detail about thalassemia

1. THALASSEMIA

2. • Heterogenous group of autosomal recessive Inherited disorders of
α- or β- globin chain biosynthesis which diminishes production of
hemoglobin tetramers, causing hypochromia and microcytosis.
• Unbalanced accumulation of α and β sub-units occurs because
synthesis of unaffected globin proceeds at normal rate
• 2 types :
• α thalassemia
• β thalassemia
Thalassemia

3. HEMOGLOBIN:
• Types of globin subunit:
• α sub-unit
• β sub-unit
• γ sub-unit
• δ sub-unit
• Types of hemoglobin:
• HbF : 2α, 2γ
• HbA : 2α, 2β
• Hb𝐴2: 2α, 2δ

4. Β-THALASSEMIA
• β0 -Thalassemia: absence of production of the β-globin.
• β+ -Thalassemia indicates a mutation that makes decreased amounts of normal β-
globin.
Classification Genotype Severity
Minor/ trait β/β0, β/β+ silent
intermedia β+/β+, β+/β0 Moderate
severe β0/β0 severe

5. Mutation on chromosome
11 ( the β like globin genes
are clustered on
chromosome 11)
Decreased β-chain
production but synthesis of
α-chain is unaffected
profound anemia
stimulates erythropoietin
release and
compensatory erythroid
hyperplasia occurs.
Accumulation of α-chain
Formation of
inclusion
bodies
Affects any steps in globin gene
expression i.e. transcription,
processing of the mRNA precursor,
translation, and posttranslational
metabolism of the β-globin
polypeptide chain.
Hemolytic anemia
erythroid hyperplasia
becomes excessive
Pathophysiology:
produce mass of
extra-medullary
erythropoietic tissue
in liver and spleen
damage RBC membrane and
kill developing RBC in
marrow

6. CLINICAL FEATURES:
Thalassemia major: cooley’s anemia, homozygous anemia
• Severe anemia beginning in late infancy
• Jaundice and dark urine
• Massive hepatosplenomegaly
• Growth retardation and failure to thrive
• Chipmunk facies: maxillary marrow hyperplasia, flat nasal bridge and frontal bossing
• Thinning and pathological fractures of long bones dur to cortical involvement of
erythroid
• Crew cut appearance on x-ray of skull: due to expansion of bone marrow space
Dueto
hemolysis
• Thalassemia intermediate:
• Anemia of varying severity
• Thalassemia minor
• Asymptomatic carrier state or mild anemia

7. DIAGNOSIS:
• By clinical signs and symptoms
• By serum electrophoresis
• Elevated HbF and Hb𝐴2
• By peripheral blood smear:
• Reveals microcytic, hypochromic anemia and target cells
• By blood test:
• Low MCV (microcytosis)
• Low MCH (hypochromia)
• Low Hb

8. TREATMENT:
• Genetic counselling and patient education
• β-thalassemia minor: treatment usually not required
• β-thalassemia intermedia:
• Most individuals are not transfusion-dependent in childhood, but many will become
transfusion-dependent in adulthood
• β-thalassemia major: require packed red blood cell transfusion
• Iron overload monitoring after transfusion for early detection and treatment of
hemochromatosis- iron chelating therapy (deferoxamine, deferasirox, and deferiprone)

9. • Folic acid supplements may be useful
• Hematopoietic stem cell transplant (HSCT)
• Splenectomy: in patients with hypersplenism and have a falling steady state
hemoglobin and/or a rising transfusion requirement

10. Α-THALASSEMIA
• 2 genes with 2 maternal and 2 paternal alleles control α-globin production
• Mutation or deletion takes place in chromosome 16
• four classic α thalassemia are:
• α thalassemia-2 trait, in which one of the four α-globin loci is deleted;
• α thalassemia-1 trait, with two deleted loci
• In α thalassemia-1 either cis-deletion or trans deletion occurs
• HbH disease, with three loci deleted; and
• hydrops fetalis with Hb Barts, with all four loci deleted

11. • an excess of β- and γ-globin chains are produced.
• These excess chains form Bart hemoglobin (γ4) in fetal life and HbH (β4) after birth.
• These abnormal tetramers are nonfunctional hemoglobin with very high oxygen affinity and do
not transport oxygen which result in tissue asphyxia, edema, congestive heart failure and death

12. CLINICAL FEATURES:
Severity of the diseases is based on the mutation/ deletion of α-loci
• Pallor
• Shortness of breath and easy fatiguability
• Hepatosplenomegaly
• Increased risk of infection
• Brittle bones
• Slower growth rate

13. DIAGNOSIS:
• Clinical history and examination
• Hemoglobin electrophoresis:
• Shows HbH in HbH diseases
• Blood test:
• Low MCV (microcytosis)
• Low MCH (hypochromic)
• Low hemoglobin
• Peripheral blood smear:
• Microcytosis, hypochromic anemia
• Genetic testing

14. TREATMENT:
• No treatment necessary for silent carrier and α-thalassemia trait/minor
• Packed red blood cell transfusion
• For Hbh disease when there is increased episodes of hemolysis
• For severe α-thalassemia
• Treatment of iron overload by deferoxamine