Thalassemia

Deferiprone is a recently introduced orally active iron chelator which has simplified the treatment of transfusion siderosis in thalassemia patients. Oral desferrioxamine is poorly absorbed when given orally so not preferred in the oral route.

Oral Deferiprone is a less effective alternative to injected desferrioxamine.

Deferiprone has also been indicated for acute Iron poisoning & for iron load in liver cirrhosis.

Ref: Essentials of Medical Pharmacology By KD Tripathi, 5th Edition, Pages 813-5

Increased osmotic fragility is the clinical feature of hereditary spherocytosis. 

• Stunted growth
• Bony deformities (abnormal facial structure, pathologic fractures)
• Hepatosplenomegaly
• Jaundice due to gallstones or hepatitis-related cirrhosis (or both)
• Thrombophilia

Patients with thalassemia minor or thalassemia trait have a modest anemia with hematocrit between 28% and 40%. The MCV ranges from 55 fL to 75 fL, and the red blood cell count is normal or increased. The reticulocyte count is normal or slightly elevated. The peripheral blood smear is mildly abnormal, with hypochromia, microcytosis, and target cells. In contrast to -thalassemia, basophilic stippling is present. Hemoglobin electrophoresis shows an elevation of hemoglobin A2 to 4–8% and occasional elevations of hemoglobin F to 1–5%.

HbH disease is characterised by the geno type of   – –/– ?, with the deletion of three globin loci.

HbA production is only 25–30% normal, unpaired β chains accumulate and are soluble enough to form β 4 tetramers called HbH.

HbH forms few inclusions in erythroblasts and precipitates in circulating RBC. Patients with HbH disease have thalassemia intermedia characterized by moderately severe hemolytic anemia but milder ineffective erythropoiesis. Survival into midadult life without transfusions is common.

Ref: Harrisons principles of internal medicine, 18th edition, Page: 859

Ans. is ‘c’ i.e., Thalassemia

Ans. is ‘a’ i.e., Haemoglobin

Disorders of hemoglobin

o Disorders of hemoglobin may be of two types : ‑

Qualitative defect of hemoglobin (hemoglobinopathy)

o Hemoglobinopathies are disorders of hemoglobin, characterized by a defect that results in abnormal structure of one of the globin chain of hemoglobin.

o Examples are : ‑

Sickle cell anemia, HbC, HbE, HbD-Punjab, HbO-Arab, Hb lepore.

Quantitative defect of hemoglobin

o These disorders are characterized by a defect that results in decreased rate of synthesis of one of the globin chain of hemoglobin.

o Example – Thalassemia.

Ans. is ‘b’ i.e., Splicing

Thalassemia syndrome

o Adult hemoglobin is a tetramer, composed of two a globin chains and two p glob in chains.

o Thalassemia is an inherited autosomal recessive disorder.

o In thalassemia, the genetic defect results in reduced 13 synthesis of one of the globin chains of hemoglobin.

o fl-Thalassemia is caused by deficient synthesis of I3-chain with normal a-chain synthesis.

o a-thalassemia is caused by deficient synthesis of a-chain with normal f3-chain synthesis.

o Molecular defect in pathogensis of thalassemia.

A.13-Thalassemia

o Most common type of genetic abnormality in (3-thalassemia is point mutation i.e., nonsense.

o Some may also occur due to deletion or insertion i.e., frame shift mutations.

o Defect may occur at different steps of f3-chain synthesis.

(i) Splicing mutations

• Mutations leading to aberrant splicing are the most common cause of f3-thalassemia.

(ii) Chain terminator mutations

• This cause premature termination of mRNA translation.

(iii) Promoter region mutations

• This results in transcription defect.

B. a-Thalassemia

o The most common cause of reduced a-chain synthesis is deletion of a-globin genes.

o Rarely nonsense mutation may also cause a-thalassemia.

Ans. is ‘b’ i.e., Decrease in beta chain, increase in alpha chain

o The abnormality common to all f3-thalassemias is diminshed synthesis of structurally normal 13-globin chains, coupled with unimpaired synthesis of a-chain.

o The reduced supply of f3-globin chain diminishes production of hemoglobin tetramers, causing hypochromic and microcytic anemia.

o The hematological consequences of diminished synthesis of one globin chain stem not only from low intracellular hemaglobin, but also from a relative excess of the unimpaired chain.

Consequences of thalassemia

o In f3-thalassemia, anemia is produced by two mechanisms : ‑

1.Deficit in HbA synthesis produce hypochromic microcytic anemia.

2.Excess free a-chains aggregate into insoluble inclusions within red cells and their precursors (normoblasts). These inclusions cause membrane damage that results in apoptosis of normoblasts in the marrow —> ineffective erythropoiesis. The red cells which escape death in bone marrow are prone to splenic sequestration and destruction due to cell membrane damage and decreased deformability, leading to extravascular hemolysis.

o Second mechanism is more important in producing anemia.

Ans. is ‘d’ i.e., > 3.5

T. Major                                    Intermedia                          T. Minor

J Genetics                                      Homozygous                     Double                                      Heterozygot es heterozygotes

Hb F                                            30-90%                                (20-100%)                                              0-5%

) HbA₂                                           < 3.5%                                  <3.5%                                                          3.6 –8%

Ans. is d  i.e., Hb – Electrophoresis

o Hemoglobin electrophoresis should always be the first investigation to include/exclude the diagnosis of thalasemia. o The level of normal adult hemoglobin HbA is markedly decreased with proportionate increase in HbA2 and HbF. X-ray findings in thalassemia

1. Crew cut appearance
2. Hair on end appearance

Ans. is ‘a’ i.e., Thalassemia

o NESTROFT ( Naked Eye Single Tube Red Cell Osmotic Fragility Test) is a screening test for detection of beta thalassemia trait.

Thalassemia screening

o Widespead prevalence of thalessemia has led to a pressing demand for community screening.

o Various methods for screening of thalassemia trait are available which include peripheral smear examination, RBC indices, Meintzer’s fraction, discriminant functions, NESTROFT etc.

o NESTROFT TEST is used in many centres in India for screening of thalassemia trait.

o If mother is NESTROFT positive, the confirmatory test for HbA₂ is done for mother and the father is subjected to

screening by NESTROFT. If father is also NESTROFT positive, confirmatory test for HbA2 is done for father. o If both the parents have thalessemia trait, there is 1:4 chance of fetus having thalassemia major. o Therefore, prenatal diagnosis is done by chorionic villus sampling (CVS) in first trimester.

o If CVS confirms the fetus to be having thalasemia major, termination of pregnancy is indicated after counseling the parents.

o If the fetus has thalassemia minor (trait), pregnancy is continued as such and baby will have normal lifespan.

o It is worth noting here that a positive NESTROFT test is seen in other conditions beside beta thalassemia trait.

These are iron deficiency anemia, alpha thalassemia trait, homozygous and heterozygous HbE, HbS as well as hereditary persistence of fetal hemoglobin.

o Therefore, a positive NESTROFT test should always be followed by a confirmatory test for HBA₂ (eg. serum electrophoresis).

Ans. is ‘b’ i.e., No a-chain

Alpha – Thalassemia

o People who do not produce enough alpha globin chain have alpha – thalassemia.

o Alpha globin chain is made by four genes, each gene contributes to 25% of the a-globin chains.

o The severity of a-thalassemia varies greatly depending on the number of a-globin genes affected : –

(i)       Silent carrier state o Single a-globin gene is deleted.

o These individuals are completely asymptomatic

(ii) a-Thalassemia trait o Two a-globin genes are deleted.

o These individuals are asymptomatic with some red cell abnormalities like 13-thalassemia minor.

(iii)  HbH disease

o Three genes of a-globin chain are deleted.

o With only one gene, the synthesis of a-chain is markedly reduced and tetramers of excess 0-globin, called HbH, form.

o HbH has extremely high affinity for oxygen and therefore is not useful for oxygen exchange, leading to tissue hypoxia disproportionate to the level of hemoglobin.

o Patients have moderate to severe anemia that may require occasional blood transfusion.

(iv)   Hydrops fetalis

o Deletion of all four a-globin genes.

o In the fetus, excess It-globin chains form tetramers, known as hemoglobin Barts.

o Hemoglobin Bart has such a high affinity for oxygen that it delivers almost no oxygen to tissues. o Most individuals die before or shortly after birth.

o In utero blood transfusion have allowed the birth of children with hydrops fetalis who then require lifelong blood transfusion.

Ans. is ‘c’ i.e., Malaria

Types of anemia, that have protective effect against R falciparum malaria : –

G6PD deficiency, Sickle cell anemia, Thalassemia, HbC, Pyruvate kinase deficiency

Ans. is ‘a’ i.e., Thalassaemia; ‘b’ i.e., Hb-Lepore; ‘c’ i.e., Hb Bart’s

of Microcytic hypochromic anemia                                                              

o Iron deficiency anemia                                                o Alpha and Beta thalassemia

o Anemia of chronic disease                                           o Hemoglobin C syndrome

o Sideroblastic anemia (Lead intoxication)                 o Hemoglobin ‘ S’ syndrome

Note :

o Hb Bart’s is the most severe form of a-thalassemia.

o In Hb Lepore, there is nonhomologus fusion of p and 6 genes and forms an abnormal haemoglobin with total absence of normal (3-chain. It is one of the form of (3-thalassemia minor.

Ans. is ‘a’ i.e., Thalassemia; ‘c’ i.e., Anemia in chronic disease

Ans. is ‘b’ i.e., (3-Thalassemia

Ans. is ‘b’ i.e., No 13 chain

Ans. is ‘a’ i.e., HbA₂

Hemoglobin electrophoresis is classically associated with elevated HbA₂

Ans. is ‘b’ i.e., Oral deferiprone

Desferrioxamine is poorly absorbed from GIT and hence not recommended for oral administration, although it continues to be the chelating agent of choice for parentral administration.

o Deferiprone is a recently introduced orally active iron chelating agent meant to be used as an alternative to injected desferrioxamine.

o Oral Deferiprone is prefered over oral desferrioxamine.

Remember

o For acute iron poisoning desferioxamine is the DOC.

o For chronic iron overload, e.g. thalassemia, oral deferipone is the DOC.

Ans. is ‘b’ i.e., Splicing

Thalassemia syndrome

o Adult hemoglobin is a tetramer, composed.of two a globin chains and two 13 globin chains. o Thalassemia is an inherited autosomal recessive disorder.

o In Thalassemia, the gentic defect results in reduced synthesis of one of the globin chains of hemoglobin. o – Thalassemia is caused by deficient synthesis of 13-chain with normal a-chain synthesis. o a – thalassemia is caused by deficient synthesis of a-chain with normal 13-chain synthesis. o Molecular defect in pathogenesis of thalassemia.

A) 13-thalassemia

o Most common type of genetic abnormality in 13-thalassemia is point mutation, i.e. nonsense. o Some may also occur due to deletion or insertion i.e. framshift mutations.

o Defect may occur at different steps of [3-chain synthesis –

I’) Splicing mutations

• Mutations leading to aberrant splicing are the most common cause of (3-thalassemia.

ii) Chain terminator mutations

• This cause premature termination of mRNA translation.

iii) Promoter region mutations

• This results in transcription defect

B) a-thalassemia

o The most common cause of reduced a-chain synthesis is deletion of a-globin genes.

o Rarely nonsense mutation may also cause a-thalassemia.

Ans. is ‘a’ i.e., THbF; ‘b’ i.e., THbA₂; ‘c’ i.e, Microcytosis

There are three forms of beta-thalassemia

Thalassemia major (Cooley’s anemia)

o The individual with thalassemia major is homozygous for beta-thalassemia genes.

o It is severe transfusion dependent anemia.

o Severe anemia manifests 6-9 months after birth, as hemoglobin synthesis switches from HbF to HbA.

Thalassemia minor (beta-thalassemia trait)

o The individual with thalassemia minor has only one copy of the beta thalassemia gene, i.e. they are heterozygous for beta-thalassemia genes.

o This is mildest form with mild or absent anemia.

o Patients are usually asymptomatic, and are typically identified during laboratory investigations.

Thalassemia intermedia

o Thalassemia intermedia is a condition intermediate between the major and minor forms.

o Affected individuals can often manage a normal life but may need occasional transfusion.

Hematological findings in Thalassemia

• Peripheral blood smear

          Anisocytosis (variation in size of RBCs)             Target cells (hemoglobin collects in the center of the red cells)

          Poikilocytosis (variation in shape of RBCs)        Basophilic stippling

          Microcytic hypochromic RBCs                            Fragmented RBC

Ans. is ‘d’ i.e.,> 3.5

Nestrof test

o This test is being widely used in India and other developing countries in thalassemia screening programmes. o The cases which are positive, subjected to HbA2 estimation for confirmation of thalassemia trait.

Ans. is ‘c’ i.e. HbA₂

Hemoglobin A2

o In hemoglobin A., the polypepties consists of two a and two 8 chains i.e. the p chain of the normal adult hemoglobin is replaced by the 8 chain.

o In normal adults hemoglobin A₂ is present in trace amounts. It accounts for 1.5% to 3.5% of the normal adult hemoglobin.

Clinical implication of HbA2

o HbA2 levels have special application in the diagnosis of beta thalassemia trait.

Elevation of HbA, is present in these cases even through the peripheral blood smear is normal.

Microcytosis and other morphological characteristic of [3-thalassemia trait are also seen in iron deficiency but unlike 3 thalassemia trait HbA₂ level is decreased.

Ans. is ‘c’ i.e., Hb electrophoresis

`The diagnosis of thalassemia syndromes is best established by Hb electrophoresis.’

Ans. is ‘d’ i.e. increased osmotic fragility

Osmotic fragility test

o Red cells are suspended in a series of tubes containing hypotonic solutions of NaC1 varying from .9% to 0.0% incubated at room temperature, for 30 minutes and centrifuged.

o The percent hemolysis in the supernatant solution is measured and plotted for each NaC1 concentration.

o Cells that are more spherical, with a decreased surface/volume ratio have a limited capacity to expand in hypotonic solutons and lyse at a higher concentration of Nacl than do normal biconcave cells. o These cells are said to have increased osmotic fragility and are seen in hereditary spherocvtosis

o Conversely, cells that are hypochronic and flatter have a greater capacity to expand in hypotonic solutions, lyse at lower concentration, are said to have decreased osmotic fragility.

o These cells with increased surface/volume ratio are osmotically resistant and are seen in iron deficiency, thalassemia, liver disease and reticulocytosis.

Ans. is ‘a’ i.e., Thalassemia

*  NESTROFT ( Naked Eye Single Tube Red Cell Osmotic Fragility Test) is a screening test for detection of beta thalassemia trait.

Thalassemia screening

*  Widespead prevlence of thalessemia has led to a pressing demand for community screening.

*  Various methods for screening of thalassemia trait are available which include peripheral smear examination, RBC indices, Meintzer’s fraction, discriminant functions, NESTROFT etc.

*  NESTROFT TEST is used in many centres in India for screening of thalassemia trait.

*  If mother is NESTROFT positive, the confirmatory test for HbA2 is done for mother and the father is subjected to

screening by NESTROFT. If father is also NESTROFT positive, confirmatory test for HbA2 is done for father.

* If both the parents have thalessemia trait, there is 1:4 chance of fetus having thalassemia major.

* Therefore, prenatal diagnosis is done by chorionic villus sampling (CVS) in first trimester.

* If CVS confirms the fetus to be having thalasemia major, termination of pregnancy is indicated after counseling the parents.

*  If the fetus has thalassemia minor (trait) pregnancy is continued as such and baby will have normal lifespan.

*  It is worth noting here that a positive NESTROFT test is seen in other conditions beside beta thalassemia trait.

These are iron deficiency anemia, alpha thalassemia trait, homozygous and heterozygous HbE, HbS as well as hereditary persistence of fetal hemoglobin.

Therefore, a positive NESTROFT test should always be followed by a confirmatory test for HBA2 ( eg. serum electrophoresis).

Ans. is ‘a’ i.e., Thalassemia

Bone Changes in Thalassemia

1. Bones become thin and pathological fracture may occur.

2. Massive expansion of the marrow of face and skull produces characteristics facies.

3. Severe maxillary hyperplasia and malocclusion.

4. Prominant widening of diploic spaces with “hair on end appearance” caused by vertical trabeculae.

5.  Crew-cut appearance —> striking expansion of hematopoietically active marrow that erodes existing cortical bone and induces new bone formation giving rise to crew cut appearance.

Causes of “Hair on end appearance” —> Sickle cell anemia, Hereditary spherocytosis, G-6-PD deficiency

Ans. is ‘b’ i.e., alpha-thalassemia

o Out of the given 4 types of hemolytic anemias only alpha thalassemia is able to give rise to such severe presentation at birth. In all other conditions the newborn is either normal or has mild jaundice.

Ans. is ‘d’ i.e., Increased osmotic fragility

Ans. is ‘a’ i.e. ITP; ‘b’ i.e. Thalassemia & ‘c’ i.e. Hereditary spherocytosis 

Schwartz writes about Postsplenectomy infections ” Reason for splenectomy is the single most influential determinant of OPSI risk. Case series demonstrate that those who undergo splenectomy for hematologic disease (malignancy, myelodysplasia, or hemoglobinopathy) are far more susceptible to OPSI than patients who undergo splenectomy for trauma or iatrogenic reasons. Age is also an important consideration, with children 50 years being at elevated risk.”

Ans. is ‘b’ i.e., Thalasemia major 

Answer is C (Thalassemia)

Erythrocyte protoporphyrin levels are characteristically normal in Thalassemia

Free Erythrocyte Protoporphyrin is a useful screening test for microcytic hypochromic anemias. Free Erythrocyte protoporphyrin levels are increased in iron deficiency anemias, lead poisoning many cases of sideroblastic anemia and anemias of chronic disease. Erythrocyte protoporphyrin levels are normal in Thalassemias.

Answer is D (All of the above)

Decreased haptaglobin levels may occur in all cases of hemolysis.

Although decreased haptaglobin levels are more characteristic of intravascular hemolysis, decreased levels are also seen in cases of extravascular hemolvsis.

Heptaglobin levels and hemolysis (Hematology for Student’s by Mackinney (2003)/78, 79

• Normal plasma contains haptoglobin, an a2- globulin that can bind free haemolglobin
• During intravascular hemolysis as levels of free haemoglobin rise significantly, the levels of serum haptoglobin are observed to be very low or absent
• Even in Extravascular hemolysis, enough haemoglobin levels leaks out of the macrophages to bind with and deplete haptaglobin

Therefore

A low serum haptaglobin concentration is a good test of hemolysis butt is not specific for intravascular hemolysis.

Answer is D (0%) :

Thallassemia follows an autosomal recessive inheritance.

The risk of thallasemmia major in a child of normal (HbA2 : 2-3) and thallassemia minor (HbA₂ = 4.8%) parents is zero%.

Ans. B: Autosomal recessive

Thalassemia is an inherited autosomal recessive blood disease. Some other autosomal recessive disorders:

• Cystic fibrosis
• Phenylketonuria
• Galactosemia
• Wilsons disease
• Sickle cell anemia
• Ehler-Danlos syndrome
• Friedreich ataxia

Ans. A: Increased HbA2

Ans. B: Normal HbF and normal HbA2

Alpha (+) thalassemia – genetic mutations that result in decreased production of alpha-globin usually due to the functional deletion of 1 of the 4 alpha globin genes. Based on the number of inherited alpha genes, it is subclassified into 3 general forms:

• Thalassemia (-u/ a a) is characterized by inheritance of 3 normal a-genes. These patients are referred to clinically as silent carrier of alpha thalassemia. Other names for this condition are alpha thalassemia minima, alpha thalassemia-2 trait, and heterozygosity for alpha (+) thalassemia minor. The affected individuals exhibit no abnormality clinically and may be hematologically normal or have mild reductions in red cell mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH).
• Inheritance of 2 normal alpha genes due to either heterozygosity for alpha (0) thalassemia (u a/ —) or homozygosity for alpha (+) thalassemia (-u/-a) results in the development of alpha thalassemia minor or alpha thalassemia-1 trait. The affected individuals are clinically normal but frequently have minimal anemia and reduced mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH).
• Inheritance of one normal alpha gene (-a/ —) results in abundant formation of hemoglobin H. This condition is known as ElbH disease. The affected individuals have moderate to severe lifelong hemolytic anemia, modest degrees of ineffective erythropoiesis, splenomegaly and variable bony changes
• Persons with alpha-thalassemia traits have normal HbA2 and HbF levels whereas beta- thalassemia patients have elevated HbA2

Ans. Thalasemia

Ans. Thalassemia

Ans. is ‘a’ i.e., Thalassemia

Thalassemia Syndromes :‑

The thalassemia syndromes are a heterogeneous group of disorders caused by inherited mutations that decrease the synthesis of either the a-globin or (3-globin chains that compose adult hemoglobin, HbA (a2(32), leading to anemia, tissue hypoxia, and red cell hemolysis related to the imbalance in globin chain synthesis.

Ans. is ‘a’ i.e., Alpha chain deficiency

Alpha-thalassemia

People who do not produce enough alpha globin chain have alpha – thalassemia. Alpha globin chain is made by four genes, each gene contributes to 25% of the a-globin chains. The severity of a-thalassemia varies greatly depending on the number of a-globin genes affected –

• Silent carrier state
• Single a-globin gene is deleted. These individuals are completely asymptomatic.
• a-thalassemia trait
• Two a-globin genes are deleted. These individuals are asymptomatic with some red cell abnormalities like β-thalassemia minor.
• HbH disease
• Three genes of a-globin chain are deleted. With only one gene, the synthesis of a-chain is markedly reduced and tetramers of excess β-globin, called HbH, form. HbH has extremely high affinity for oxygen and therefore is not useful for oxygen exchange, leading to tissue hypoxia disproportionate to the level of hemoglobin. Patients have moderate to severe anemia that may require occasional blood transfusion.
• Hydrops fetalis
• There is deletion of all four a-globin genes. In the fetus, excess y-globin chains form tetramers, known as hemoglobin harts. Hemolgobin bart has such a high affinity for oxygen that it delivers almost no oxygen to tissues. Most individuals die before or shortly after birth. In utero blood transfusion have allowed the birth of children with hydrops fetalis who then require life long blood transfusions.

Defective splicing (defect in snurps) is the most common mutation causing thalassemia.

• Molecular defect in pathogensis of thalassemia:‑

A) β-Thalassemia

• Most common type of genetic abnormality in β-thalassemia is point mutation i.e., nonsense.
• Some may also occur due to deletion or insertion i.e., frame shift mutations.
• Defect may occur at different steps of β-chain synthesis:

i) Splicing mutations

• Mutations leading to aberrant splicing are the most common cause of P-thalassemia.

ii) Chain terminator mutations

• This cause premature termination of mRNA translation.

iii) Promoter region mutations

• This results in transcription defect.

B) α-Thalassemia

• The most common cause of reduced a-chain synthesis is deletion of a-globin genes.
• Rarely nonsense mutation may also cause a-thalassemia.

Thalassemia is an inherited blood disorder in which the body makes an abnormal form of hemoglobin. Hemoglobin is the protein molecule in red blood cells that carries oxygen.

The disorder results in excessive destruction of red blood cells, which leads to anemia. Anemia is a condition in which your body doesn’t have enough normal, healthy red blood cells.

Thalassemia is inherited, meaning that at least one of your parents must be a carrier of the disease. It’s caused by either a genetic mutation or a deletion of certain key gene fragments.

Thalassemia minor is a less serious form of the disorder. There are two main forms of thalassemia that are more serious. In alpha thalassemia, at least one of the alpha globin genes has a mutation or abnormality. In beta thalassemia, the beta globin genes are affected.

Ans. is ‘d’ i.e., Thalassemia

Leucoervthroblastosis refers to the presence of a variable number of immature erythroid and myeloid cells in circulation.

• The blood film shows the presence of erythroblasts and granulocyte precursors (e.g. myelocytes and myeloblasts).
• It is seen in primary myelofibrosis and is frequent when there is marrow infiltration by tumour.
• This disturbs the marrow infrastructure and allows early release of the precursor.

Causes of leuco-erythroblastosis

Ans. is ‘a’ i.e., Thalassemia

The thalassemia syndromes are a heterogeneous group of disorders caused by inherited mutations that decrease the synthesis of either the c-globin or p-globin chains that compose adult hemoglobin, HbA (c2p2), leading to anemia, tissue hypoxia, and red cell hemolysis related to the imbalance in globin chain synthesis.

Ans. is ‘d’ i.e., Raised HbA₂

• An abnormal increase in the level of HbA₂ is the most significant parameter in the diagnosis of beta-thalassemia carriers. HbA-2 is constanly elevated in heterozygous carriers of [3-thalassemia in all the ethnic groups studied. The values range from 3^.5 to 7%.

Investigations in thalassemia

• Hemoglobin electrophoresis should always be the first investigation to include/exclude the diagnosis of thalasemia. The level of normal adult hemoglobin HbA is markedly decreased with proportionate increase in HbA2 and HbF.
• X-ray skull shows :‑

i)         Crew-cut appearance

ii)       Hair on end appearance

Ans. is ‘d’ i.e., Alpha thalassemia silent carrier

Ans. is ‘a’ i.e., Intron 1 inversion

• Thalassemias are autosomal recessive disorder
• The most common mutation causing 13 thalassemias is intron/inversion

Also know:

Synthesis of alpha chain is controlled by 2 gene clusters on  →    Chromosome 16

Synthesis of beta chain is controlled by 2 gene clusters on   →     Chromosome 11

Thalassemia mutations in India

Ans. c. Beta-thalassemia