Thalassemias

Question 1

Thalassemia’s other names

Answer 1

Hereditary leptocytosis, Mediterranean anemia

Question 2

Cause of Thalassemia

Answer 2

Reduction or total absence of synthesis of one or more globin chains

Question 3

Most clinically significant mutations

Answer 3

α-globin and β-globin gene mutations

Question 4

Geographic distribution of Thalassemia belt

Answer 4

Thalassemia belt extends from Mediterranean to Southeast Asia and Northern Africa

Question 5

Relation to malaria

Answer 5

Thalassemia minor imparts resistance to malaria

Question 6

Clinical findings suggesting Thalassemia

Answer 6

Pallor (due to anemia), jaundice (due to hemolysis), splenomegaly (due to sequestration and hemolysis), skeletal deformities (due to bone marrow expansion)

Question 7

Thalassemia findings in untreated β-thalassemia major

Answer 7

More prominent skeletal deformities due to massive expansion of bone marrow cavities

Question 8

Cause of clinical manifestations in Thalassemia

Answer 8

Decreased or absent production of globin chains, unequal production causing imbalance in α/β chain ratio

Question 9

Effect of α/β chain imbalance in Thalassemia

Answer 9

Leads to marked decreased survival of erythrocytes and their precursors

Question 10

Mechanism of shortened RBC survival in Thalassemia

Answer 10

α/β chain imbalance determines clinical severity, different mechanisms in β-thalassemia and α-thalassemia

Question 11

Complete Blood Count (CBC) expected findings in Thalassemia

Answer 11

↓ Hb, ↓ Hct, ↓ MCV, ↓ MCH, ↓ MCHC, Slight to moderate ↑ Reticulocyte count

Question 12

Peripheral Blood Smear findings in Thalassemia

Answer 12

Varying degrees of microcytosis, hypochromia, target cells, anisocytosis, NRBCs, poikilocytosis, RBC inclusions (basophilic stippling, Howell-Jolly bodies, Pappenheimer bodies, Hb H inclusion bodies)

Question 13

Iron studies in Thalassemia (to rule out IDA)

Answer 13

Serum ferritin and serum iron: Normal or ↑, TIBC: Normal

Question 14

Confirmatory tests for Thalassemia

Answer 14

Molecular genetic tests

Question 15

Alpha Thalassemia cause

Answer 15

Typically caused by a deletion of one, two, three, or all four of the α-globin genes, resulting in reduced or absent production of α chains

Question 16

Normal genotype for Alpha Thalassemia

Answer 16

aa/aa

Question 17

Silent carrier state in Alpha Thalassemia

Answer 17

One out of four genes deleted, genotype: -a/aa, asymptomatic

Question 18

Two of four genes deleted (–/aa or -a/-a), mild microcytic hypochromic anemia

Answer 18

Alpha Thalassemia Trait (a-thalassemia minor)

Question 19

Three of four genes deleted (–/-a), microcytic hypochromic anemia

Answer 19

Hb H Disease

Question 20

Hb H disease predominantly seen in neonates

Answer 20

Hb Bart

Question 21

Most severe form of alpha thalassemia, caused by deletion of all four alpha globin genes (–/–)

Answer 21

Hb Bart hydrops fetalis syndrome (alpha thalassemia)

Question 22

Fetus survival in Hb Bart syndrome

Answer 22

Rare survival with intrauterine transfusion and neonatal intensive care

Question 23

Survivors of Hb Bart syndrome

Answer 23

May require severe transfusion-dependent anemia treatment like β-thalassemia major

Question 24

Treatment options for Hb Bart syndrome

Answer 24

Bone marrow transplant or cord blood transplant may be helpful

Question 25

Beta thalassemia mutation cause

Answer 25

Mutations in β-globin gene complex

Question 26

Normal genotype for β-globin gene

Answer 26

B/B

Question 27

Silent carrier state in β-thalassemia genotype

Answer 27

β silent / β

Question 28

β-thalassemia trait genotype

Answer 28

β+ / β or β0 / β

Question 29

Silent carrier β-thalassemia remarks

Answer 29

Asymptomatic, normal hematologic parameters

Question 30

β+ / β or β0 / β remarks

Answer 30

Asymptomatic, mild hemolytic anemia, microcytic, hypochromic RBCs

Question 31

Most severe form of beta thalassemia genotype

Answer 31

β+ / β+ or β0 / β0

Question 32

β-thalassemia major (Codey's anemia) characteristics

Answer 32

Severe hemolytic anemia, microcytic, hypochromic RBCs, transfusion-dependent

Question 33

Peripheral blood smear findings in β-thalassemia major

Answer 33

Target cells, teardrop cells, elliptocytes, nucleated red cells, polychromasia, basophilic stippling, Howell-Jolly bodies, Pappenheimer bodies

Question 34

β-thalassemia major patient features

Answer 34

Frontal bossing, prominence of cheekbones and upper jaw, 'hair on end' skull appearance

Question 35

Cause of iron accumulation in β-thalassemia major

Answer 35

Regular RBC transfusions

Question 36

β-thalassemia intermedia genotypes

Answer 36

βsilent / βsilent, β+ / βsilent, β0 / βsilent

Question 37

Clinical symptoms of β-thalassemia intermedia

Answer 37

Moderate symptoms, transfusion-independent, mild to moderate hemolytic anemia, microcytic, hypochromic RBCs

Question 38

Definition of β0 mutation

Answer 38

β-globin gene mutation where no β chains are produced

Question 39

Definition of β+ mutation

Answer 39

β-globin gene mutation resulting in 5% to 30% reduction in β chain production

Question 40

Definition of βsilent mutation

Answer 40

β-globin gene mutation causing mildly decreased β chain production