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β Thalassemia
β Thalassemia
Swati Dhungel Dibasha Adhikari Prabha Bhandari Kipa Shrestha Tutor : Dr. Sajana K.C.
Introduction
Disorder of Hemoglobin. Decreased production of globin chain. In Hemoglobinopathy, globin chains are abnormal.
Definition
Thalassemia is a heterogenous group of disorders characterized by genetically determined reduction in the rate of synthesis of normal globin chains.
Hemoglobin
Fetal Hemoglobin, HbF (2 + 2) Adult Hemoglobin, HbA (2 + 2)
Thalassemia : Etiopathogenesis
Autosomal recessive disorder. Each chromosome of chromosome number 11 has one allele for the gene to encode beta globin. Point mutation in the beta gene leads to absence or decreased production of beta globin chains.
Etiopathogenesis
- It occurs due to gene mutation. On the basis of occurrence of gene mutations thalassemias are of two types: Thalassemia - absence of globin chains + Thalassemia - decresed production of globin chains
Etiopathogenesis - + Thalassemia
Point mutation in promoter region
+ Thalassemia
Etiopathogenesis - + Thalassemia
Mutation
+ Thalassemia
Etiopathogenesis 0 Thalassemia
Point Mutation in Exon
0 Thalassemia
Etiopathogenesis 0 Thalassemia
Mutation
No Splicing
Abnormal RNA
0 Thalassemia
Mutated genes
Excess chains
Decreased HbA
Increased Erythropoietin
Increased Iron
Increased Erythropoiesis
Toxicity
Splenic Hemolysis Ineffective Erythropoiesis Bone Marrow Expansion
Hepatosplenomegaly
Fractures and Mongoloid Faces
Types
Thalassemia Minor Thalassemia Major
Thalassemia Minor
Genotype ( / +) Asymptomatic to Mild Anemia. RBCs are increased in some cases.
Thalassemia Major
Genotype (0 / 0) or, (+ / +)
globin chains are not produced at all owing to defective genes. Decreased amount of HbA, Major Red cell HbHbF The 4 tetramers are formed. RBC containing these tetramers are destroyed in Bone Marrow (Ineffective Erythropoiesis) or in Spleen. This leads to Anemia. Bone marrow becomes hyperactive to produce more RBCs.
Thalassemia Major
Hyperactive Bone Marrow
Weaker Bones
Pathological Fractures
Thalassemia Major
Bone Marrow Expands in Marrow cavity of Upper Part of Skull
Thalassemia Major
Similar expansions of marrow in facial bones give rise to RODENTS FACE or, CHIPMUNK Appearance.
Clinical Findings
Irritability Pallor Diarrhea Fever Enlarged Abdomen Cardiac failure in 1st decade of life Severe Anemia Growth Retardation Bone Changes Hepatosplenomegaly( due to extramedullary hematopoiesis) Basophilic Stippling
Fig:
Basophilic Stippling and Dacrocyte (Teardrop Cell)
Basophilic stippling /Punctate basophilia refers to an observation found when observing a blood smear in which erythrocytes display small dots at the periphery. These dots are the visualization of ribosomes.
Laboratory Findings
Severe Anemia (2-3 g/dl) Decreased Mean Cell Volume Decreased Mean Cell Hb Concentration
Laboratory Findings
Microcytic Hypochromic Picture Anisopoikilocytosis
Laboratory Findings
Target Cells
Decreased globin chains Decreased Hb
RBC loses its tensile shape Target Cells Formation of blebs in centre of RBC
Fig:
Peripheral smear from a patient with beta-zero thalassemia major showing more marked microcytosis (M) and anisopoikilocytosis (P) than in thalassemia minor. Target cells (T) and hypochromia are prominent.
Laboratory Findings
If Microcytic Hypochromic smear with nucleated RBCs is obtained from a child patients blood sample, the case is always of Thalassaemia.
Alpha Thalassemia
Absence or decreased production of alpha globin chains
Two alpha globin genes on each chromosome 16 The types of alpha thalassemia result from deletion of one or more of these genes
Clinical Syndromes
Silent carrier
Deletion of single -globin gene Not much reduction in -globin chain synthesis Individuals are completely asymptomatic
Clinical Syndromes
-thalassemia trait
Deletion of two -globin genes
Can be from the same chromosome or one from each chromosome
Clinical Syndromes
Hemoglobin H disease
Deletion of 3 -globin genes -globin synthesis markedly reduced Tetramere of beta-globin (4)- Hb H Hb-H very high affinity to O2- tissue hypoxia Hb H prone to oxidation- formation of intracellular inclusions- removed by splenic macrophages
Clinical Syndromes
Hydrops fetalis
Most severe from Deletion of all 4 globin genes In fetus, excess -globin chain form tetramere (Hb Barts)
Clinical Syndromes
Hydrops fetalis
Severe tissue hypoxia- intrauterine death Fetus- severe pallor, generalized edema, and massive hepatosplenomegaly
Clinical Syndromes
Silent carrier
Hemoglobin H disease
Hydrops fetalis