Thalassemia and sideroblastic anemia are inherited blood disorders characterized by reduced hemoglobin synthesis. Thalassemia results from a genetic mutation affecting either the alpha or beta globin chains, leading to imbalanced globin chain production and anemia. Sideroblastic anemia features iron accumulation in erythroblast mitochondria, causing ineffective red blood cell production. The document defines and compares the genetic causes and clinical manifestations of different types of thalassemia and sideroblastic anemia. Laboratory findings include abnormal hemoglobin levels, red blood cell morphology, and iron studies.

1. THALASSEMIA
SIDEROBLASTIC ANEMIA
Dr SARANYA. R

2. HEMOGLOBINOPATHIES
Thalassemias

3. Definition of hemoglobinopathy
 Clinical diseases that result from a genetically
determined abnormality of the STRUCTURE
or SYNTHESIS of the hemoglobin molecule.
 The abnormality is associated with the globin
chains
 The heme portion of the molecule is normal.

4. GLOBIN ABNORMALITY
QUALITATIVE QUANTITATIVE
•Occurs as a result of
genetic mutations involving
globin protein chain
•Aminoacid deletions or
substitutions
•These mutations cause
structural variations of the
globin chains
•Hb S, Hb C, Hb Metc..
•Occurs as a result of
genetic defects that cause
reduced synthesis of globin
chains
•The globin chains are
structurally normal.
•Collectively known as
THALASSEMIAS

5. What is thalassemia?
 Thalassemia is a group of inherited disorders of hemoglobin
synthesis characterized by a reduced or absent output of one
or more of the globin chains of adult hemoglobin .

6. Type of Hemoglobin
 Hb A
 Hb A2
 Hb F
 Hb H
 Hb Bart’s
α2β2
α2δ2
α2γ2
β4
γ4

7. Demographics: Thalassemia
• Found most frequently
in the Mediterranean,
Africa, Western and
Southeast Asia, India and
Burma
• Distribution parallels that
of Plasmodium
falciparum

8. Types of Thalassemia
  thalassemia: There are four types categorized
according to the severity of their effects on
persons with thalassemia.
 ß thalassemia: There are 3 types categorized
according to severity:
 Thalassemia minor
 Thalassemia intermedia
 Thalassemia major

9. Alpha ( ) thalassemia
 It appears when an individual do not produce
enough alpha chains for hemoglobin.
 It is mainly prevalent in the Africa, the Middle
East , India, and occasionally in Mediterranean
region countries.

10. Beta (ß) thalassemia
It appears when an individual does not produce enough
beta chains for hemoglobin.
It is mainly prevalent in the Mediterranean region
countries , such as Greece, Cyprus, Italy, Palestine and
Lebanon.

11. Classification & Terminology
Alpha Thalassemia
SILENT CARRIER
ALPHA THALASSEMIA TRAIT
HB H DISEASE
HYDROPS FETALIS

12. Symbolism
Alpha Thalassemia
• Greek letter used to designate globin chain:


13. Symbolism
Alpha Thalassemia
/ :Indicates division between genesinherited
from both parents:
/
• Each chromosome 16 carries 2 genes. Therefore the total
complement of  genes in an individual is 4

14. Symbolism
Alpha Thalassemia
- :Indicates a gene deletion:
-/ 

15. Classification & Terminology
Alpha Thalassemia
• Normal
• Silent carrier
• Minor
• Hb H disease
/
- /
-/ -
--/ 
--/-
• Barts hydrops fetalis --/ --

16. Symbolism
Other Thalassemia
• Greek letter used to designate globin chain:


17. Symbolism
Other Thalassemia
0 :Indicates no production of globin chain by
gene:
0

18. Symbolism
Other Thalassemia
+ :Indicates reduced but detectable production
of globin chain by gene:
+

19. Classification & Terminology
Beta Thalassemia
• Normal / 
• Minor
• Intermedia
• Major
/0
/+
0/+
0/0
+/+

20. Genetics of ß thalassemia
 Monogenic disorder: a single gene disorder
 ß thalassemia result from mutations of the ß globin gene
that result in the absence ora decrease in the ß globin
chains

21. Transmission of ß thalassemia
- If a carrier (thalassemia minor) marries a non-
carrier, on average half of their children will be
carriers, but none will develop thalassemia
major.
-However if two carriers marry, in each pregnancy
there is a 25% chance of a non-carrier child, a
50% chance of a carrier child (thalassemia
minor), and a 25% chance of a child with
thalassemia major.

23. ß-Thalassemia Trait /0 /+
 In ß-thalassemia trait (aka ß-thalassemia minor)
defective ß-chain synthesis results in mildly
reduced production of ß+ chains
 The RBCs are microcytic and hypochromic;
often with associated erythrocytosis. The anemia
is usually mild.

24.  High Hemoglobin A2 levels are classic for ß-
thalassemia trait. Hemoglobin F levels are mildly
increased.
 People with ß-thalassemia trait are heterozygous
for either ß o or for ß+.
 If both parents have ß--thalassemia trait their
offspring have a 25% chance of being normal; a
50% chance of having ß-thalassemia trait; and a
25% chance of having ß-thalassemia major.

25.  In thalassemia minor, the severity of disease
expression may only be seen as mild anemia and
a microcytic state.
 It thus may be difficult to distinguish from iron
deficiency.
 Differentiating features include the following:
Thalassemias are more apt to demonstrate
reticulocytosis and basophilic stippling in the
peripheral blood.

26. ß-Thalassemia Intermedia 0/+
 In ß-thalassemia intermedia ß+ chains are made
in amounts intermediate to the major and minor
forms.

27. Thalassemia Major (Cooley's Anemia).
Caused by the unavailability of beta chains in
hemoglobin leading to a very severe and fatal if left
untreated anemia.
It requires regular blood transfusions leading to iron-
overload which is treated with chelation therapy to
prevent death from organ failure.

28.  In ß-thalassemia point mutations or a partial
deletions of chromosome 11 cause defective
synthesis of the ß chain. Over 100 mutations
have been identified.
 Mutations in the promoter affect transcription.
Mutations in the coding regions, splice sites, or
termination codons affect RNA processing and
translation.

29.  Normally a and b globin chains are made in
roughly equal amounts.
 When ß-globin chains are in short supply or
absent, as in ß-thalassemia, a-chains are in
excess. The excess a-chains combine with other
available ß-family globin chains ( d or g) to form
increased amounts of Hgb A2 (a2 d2) and Hgb
F (a2 g 2).
 Hgb Barts ( g4) or tetramers of excess gamma
chains may also form.

30. CLINICAL FEATURES
Clinical manifestations are not seen
until about six months of life when globin
production would normally change from
predominantly g-chain to ß-chain

31.  ß-thalassemia major patients have severe,
transfusion dependent anemia. Nearly all
patients have hepatomegaly and splenomegaly.
 Expansion of the marrow by erythroid
hyperplasia causes enlargement of bones. The
life span of patients with ß-thalassemia major is
short, most dying before adulthood.
 Ironover load, secondary to transfusion
dependency, results in damage to the heart, liver
and endocrine organs.

32. Skull bossing due to expansion of the
diploe ( red bone marrow in the skull)

34. Laboratory findings
 Anemia , usually severe
 PBS shows severe anisocytosis and
poikilocytosis,many microcytes, targets,
elliptocytes, teardrops, and NRBCs.

36.  Serum bilirubin is raised.
 reticulocytosis present
 MCV, MCHC & MCH reduced.

37.  Osmotic fragility :shows increased resistance to
saline hemolysis.
OSMOTIC FRAGILITY IS
DECREASED

38. HEMOGLOBIN ELECTROPHORESIS
 Increased amounts of HbF
 Increased amounts of HbA2
 Complete absence or presence of variable
amounts of HbA

39. Skull X ray - Hair on end appeareance

40. SIDEROBLASTIC ANEMIA

41. SIDEROBLASTS:
These are abnormal nucleated erythroblasts with
granules of IRON accumulated in the mitochondria
surrounding the nucleus.

42. o Sideroblastic anemia are rare
heterogeneous group of refractory anemia
characterized by presence of ring
sideroblast in the bone marrow aspirate.
o A dimorphic peripheral blood picture,
microcytic hypochromic red cells in
hereditary form and macrocytic with
normocytic in acquired form

43. o Tiny iron containing inclusion called
PAPPENHEIMER BODIES ( stain positively
by Prussian blue staining)
o Increased serum iron concentration &
storage iron.
o Ineffective erythropoiesis due to non
viable sideroblasts

45. MORPHOLOGY OF SIDEROBLASTS
TYPE 1 : Fewer than 5 siderotic granule in
the cytoplasm.
TYPE 2 : 5 or more siderotic granule,but
not in a perinuclear distribution
TYPE 3 /RING SIDEROBLASTS : 5 or more
granule in a perinuclear position,
surrounding the nucleus or
encompassing at least one third of
nuclear circumference.

46. CLASSIFICATION
HEREDITARY : ALA Deficiency (Amino
levulinic acid synthase ) : required for
heme synthesis
X-Linked disorder
 ACQUIRED : PRIMARY –idiopathic
SECONDARY

47. HEREDITARY
 Predominently affect males
 Anemia may not manifest until adolescence.
 IRON overload results in
hepatosplenomegaly
impaired growth and development
cardiac arrythmia

48. SECONDARY ACQUIRED
 TOXINS :Lead / zinc poisoning
 DRUGS : INH, ethanol, chloramphenicol
 NUTRITIONAL: Pyredoxine or copper
deficiency
 Indirectly part of myelodysplastic syndrome
 Associated with : leukemia, lymphoma,
polycythemia vera, myelofibrosis

49. • Failure to completely form heme
molecule in the mitochondria leads to
deposition of iron in the mitochondria
that form a ring around the nucleus of
developing RBC

51.  PERIPHERAL SMEAR: RBC shows
dimorphic blood picture with moderate
degree of anisopoikilocytosis.
 Basophilic stippling, pappenheimer body
 RDW INCREASED

58. THANK YOU