Saad S Al Ani Khorfakkan Hospital ,Sharjah 7 5 March 2013 ,UAE
  8. 8. Normal hemoglobin 5 March 2013 The Thalassemias Prof. Dr. Saad S Al Ani Khorfakkan Hospital ,Sharjah 8 ,UAE
  9. 9. Site of synthesis of globin The Thalassemias Prof. Dr. Saad S Al Ani Khorfakkan Hospital ,Sharjah 95 March 2013 ,UAE
  10. 10. Cont. At birth, Hgb F accounts for approximately 80 percent of hemoglobin and Hgb A accounts for 20 percent.The transition from gamma globin synthesis (Hgb F) to beta globin synthesis (Hgb A)begins before birth.By approximately six months of age, healthy infants will have transitioned to mostly Hgb A, a small amount of Hgb A2, and negligible Hgb F. The Thalassemias Prof. Dr. Saad S Al Ani Khorfakkan Hospital ,Sharjah5 March 2013 ,UAE 10
  11. 11. Cont.•Fetal hemoglobin (Hgb F) has two alpha and two gamma chains (alpha2 gamma2). http://en.wikipedia.org The Thalassemias Prof. Dr. Saad S Al Ani Khorfakkan Hospital ,Sharjah 5 March 2013 ,UAE 11
  12. 12. Cont.•Adult hemoglobin A (Hgb A) has two alpha and two beta chains (alpha2 beta2) http://shamelesslyatheist.wordpress.c om 5 March 2013 The Thalassemias Prof. Dr. Saad S Al Ani Khorfakkan Hospital ,Sharjah ,UAE 12
  13. 13. Cont.•Hemoglobin A2 (HgbA2) has two alpha and two delta chains (alpha2delta2). http://en.wikipedia.org The Thalassemias Prof. Dr. Saad S Al Ani Khorfakkan Hospital ,Sharjah 5 March 2013 ,UAE 13
  14. 14. Alpha Thalassemia  Alpha thalassemia is the result of deficient or absent synthesis of alpha globin chains, leading to excess beta globin chains.•Alpha globin chain production is controlled by two genes on each chromosome 16 •Each of the four alpha globin genes contribute to the synthesis of the alpha globin protein. The Thalassemias Prof. Dr. Saad S Al Ani Khorfakkan Hospital ,Sharjah 14 5 March 2013 ,UAE
  15. 15. Prototypical Forms of AlphaThalassemiaVariant of alphathalassemia Chromosome 16 Signs and symptoms Silent carrier One of four gene Asymptomatic deletionsTrait Two of four gene Asymptomatic deletionsHgb Constant Spring Reduced output of alpha Silent or mildly globin symptomaticIntermedia with significant Three of four gene •Moderate to severeHgb H (Hgb H disease) deletions hemolytic anemia • Modest degree of ineffective erythropoiesis • Splenomegaly • Variable bone changesMajor with significant Four of four gene Causes nonimmuneHgb Barts deletions hydrops fetalis, usually The Thalassemias Prof. Dr. Saad S Al fatal Ani Khorfakkan Hospital ,Sharjah ,UAE 155 March 2013
  16. 16. Chromosome 16gene deletions The Thalassemias Prof. Dr. Saad S Al Ani Khorfakkan Hospital ,Sharjah ,UAE 16 5 March 2013
  17. 17. www.nhlbi.nih.gov The Thalassemias Prof. Dr. Saad S Al Ani Khorfakkan Hospital ,Sharjah ,UAE 175 March 2013
  18. 18. Beta Thalassemia Beta thalassemia is the result of deficient or absent synthesis of beta globin chains, leading to excess alpha chains.•Beta globin synthesis is controlled by one gene on each chromosome 11 •The two gamma globin genes are active during fetal growth and produce Hgb F. •The "adult" gene, beta, takes over after birth. The Thalassemias Prof. Dr. Saad S Al Ani Khorfakkan Hospital ,Sharjah ,UAE 18 5 March 2013
  19. 19. CONT.•Beta thalassemia occurs from any of more than 200 point mutations and (rarely) deletions of the two genes.  Beta globin chain production can range from near normal to completely absent, leading to varying degrees of excess alpha globin to beta globin chain production. 5 March 2013 The Thalassemias Prof. Dr. Saad S Al Ani Khorfakkan Hospital ,Sharjah ,UAE 19
  20. 20. 5 March 2013 The Thalassemias Prof. Dr. Saad S Al Ani Khorfakkan Hospital ,Sharjah ,UAE 20
  21. 21. Prototypical Forms of BetaThalassemiaVariant of Betathalassemia Chromosome 11 Signs and SymptomsTrait One gene defect Asymptomatic Intermedia Two genes defective (mild to Variable degrees of moderate decrease in beta severity of symptoms globin synthesis) of thalassemia major Major Two genes defective (severe •Abdominal swelling decrease in beta globin • Growth retardation synthesis) •Irritability • Jaundice, pallor •Skeletal abnormalities • Splenomegaly • Requires lifelong blood transfusions The Thalassemias Prof. Dr. Saad S Al Ani Khorfakkan Hospital ,Sharjah ,UAE 21 5 March 2013
  22. 22. Chromosome 11 gene defect The Thalassemias Prof. Dr. Saad S Al Ani Khorfakkan Hospital ,Sharjah5 March 2013 ,UAE 22
  23. 23. Severity of β-Thalassemia5 March 2013 The Thalassemias Prof. Dr. Saad S Al Ani Khorfakkan Hospital ,Sharjah ,UAE 23
  24. 24. Beta Thalassemia –bone changes surgerypicts.blogspot.com The Thalassemias Prof. Dr. Saad S Al Ani Khorfakkan Hospital ,Sharjah5 March 2013 ,UAE 24
  25. 25. Anteroposterior radiograph of the lumbar spine. Osteopenia is present; striated appearance of the vertebral bodies resultingfrom preservation and thickening of the vertical trabeculae. Clips from a previous cholecystectomy are present.5 March 2013 The Thalassemias Prof. Dr. Saad S Al Ani Khorfakkan Hospital ,Sharjah ,UAE 25
  26. 26. Lateral skull radiograph. Widening of the calvarium is present; -The outer table overlying the frontal region is obliterated - New bone formation can be seen in the diploë, producing a "hair-on-end“ appearance.5 March 2013 The Thalassemias Prof. Dr. Saad S Al Ani Khorfakkan Hospital ,Sharjah ,UAE 26
  27. 27. Anteroposterior of the hands.. A generalized loss of bone density is observed. -The cortex is thinned -The trabeculae are coarsened - Outline localized lucency.. Widening of the medullary cavity has resulted in squaring of the metacarpals - The enlarged nutrient foramina in the middle phalanges. The Thalassemias Prof. Dr. Saad S Al Ani Khorfakkan Hospital ,Sharjah ,UAE 275 March 2013
  28. 28. Anteroposterior radiograph of the forearm. A fracture is noted in the distal radius. Evidence of medullary expansion and cortical thinning is observed.5 March 2013 The Thalassemias Prof. Dr. Saad S Al Ani Khorfakkan Hospital ,Sharjah ,UAE 28
  29. 29. Radiograph of the ribs.Erosions of the inferior cortical margins of the third, fourth, and fifth ribs are noted.5 March 2013 The Thalassemias Prof. Dr. Saad S Al Ani Khorfakkan Hospital ,Sharjah ,UAE 29
  30. 30. Other β-ThalassemiaSyndromes The β-thalassemia syndromes are broken into six groups: 1. β-thalassemia 2. δβ- Thalassemias 3. γ- Thalassemias 4. δ-thalassemias 5. ϵγδβ- Thalassemias 6. the HPFH syndrome. The Thalassemias Prof. Dr. Saad S Al Ani Khorfakkan Hospital ,Sharjah ,UAE 305 March 2013
  31. 31. Pathogenesis of Beta Thalassemia medicinembbs.blogspot.co The Thalassemias m Prof. Dr. Saad S Al Ani Khorfakkan Hospital ,Sharjah ,UAE 315 March 2013
  32. 32. CONT.  The one gene defect, beta thalassemia trait (minor) is asymptomatic and results in microcytosis and mild anemia. •If the synthesis from both genes is severely reduced or absent, the person has beta thalassemia major, also known as Cooley anemia.5 March 2013 The Thalassemias Prof. Dr. Saad S Al Ani Khorfakkan Hospital ,Sharjah ,UAE 32
  33. 33. CONT .•If the synthesis of beta chains is less severely reduced , the person has beta thalassemia intermedia. Persons with beta thalassemia major are almost never symptomatic at birth because of the presence of Hgb F, but symptoms begin to develop by six months of age.5 March 2013 The Thalassemias Prof. Dr. Saad S Al Ani Khorfakkan Hospital ,Sharjah ,UAE 33
  34. 34. Diagnosis Most persons with thalassemia trait are found incidentally when their complete blood count shows a mild microcytic anemia•Microcytic anemia can be caused by: 1. Iron deficiency 2.Thalassemia 3. Lead poisoning 4.Sideroblastic anemia 5.Anemia of chronic disease.5 March 2013 The Thalassemias Prof. Dr. Saad S Al Ani Khorfakkan Hospital ,Sharjah ,UAE 34
  35. 35. CONT.  To exclude some of these etiologies , the followings can help: - Mean corpuscular volume (MCV) - Red blood cell distribution width (RDW) - Patients history5 March 2013 The Thalassemias Prof. Dr. Saad S Al Ani Khorfakkan Hospital ,Sharjah ,UAE 35
  36. 36. Hematologic Indices of IronDeficiency and Alpha and BetaThalassemiaTest Iron deficiency Beta thalassemia Alpha thalassemiaMCV (abnormal if Low Low Low• < 70 fl in children six months to six years ofage• < 76 fl in childrenseven to 12 years of age)Red blood cell High Normal; Normaldistribution width(RDW) occasionally highFerritin Low Normal NormalMentzer index for > 13 < 13 < 13children (MCV/red bloodcell count)Hgb electrophoresis Normal (may •↑ Hgb A2 Newborns: may have↓ HbA2) • ↓ Hgb A have Hgb H or Hgb Barts •Probably↑ Hgb F5 March 2013 The Thalassemias Prof. Dr. Saad S Al Ani Khorfakkan Hospital ,Sharjah ,UAE 36
  37. 37. Use of RDW Values in the Diagnosis of Thalassemia Microcytic Anemia Children 6 months -6 years of age: MCV <70fl Children 7 to 12 years of age: MCV <76fl ↓ RDW ↓ ↓ Normal Elevated (>15) ↓ ↓ Favors Ferritin level Thalassemia ↓ ↓ Normal(>100ng/m Low(<10ng/mL) L) ↓ ↓ The Thalassemias Prof. Dr. Saad S Al Ani Khorfakkan Hospital ,Sharjah ,UAE Favors Favors Iron Deficiency 375 March 2013
  38. 38. Supplemental tests  Include: - Serum ferritin - The peripheral smear - Hemoglobin electrophoresis - Serum lead level - Rarely bone marrow aspirate 5 March 2013 The Thalassemias Prof. Dr. Saad S Al Ani Khorfakkan Hospital ,Sharjah ,UAE 38
  39. 39. The peripheral smear of Thalassemia major www.wardelab.com5 March 2013 The Thalassemias Prof. Dr. Saad S Al Ani Khorfakkan Hospital ,Sharjah ,UAE 39
  40. 40. Cont.  The hemoglobin electrophoresis with beta thalassemia trait usually has: - Reduced or absent Hgb A - Elevated levels of Hgb A2 - Increased Hgb F •A normal concentration of HbA2 does not rule out beta thalassemia trait, especially if there was coexistent iron deficiency5 March 2013 The Thalassemias Prof. Dr. Saad S Al Ani Khorfakkan Hospital ,Sharjah ,UAE 40
  41. 41. The hemoglobin electrophoresis5 March 2013 The Thalassemias Prof. Dr. Saad S Al Ani Khorfakkan Hospital ,Sharjah ,UAE 41
  42. 42. Time of complications ofThalassemia www.nyas.org 5 March 2013 The Thalassemias Prof. Dr. Saad S Al Ani Khorfakkan Hospital ,Sharjah ,UAE 42
  43. 43. Treatment  Blood Transfusions  Iron Chelation Therapy  Splenectomy  Bone Marrow Transplant5 March 2013 The Thalassemias Prof. Dr. Saad S Al Ani Khorfakkan Hospital ,Sharjah ,UAE 43
  44. 44. Cont. Beginning transfusion and chelation therapy are difficult challenges for parents to face early in their childs life.• Blood products that are leukoreduced andphenotypically matched for the Rh andKell antigens are required for transfusion 5 March 2013 The Thalassemias Prof. Dr. Saad S Al Ani Khorfakkan Hospital ,Sharjah ,UAE 44
  45. 45. Cont. If a bone marrow transplant is a possibility, the blood for transfusion should be negative for cytomegalovirus•Hematopoietic stem cell transplantation has cured >1,000 patients who have β- thalassemia major.5 March 2013 The Thalassemias Prof. Dr. Saad S Al Ani Khorfakkan Hospital ,Sharjah ,UAE 45
  46. 46. Cont.  Most success has been in children 1. younger than 15 yr of age 2. without excessive iron stores and hepatomegaly 3. who undergo sibling HLA-matched allogeneic transplantation. •All children who have an HLA-matched sibling should be offered the option of bone marrow transplantation The Thalassemias Prof. Dr. Saad S Al Ani Khorfakkan Hospital ,Sharjah5 March 2013 ,UAE 46
  47. 47. Prevention Blood tests and family genetic studies can show whether an individual has thalassemia or is a carrier.•A genetic counselor can detail the family background, discuss risks, and give you information on available testing.5 March 2013 The Thalassemias Prof. Dr. Saad S Al Ani Khorfakkan Hospital ,Sharjah ,UAE 47
  48. 48. Summary1. Imbalances of globin chains cause: - Hemolysis - Impair erythropoiesis2.Silent carriers of alpha thalassemia and persons with alpha or beta thalassemia trait are asymptomatic and require no treatment.3.Alpha thalassemia intermedia, or hemoglobin H disease, causes hemolytic anemia. http://www.aafp.org The Thalassemias Prof. Dr. Saad S Al Ani Khorfakkan Hospital ,Sharjah ,UAE 485 March 2013
  49. 49. Cont.4.Alpha thalassemia major with hemoglobin Barts usually results in fatal hydrops fetalis5.Beta thalassemia major causes: - Hemolytic anemia - Poor growth - Skeletal abnormalities during infancy6.Affected children will require regular lifelong blood transfusions.5 March 2013 The Thalassemias Prof. Dr. Saad S Al Ani Khorfakkan Hospital ,Sharjah ,UAE 49
  50. 50. Cont. 7.Beta thalassemia intermedia is less severe than beta thalassemia major and may require episodic blood transfusions 8.Transfusion-dependent patients will develop iron overload and require chelation therapy to remove the excess iron http://www.aafp.org5 March 2013 The Thalassemias Prof. Dr. Saad S Al Ani Khorfakkan Hospital ,Sharjah ,UAE 50
  51. 51. Cont.10.Bone marrow transplants can be curative for some children with beta thalassemia major11.Persons with the thalassemia trait have a normal life expectancy. 12.Persons with beta thalassemia major often die from cardiac complications of iron overload by 30 years of age. http://www.aafp.org 5 March 2013 The Thalassemias Prof. Dr. Saad S Al Ani Khorfakkan Hospital ,Sharjah ,UAE 51
  52. 52. The Thalassemias Prof. Dr. Saad S Al Ani Khorfakkan Hospital ,Sharjah ,UAE 525 March 2013
  53. 53. When this picture will disappear? http://soulverses.org/5 March 2013 The Thalassemias Prof. Dr. Saad S Al Ani Khorfakkan Hospital ,Sharjah ,UAE 53
  54. 54. 54

×