Hemoglobinopathies — MCQs

10 questions

The primary defect which leads to sickle cell anemia is:

A child presents with recurrent chest infections and abdominal pain. There is a history of 1 blood transfusion in the past. On examination, he had icterus and mild splenomegaly. Electrophoresis shows increased HbA2, HbF, and S spike. What is the likely diagnosis?

Which of the following has Autosomal Recessive inheritance?

A 22-year-old male with a known history of sickle cell disease presents with sudden onset chest pain, dyspnea, and cyanosis. What is the most likely diagnosis and the immediate treatment?

Which of the following statements about hemoglobin is true?

In sickle cell anemia, the mutation at codon 6 results in the substitution of which amino acid?

A 25-year-old lady presented with anemia, jaundice, and recurrent joint pains. All of the following are true except:

Which of the following conditions is the classic example of acute intravascular hemolysis triggered by oxidative stress?

Which of the following are secondary iron overload conditions? I. Transfusion related iron load II. Thalassemia III. Hepatitis C associated liver disease Select the correct answer using the code given below :

Q10

Which of the following treatments are recommended for a pregnant woman suffering from sickle cell disease ? I. Folic acid 1 mg daily II. Azathioprine III. Penicillin prophylaxis IV. Thromboprophylaxis with low molecular weight heparin Select the correct answer using the code given below :

Hemoglobinopathies Indian Medical PG Practice Questions and MCQs

Question 1: The primary defect which leads to sickle cell anemia is:

A. An abnormality in porphyrin part of hemoglobin
B. A nonsense mutation in the β-chain of HbA
C. Substitution of valine by glutamate in the α-chain of HbA
D. Replacement of glutamate by valine in β-chain of HbA (Correct Answer)

Explanation: ***Replacement of glutamate by valine in β-chain of HbA*** - The primary defect in sickle cell anemia is a **point mutation** that leads to the replacement of **glutamic acid** with **valine** in the **sixth position** of the β-globin chain [1]. - This mutation causes the hemoglobin (HbS) to polymerize under low oxygen conditions, resulting in the characteristic **sickle-shaped red blood cells** [1]. *A nonsence mutation in the I3-chain of HbA* - A nonsense mutation leads to a **premature stop codon**, which is not the mechanism behind sickle cell anemia. - This mutation does not involve the β-globin chain, which is critical in this specific disorder. *Substitution of valine by glutamate in the a-chain of HbA* - This statement is incorrect as sickle cell anemia specifically involves the **β-chain**, not the **α-chain**. - Substituting valine with glutamate does not cause sickling but rather the opposite of the actual defect observed in this condition. *An abnormality in porphyrin part of hemoglobin* - Sickle cell anemia does not arise from **porphyrin metabolism issues**, which are related to conditions like **porphyrias**. - The primary defect is a change in the amino acid sequence, not in the porphyrin structure of hemoglobin. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 598-599.

Question 2: A child presents with recurrent chest infections and abdominal pain. There is a history of 1 blood transfusion in the past. On examination, he had icterus and mild splenomegaly. Electrophoresis shows increased HbA2, HbF, and S spike. What is the likely diagnosis?

A. HbC disease
B. Sickle cell disease
C. Aplastic anemia
D. Sickle Beta Thalassemia (Correct Answer)

Explanation: ***Sickle Beta Thalassemia*** - The combination of **sickle cell disease manifestations** (recurrent chest infections, abdominal pain, icterus, splenomegaly) with **electrophoresis showing increased HbA2, elevated HbF, and S spike** is diagnostic of **Sickle Beta Thalassemia**. - **Increased HbA2 (>3.5%)** is the key distinguishing feature that differentiates this from pure sickle cell disease. It indicates co-inheritance of a **beta-thalassemia gene** along with the **sickle cell gene**. - Clinical presentation is similar to sickle cell disease with **vaso-occlusive crises**, **acute chest syndrome**, hemolytic anemia, and organomegaly. - The severity depends on the type: S/β⁰-thalassemia (no HbA production) is clinically more severe and similar to SS disease, while S/β⁺-thalassemia (reduced HbA) tends to be milder. *Sickle cell disease* - Pure sickle cell disease (HbSS) presents with similar clinical features: recurrent chest infections, abdominal pain, hemolysis, and splenomegaly. - However, electrophoresis would show **normal or only slightly elevated HbA2 (2-3%)**, not the increased HbA2 mentioned in this case. - The presence of significantly increased HbA2 rules out pure sickle cell disease. *HbC disease* - Patients with HbC disease typically have **mild chronic hemolytic anemia** and **splenomegaly** but usually lack severe vaso-occlusive crises. - Electrophoresis would show primarily **HbC**, not an S spike. - The clinical picture is much milder than described in this case. *Aplastic anemia* - Characterized by **pancytopenia** due to bone marrow failure, leading to fatigue, infections, and bleeding tendency. - Does not involve hemolysis, icterus, or abnormal hemoglobin variants on electrophoresis. - The electrophoresis findings completely exclude this diagnosis.

Question 3: Which of the following has Autosomal Recessive inheritance?

A. Osteogenesis imperfecta
B. Hereditary spherocytosis
C. von Willebrand Disease Type 1
D. Sickle cell anaemia (Correct Answer)

Explanation: **Sickle cell anaemia** - This condition is inherited in an **autosomal recessive** pattern [2], meaning an individual must inherit two copies of the defective gene (one from each parent) to manifest the disease [3]. - It is caused by a mutation in the **beta-globin gene** [1], leading to abnormal hemoglobin production and characteristic sickle-shaped red blood cells [1]. *Osteogenesis imperfecta* - This disorder is predominantly inherited in an **autosomal dominant** pattern, meaning only one copy of the mutated gene is sufficient to cause the condition. - It is characterized by **brittle bones** due to defects in type I collagen synthesis. *Hereditary spherocytosis* - The most common and severe forms of hereditary spherocytosis are inherited as an **autosomal dominant** trait, though rarer autosomal recessive forms exist. - It involves defects in red blood cell membrane proteins, leading to **spherocytes** and hemolytic anemia. *von Willebrand Disease Type 1* - This is the most common type of von Willebrand disease and is inherited in an **autosomal dominant** pattern. - It is characterized by a **partial quantitative deficiency** of von Willebrand factor. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 598-599. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. (Basic Pathology) introduces the student to key general principles of pathology, both as a medical science and as a clinical activity with a vital role in patient care. Part 2 (Disease Mechanisms) provides fundamental knowledge about the cellular and molecular processes involved in diseases, providing the rationale for their treatment. Part 3 (Systematic Pathology) deals in detail with specific diseases, with emphasis on the clinically important aspects., pp. 53-54. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 150-151.

Question 4: A 22-year-old male with a known history of sickle cell disease presents with sudden onset chest pain, dyspnea, and cyanosis. What is the most likely diagnosis and the immediate treatment?

A. Diagnosis: Acute chest syndrome; Treatment: Provide oxygen and hydration (Correct Answer)
B. Diagnosis: Pulmonary embolism; Treatment: Start anticoagulation
C. Diagnosis: Asthma exacerbation; Treatment: Use bronchodilators
D. Diagnosis: Pneumonia; Treatment: Administer antibiotics

Explanation: Everything in the prompt remains as is, but with citations added: ***Diagnosis: Acute chest syndrome; Treatment: Provide oxygen and hydration*** - The sudden onset of chest pain, dyspnea, and cyanosis in a patient with **sickle cell disease** is highly indicative of **acute chest syndrome (ACS)**, a common and serious complication [1]. - Immediate management involves supportive care including **oxygen supplementation** to combat hypoxemia and **adequate hydration** to prevent further sickling and improve blood flow [1]. *Diagnosis: Pulmonary embolism; Treatment: Start anticoagulation* - While pulmonary embolism can cause similar symptoms, it is less likely to present with **cyanosis** as a primary feature in sickle cell disease compared to ACS. - Although anticoagulation is the treatment for PE, it is not the immediate priority for a patient with suspected ACS, where **oxygen** and **hydration** are crucial [1]. *Diagnosis: Asthma exacerbation; Treatment: Use bronchodilators* - Asthma exacerbation would be characterized by **wheezing** and a history of asthma, which are not mentioned in the patient's presentation. - While bronchodilators are the treatment for asthma, they would not address the underlying **sickling crisis** or its pulmonary manifestations [1]. *Diagnosis: Pneumonia; Treatment: Administer antibiotics* - Pneumonia can cause chest pain and dyspnea, but **cyanosis** suggests a more acute and severe oxygenation issue beyond typical pneumonia at onset. - Although antibiotics are the treatment for bacterial pneumonia, they are not the immediate first-line intervention if ACS is suspected, especially given the prompt needs for **oxygen** and **hydration** [1].

Question 5: Which of the following statements about hemoglobin is true?

A. Each hemoglobin molecule can bind up to six O2 molecules.
B. Each hemoglobin subunit contains two heme groups, which bind oxygen.
C. Hemoglobin consists of two alpha and two beta subunits, each capable of binding one O2 molecule. (Correct Answer)
D. Each hemoglobin molecule is made of 6 polypeptide chains.

Explanation: ***Hemoglobin consists of two alpha and two beta subunits, each capable of binding one O2 molecule.*** - A **hemoglobin molecule is a tetramer**, meaning it is composed of four protein subunits: two alpha (α) chains and two beta (β) chains. - Each of these four subunits contains one **heme group**, which is an iron-containing porphyrin complex that can reversibly bind one molecule of **oxygen (O2)**. *Each hemoglobin molecule can bind up to six O2 molecules.* - A single hemoglobin molecule, with its **four heme groups**, can bind a maximum of **four O2 molecules**, not six. - The capacity for oxygen binding is directly proportional to the number of heme groups present in the hemoglobin molecule. *Each hemoglobin subunit contains two heme groups, which bind oxygen.* - Each individual **hemoglobin subunit (alpha or beta)** contains **only one heme group**, not two. - Therefore, a complete hemoglobin molecule (with four subunits) contains a total of four heme groups. *Each hemoglobin molecule is made of 6 polypeptides, one for each subunit.* - A hemoglobin molecule is composed of **four polypeptide chains** (two alpha and two beta), not six. - This tetrameric structure is crucial for its function and **cooperative oxygen binding**.

Question 6: In sickle cell anemia, the mutation at codon 6 results in the substitution of which amino acid?

A. Valine for glutamic acid (Correct Answer)
B. Isoleucine for valine
C. Valine for isoleucine
D. Glutamic acid for valine

Explanation: ***Valine for glutamic acid*** - In **sickle cell anemia**, the normal **glutamic acid** at codon 6 of the $\beta$-globin chain is replaced by **valine**. - This single amino acid substitution is responsible for the abnormal **hemoglobin S (HbS)** and the characteristic sickling of red blood cells. *Isoleucine for valine* - This substitution is **not characteristic** of sickle cell anemia. - While other hemoglobinopathies exist, this specific change does not lead to the sickle cell phenotype. *Valine for isoleucine* - This substitution is **not the primary genetic defect** found in sickle cell anemia. - The mutation in sickle cell anemia involves the replacement of a negatively charged amino acid with a neutral one. *Glutamic acid for valine* - This represents the **reverse substitution** of what occurs in sickle cell anemia. - In sickle cell, valine replaces glutamic acid, not the other way around.

Question 7: A 25-year-old lady presented with anemia, jaundice, and recurrent joint pains. All of the following are true except:

A. HbA will be undetectable
B. She may have retinopathy
C. Hydroxyurea would help her
D. She can present with pulmonary bleeds (Correct Answer)

Explanation: ***She can present with pulmonary bleeds*** - The symptoms of **anemia**, **jaundice**, and recurrent **joint pains** in a 25-year-old suggest **sickle cell anemia**. Pulmonary bleeds are not a typical or common presentation of sickle cell disease; rather, patients are more prone to **acute chest syndrome**, which involves pulmonary infiltrates, but not usually frank bleeding [2]. - While various complications can affect the lungs in sickle cell disease, **pulmonary hemorrhage** is rare and not a characteristic feature. *HbA will be undetectable* - In **sickle cell anemia (Hb SS)**, the body exclusively produces **hemoglobin S (HbS)**, meaning **adult hemoglobin (HbA)**, the normal form, is indeed undetectable [3], [4]. - This is because the patient is homozygous for the **sickle gene**, preventing the synthesis of normal beta-globin chains [4]. *She may have retinopathy* - **Sickle cell retinopathy** is a common complication due to **vaso-occlusion** in the retinal vessels, leading to ischemia, neovascularization, and potentially vision loss. - This can manifest as various stages of proliferative retinopathy, often requiring treatment to preserve vision. *Hydroxyurea would help her* - **Hydroxyurea** is a medication used to reduce the frequency and severity of **sickle cell crises** and mitigate complications [1]. - It works by increasing the production of **fetal hemoglobin (HbF)**, which interferes with the polymerization of HbS and improves red blood cell function [1].

Question 8: Which of the following conditions is the classic example of acute intravascular hemolysis triggered by oxidative stress?

A. Hereditary spherocytosis
B. Sickle cell disease
C. Acute G6PD deficiency (Correct Answer)
D. None of the options

Explanation: ***b and c*** - Intravascular hemolysis is commonly associated with both **Acute G6PD deficiency** and **Hereditary spherocytosis**, leading to destruction of red blood cells in the bloodstream [1]. - These conditions are characterized by **high levels of hemoglobinuria** and **low haptoglobin**, indicative of intravascular hemolysis. *Sickle cell ds* - Sickle cell disease primarily causes **extravascular hemolysis** due to splenic sequestration rather than **intravascular** destruction [3]. - The clinical features include **vaso-occlusive crises** and splenic infarction rather than hemolysis within the blood vessels. *Acute G6PD* - While acute G6PD deficiency can lead to hemolysis, it is typically **triggered by oxidative stress** rather than occurring continuously [2]. - The hemolysis in G6PD deficiency occurs more in an **extravascular** manner unless acute stress occurs, which can result in **acute intravascular hemolysis, marked by anemia, hemoglobinemia, and hemoglobinuria** [4]. *Hereditary spherocytosis* - This condition primarily causes **extravascular hemolysis** through the spleen, where abnormal spherocytes are destroyed [1]. - Although it leads to anemia, the hallmark of hereditary spherocytosis is the **spleen's role** in hemocyte destruction rather than intravascular hemolysis.

Question 9: Which of the following are secondary iron overload conditions? I. Transfusion related iron load II. Thalassemia III. Hepatitis C associated liver disease Select the correct answer using the code given below :

A. I and II only
B. I and III only
C. II and III only
D. I, II and III (Correct Answer)

Explanation: ***I, II and III*** - All three listed conditions—**transfusion-related iron load**, **thalassemia**, and **Hepatitis C associated liver disease**—are well-recognized causes of secondary iron overload. - Secondary iron overload occurs due to external factors or underlying diseases that cause increased iron absorption or repeated administration of iron. [1] *I and II only* - This option is incomplete as **Hepatitis C associated liver disease** can also lead to secondary iron overload due to impaired iron metabolism and chronic inflammation. - It dismisses a known cause of secondary iron accumulation. *I and III only* - This option is incomplete because **thalassemia**, particularly **transfusion-dependent thalassemia**, is a classic example of secondary iron overload due to frequent blood transfusions and ineffective erythropoiesis. - It overlooks a major cause of transfusion-related iron accumulation. [1] *II and III only* - This option is incomplete as **transfusion-related iron load** is a direct and common cause of secondary iron overload, especially in patients requiring regular blood transfusions for conditions like anemia. [1] - It ignores the most direct mechanism of iron accumulation in many chronic diseases.

Question 10: Which of the following treatments are recommended for a pregnant woman suffering from sickle cell disease ? I. Folic acid 1 mg daily II. Azathioprine III. Penicillin prophylaxis IV. Thromboprophylaxis with low molecular weight heparin Select the correct answer using the code given below :

A. I, II and IV
B. I, III and IV (Correct Answer)
C. I, II and III
D. II, III and IV

Explanation: ***I, III and IV*** - **Folic acid 5 mg daily** (not 1mg) is essential in pregnancy, especially for women with **sickle cell disease**, to prevent **megaloblastic anemia** due to increased red cell turnover [1]. - **Penicillin prophylaxis** is crucial to prevent **Bacterial infections** as patients with sickle cell disease are at increased risk of infection, especially from encapsulated organisms, due to **functional asplenia** [1]. - **Thromboprophylaxis with low molecular weight heparin** is recommended because pregnancy in sickle cell disease significantly increases the risk of **venous thromboembolism** [1]. *I, II and IV* - **Azathioprine** is an immunosuppressant typically used for autoimmune conditions or organ transplantation, and it is **not a standard treatment** for managing sickle cell disease itself during pregnancy. - While folic acid and thromboprophylaxis are indicated, the inclusion of azathioprine makes this option incorrect. *I, II and III* - This option incorrectly includes **azathioprine**, an immunosuppressant not indicated for routine sickle cell management in pregnancy. - It also omits crucial **thromboprophylaxis**, which is vital given the increased risk of blood clots. *II, III and IV* - This option correctly includes **penicillin prophylaxis** and **thromboprophylaxis** but **incorrectly omits folic acid**, which is a cornerstone of daily management for all pregnant women with sickle cell disease. - It also incorrectly includes **azathioprine**, which is not a standard treatment.

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