Thalassemias: Genetic Disorders of Hemoglobin

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Questions and Answers

What percentage of Hemoglobin S (Hb S) would result in a positive solubility screening test?

30%

40%

20% (correct)

10%

Which hemoglobin types and percentages are typically shown in hemoglobin electrophoresis for someone with Hb S?

Hb A = 60%, Hb S = 40% (correct)

Hb A = 70%, Hb S = 30%

Hb A = 80%, Hb S = 20%

Hb A = 50%, Hb S = 50%

When are sickle cells typically seen in a peripheral blood smear?

During sickle cell crises (correct)

Never present

Only when there is severe dehydration

Always present in individuals with sickle cell trait

What amino acid replaces glutamic acid at the 6th position of the β chain in Hemoglobin C disease?

Lysine Signup and view all the answers

Which statement is true regarding hemoglobin electrophoresis of Hemoglobin C (Hb C) at alkaline pH?

Hb C migrates with Hb A₂ Signup and view all the answers

What is the primary cause of alpha thalassemia?

Gene deletion Signup and view all the answers

Which type of thalassemia results from a defect in the rate of synthesis of beta chains?

Beta thalassemia Signup and view all the answers

How many genes are involved in making the alpha hemoglobin chain?

4 Signup and view all the answers

Which thalassemia condition is also known as Cooley Anemia?

Beta Thalassemia Major Signup and view all the answers

Where is the gene for the beta chain located?

Chromosome 11 Signup and view all the answers

What typically causes Beta Thalassemia?

Point mutation Signup and view all the answers

Why doesn't beta thalassemia manifest at birth?

Presence of predominant Hb F Signup and view all the answers

What characterizes the silent carrier state of beta thalassemia?

Mild mutation Signup and view all the answers

Which genotype is associated with β thalassemia major?

βο/βο Signup and view all the answers

What clinical severity is typically observed in individuals with the genotype β/βο?

Silent Signup and view all the answers

In the pedigree chart, which condition does the first child exhibit?

β thalassemia trait Signup and view all the answers

Which classification of β thalassemia is associated with moderate anemia?

β thal intermedia Signup and view all the answers

What is the expected clinical severity in an individual with the genotype β+/β+?

Moderate Signup and view all the answers

What genotype does the mother in the pedigree chart have?

β β+ Signup and view all the answers

What is the characteristic genotype of a silent carrier of β thalassemia?

β/β+ Signup and view all the answers

Which child in the pedigree chart does not have any form of anemia?

Third child Signup and view all the answers

What kind of anemia is characteristic of Beta-Thalassemia?

Microcytic, hypochromic anemia Signup and view all the answers

Which type of cells are most commonly seen in the peripheral blood of Beta-Thalassemia patients?

Target cells Signup and view all the answers

What is a common complication of regular transfusions in Beta-Thalassemia patients?

Iron overload Signup and view all the answers

Which hemoglobin type is most commonly elevated in Beta-Thalassemia patients?

Hb F Signup and view all the answers

What physical features are associated with Beta-Thalassemia?

Protrusion of upper teeth and mongoloid facial features Signup and view all the answers

Which of the following is not a hazard of transfusion treatment in Beta-Thalassemia?

Hyperproliferation of erythrocytes Signup and view all the answers

What is the predominant cause of alpha thalassemia?

Alpha globin chain gene deletion Signup and view all the answers

How many alpha globin chain genes are located on chromosome 11?

4 Signup and view all the answers

What condition results from the presence of only one functional alpha globin gene?

Hemoglobin H disease Signup and view all the answers

Which clinical condition corresponds to the genotype aa/--?

Alpha thalassemia trait Signup and view all the answers

What results from the absence of alpha chains during fetal life?

Increase in gamma chains Signup and view all the answers

Which genotype corresponds to Bart's hydrops fetalis syndrome?

--/-- Signup and view all the answers

What is a key characteristic of Beta-thalassemia?

Less hemoglobin is made resulting in too few red blood cells Signup and view all the answers

Which of the following is NOT a lifestyle tip for managing thalassemia?

Engage in strenuous physical exercise Signup and view all the answers

Which type of red blood cells are affected in Sickle Cell Disease?

Stiff and misshapen red blood cells Signup and view all the answers

When is World Thalassemia Day celebrated?

8th May Signup and view all the answers

Which disorder involves a gene deletion affecting only delta and beta genes?

Delta Beta Thalassemia Signup and view all the answers

What is the hemoglobin type predominantly found in homozygous cases of Delta Beta Thalassemia?

Hb F Signup and view all the answers

Which condition is characterized by a gene deletion causing hemoglobinopathy and Bart's hydrops fetalis?

Hemoglobin Lepore Signup and view all the answers

Which type of thalassemia results from the presence of two altered HBB genes?

Sickle Cell Signup and view all the answers

What physical examination finding indicates hemolysis in thalassemia patients?

Jaundice Signup and view all the answers

Which of the following is a common symptom of thalassemia?

Dark urine Signup and view all the answers

Which parameter differentiates thalassemia from iron deficiency anemia in carrier states?

Elevated RBC count with decreased MCV, normal RDW Signup and view all the answers

What does a PB stained smear typically show in thalassemia major?

Many target cells and basophilic stippling Signup and view all the answers

What is a key clinical feature of beta thalassemia major?

Skeletal deformity Signup and view all the answers

Which lab finding is typical in thalassemia minor or trait?

Normal to slightly decreased MCHC Signup and view all the answers

What happens when brilliant cresyl blue stain is used for a prolonged period?

Hb H precipitates Signup and view all the answers

Which staining method is based on the Kleihauer-Betke procedure?

Acid elution stain Signup and view all the answers

Which of these conditions is diagnosed with the presence of only one gene producing alpha chains?

Hemoglobin H Disease Signup and view all the answers

What is a characteristic feature of the silent carrier state for β thalassemia?

Only a small decrease in production of beta chains Signup and view all the answers

Which condition results in a baby born with hydrops fetalis?

Bart's Hydrops Fetalis Syndrome Signup and view all the answers

Which of the following hemoglobins remains in cells when subjected to acid elution staining?

Hb F Signup and view all the answers

What is the typical hemoglobin range observed in individuals with beta thalassemia minor?

10-13 g/dL Signup and view all the answers

Which of the following is characterized by mild microcytic, hypochromic anemia?

Alpha Thalassemia Trait Signup and view all the answers

Which feature is useful for differentiating HPFH from beta thalassemia?

Acid elution stain Signup and view all the answers

Which characteristic appearance do RBCs exhibit in Hb H disease when stained with brilliant cresyl blue?

Golf ball appearance Signup and view all the answers

What is the typical hemoglobin composition for an adult with Hemoglobin H Disease?

10-20% Hemoglobin H (beta4) Signup and view all the answers

Which type of beta thalassemia can occur with either heterozygous or homozygous mutations?

Beta thalassemia intermedia Signup and view all the answers

Which condition is the most severe form of alpha thalassemia and is incompatible with life?

Bart's Hydrops Fetalis Syndrome Signup and view all the answers

Which diagnostic method is used to differentiate various forms of thalassemia and hemoglobinopathies?

Hemoglobin electrophoresis Signup and view all the answers

Which hemoglobin types are increased in beta thalassemia intermedia?

Hb A2 and Hb F Signup and view all the answers

Which of the following is NOT typically seen in a peripheral blood smear of someone with thalassemia major?

High RBC count Signup and view all the answers

Which clinical condition is related to the observation of marked bone changes due to expansion of marrow space?

Beta thalassemia major Signup and view all the answers

In which condition are there usually no hematologic abnormalities and the diagnosis requires genetic mapping?

Silent Carrier State Signup and view all the answers

What is a common differential diagnosis for beta thalassemia minor?

Iron deficiency anemia Signup and view all the answers

Which beta thalassemia type typically requires transfusions only under stress conditions like pregnancy or infection?

Beta thalassemia intermedia Signup and view all the answers

What differentiates Alpha Thalassemia Trait from iron deficiency anemia?

Low MCV and elevated RBC count Signup and view all the answers

Which of the following is a common presentation in infants with beta thalassemia major?

Failure to thrive and pallor Signup and view all the answers

Study Notes

Thalassemias

Diverse group of disorders that manifest as anemia of varying degrees
Result in defective production of globin chain of Hb molecule
Distribution is worldwide
May be either homozygous defect or heterozygous defect
Globin chains are structurally normal, but have imbalance in production of the two types of globin chains
Results in overall decrease in amount of Hb produced and may induce hemolysis

Types of Thalassemias

Alpha (α) thalassemia: caused by defect in rate of synthesis of alpha chains
Beta (β) thalassemia: caused by defect in rate of synthesis of beta chains

Genetics of Thalassemia

Adult hemoglobin is composed of two alpha and two beta chains
Alpha thalassemia usually caused by gene deletion; Beta thalassemia usually caused by point mutation

Alpha Thalassemia

4 genes are involved in making the alpha hemoglobin chain
Classification of alpha thalassemia:
- Silent carrier state: deletion of one alpha gene
- Alpha thalassemia trait: deletion of two alpha genes
- Hemoglobin H disease: deletion of three alpha genes
- Bart's hydrops fetalis syndrome: deletion of four alpha genes

Beta Thalassemia

2 genes are involved in making the beta hemoglobin chain
Classification of beta thalassemia:
- Beta thal minor/trait: heterozygous genotype
- Beta thal intermedia: homozygous genotype
- Beta thal major: homozygous genotype with two mutated beta-globin genes

Characteristics of Beta Thalassemia

Severe microcytic, hypochromic anemia
Peripheral blood smear shows:
- Markedly hypochromic, microcytic erythrocytes
- Extreme poikilocytosis
- Target cells, teardrop cells, and elliptocytes
- Basophilic stippling and numerous NRBCs
High reticulocyte count (2-8%)
Most of hemoglobin present is Hb F with or without slight increase in HbA2

Complications of Beta Thalassemia

Excessive number of transfusions results in iron overload and hemosiderosis
Without iron chelation, patients develop cardiac disease

Treatment of Beta Thalassemia

Transfusion is the main line of treatment
Carries the following hazards:
- Development of iron overload
- Development of alloimmunization
- Risk of transfusion-transmitted diseases

Lifestyle Tips for Thalassemia

Avoid excessive iron
Eat a healthy diet
Avoid infections
Get annual flu shots and Hepatitis B vaccines

Other Defects in the Beta-Cluster Gene

Delta Beta Thalassemia
Hemoglobin Lepore
Hereditary Persistence of Fetal Hemoglobin (HPFH)

Delta Beta Thalassemia

Group of disorders due to gene deletion that removes or inactivates only delta and beta genes
Clinically similar to beta thalassemia minor when heterozygous and beta thalassemia intermedia when homozygous

Hemoglobin Lepore

Rare class of thalassemia caused by a gene deletion in a beta locus on the chromosome
Characterized by a silent carrier, alpha thalassemia, hemoglobinopathy, and Bart's hydrops fetalis

World Thalassemia Day

Celebrated on May 8th

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Description

Learn about thalassemias, a group of genetic disorders that affect the production of hemoglobin, leading to anemia and other complications. Understand the causes, types, and characteristics of thalassemias.