Thalassemias — MCQs
A patient presents with elevated serum iron, low TIBC, and high ferritin. Which of the following conditions is most likely?
A female patient presented with fatigue and a history of piles. Routine complete blood count analysis showed hemoglobin of 9 g/dL, MCV 60fL, and RBC count of 5.2 million. A peripheral smear is provided. Which of the following is the next best investigation after the smear for this patient?
Diagnosis of beta thalassemia is established by what?
Which malformation is associated with mutations in the HOX gene?
Which condition is associated with defects in pre-mRNA splicing and SMN protein dysfunction?
A patient has MCV <80, MCH <23. Which type of anaemia shall be classified?
A 34-year-old, G1P0, presents for genetic counseling at 12 weeks' gestation. The patient has two sisters and a brother; her father has hemophilia. Her siblings are not affected, but she has a nephew who is affected. What is the inheritance pattern of this disorder?
The shown pattern in electrophoresis is due to:
A normal female, whose father is color blind, marries a normal man. What are the chances of their son being color blind?
Ferritin biosynthesis is regulated by the serum level of which substance?
Thalassemias Indian Medical PG Practice Questions and MCQs
Question 1: A patient presents with elevated serum iron, low TIBC, and high ferritin. Which of the following conditions is most likely?
- A. Lead poisoning
- B. Acute hepatitis
- C. Iron-deficiency anemia
- D. Hemochromatosis (Correct Answer)
Explanation: ***Hemochromatosis*** - **Hereditary hemochromatosis** is characterized by excessive iron absorption, leading to **iron overload** in tissues and organs [1][3]. - The classic lab findings include **elevated serum iron**, **elevated ferritin** (reflecting increased iron stores), and **low total iron-binding capacity (TIBC)** due to increased iron saturation of transferrin [1]. *Lead poisoning* - **Lead poisoning** can cause **microcytic anemia** due to inhibition of heme synthesis enzymes, but it does not typically present with elevated serum iron or ferritin. - It's more commonly associated with **basophilic stippling** on peripheral blood smear and **elevated lead levels** in the blood. *Acute hepatitis* - **Acute hepatitis** can cause an elevation in **ferritin** as an acute phase reactant due to inflammation and liver cell damage [1]. - However, it typically does not present with simultaneously **elevated serum iron** and **low TIBC** in the same pattern as hemochromatosis, and iron metabolism disorders are not its primary feature. *Iron-deficiency anemia* - **Iron-deficiency anemia** is characterized by **low serum iron**, **low ferritin** (reflecting depleted iron stores), and **elevated TIBC** as the body tries to maximize iron absorption [2]. - These findings are directly opposite to the laboratory values presented in the question [2].
Question 2: A female patient presented with fatigue and a history of piles. Routine complete blood count analysis showed hemoglobin of 9 g/dL, MCV 60fL, and RBC count of 5.2 million. A peripheral smear is provided. Which of the following is the next best investigation after the smear for this patient?
- A. HbA2 levels
- B. Serum ferritin levels (Correct Answer)
- C. Serum folate levels
- D. Serum homocysteine levels
Explanation: ***Serum ferritin levels*** - The **low hemoglobin** and **low MCV (microcytic anemia)** indicate a likely iron deficiency, commonly assessed by serum ferritin levels [1]. - The patient's **history of piles** suggests possible gastrointestinal bleeding, further pointing to the need for iron studies. *Serum folate levels* - Typically evaluated in cases of **macrocytic anemia**, which is not indicated here due to a **low MCV**. - Folate deficiency leads to larger, immature red cells, contrasting the findings of microcytic anemia in this patient. *Serum homocysteine levels* - While elevated levels can indicate **vitamin B12 or folate deficiency**, they are not specific for iron deficiency anemia. - The current presentation does not suggest deficiencies of B12 or folate, making this test less relevant. *HbA2 levels* - Useful in diagnosing **beta-thalassemia**, but not indicated in the context of evident **microcytic anemia** and fatigue without hemolysis or family history [1]. - The patient's profile does not align with thalassemia, thus making this investigation unnecessary. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 590-591.
Question 3: Diagnosis of beta thalassemia is established by what?
- A. Hb electrophoresis (Correct Answer)
- B. NESTROFT screening test
- C. Hemoglobin A1c test
- D. Presence of target cells in blood smear
Explanation: Hb electrophoresis - Hemoglobin electrophoresis directly measures the relative proportions of different hemoglobin types (HbA, HbA2, HbF), which is crucial for identifying the characteristic reduction in HbA and elevation of HbA2 and HbF in beta thalassemia. [1] - This method provides a definitive diagnostic profile by separating hemoglobin based on their electrical charge and size, allowing for quantification of abnormal hemoglobin variants. [1] *NESTROFT screening test* - The NESTROFT (Naked Eye Single Tube Red cell Osmotic Fragility Test) is a screening tool used to identify individuals with thalassemia traits and is not a definitive diagnostic test. - While useful for mass screening due to its simplicity and cost-effectiveness, it requires confirmation with more specific tests like hemoglobin electrophoresis. [1] *Hemoglobin A1c test* - The Hemoglobin A1c (HbA1c) test is primarily used to monitor long-term blood glucose control in individuals with diabetes. [2] - It measures the percentage of hemoglobin glycated over a period of 2-3 months and has no direct diagnostic utility for thalassemia. [2] *Presence of target cells in blood smear* - The presence of target cells in a blood smear is a non-specific finding that can be observed in various conditions, including iron deficiency anemia, liver disease, and other hemoglobinopathies, in addition to thalassemia. - While suggestive of a thalassemic disorder, it is not a conclusive diagnostic criterion and requires further investigation with specific diagnostic tests.
Question 4: Which malformation is associated with mutations in the HOX gene?
- A. Polysyndactyly (Correct Answer)
- B. Holoprosencephaly
- C. Mayer Rokitansky syndrome
- D. Gorlin syndrome
Explanation: ***Polysyndactyly*** - The **HOX gene** plays a critical role in limb development and is associated with the malformation of **polysyndactyly**, which is characterized by extra fingers or toes [1]. - This condition is due to the disruption of the normal **patterning** during limb formation, directly involving the action of HOX genes [1]. *Gorlin syndrome* - Gorlin syndrome is primarily caused by mutations in the **PTCH1 gene**, linked to **basal cell carcinoma** and other abnormalities. - It does not involve HOX gene mutations, hence is **not** related to limb malformations. *Holoprosencephaly* - Holoprosencephaly is a developmental condition often linked to **chromosomal anomalies** and abnormal embryonic development, **not specifically** HOX gene mutations. - It refers to the incomplete separation of the forebrain, distinct from the **limb malformations** associated with HOX genes. *Mayer Rokitansky syndrome* - Mayer-Rokitansky syndrome involves **agenesis** or **hypoplasia** of the uterus and upper two-thirds of the vagina, which is due to other genetic factors. - This condition is not related to the functions of the **HOX genes** in limb or skeletal development. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Bones, Joints, and Soft Tissue Tumors, p. 1186.
Question 5: Which condition is associated with defects in pre-mRNA splicing and SMN protein dysfunction?
- A. Sickle cell disease
- B. Huntington's disease
- C. Spinal muscular atrophy (Correct Answer)
- D. α-Thalassemia
Explanation: ***Spinal muscular atrophy*** - **Spinal muscular atrophy (SMA)** is primarily caused by mutations in the **SMN1 gene**, leading to insufficient production of the **survival motor neuron (SMN) protein**. - Without adequate SMN protein, defects occur in the **pre-mRNA splicing** of motor neuron genes, leading to the degeneration of **alpha motor neurons** in the spinal cord. *Sickle cell disease* - **Sickle cell disease** is an inherited **hemoglobinopathy** caused by a point mutation in the beta-globin gene, leading to the production of abnormal **hemoglobin S**. - This condition does not involve defects in pre-mRNA splicing or SMN protein dysfunction, but rather the **polymerization of hemoglobin S** under low oxygen conditions. *Huntington's disease* - **Huntington's disease** (formerly called Huntington chorea) is a neurodegenerative disorder caused by an **expanded CAG trinucleotide repeat** in the huntingtin gene. - Huntington's disease involves protein misfolding and aggregation, but not primary defects in pre-mRNA splicing or SMN protein dysfunction. *α-Thalassemia* - **α-Thalassemia** is a group of inherited blood disorders characterized by reduced or absent production of **alpha-globin chains**, typically due to **gene deletions** on chromosome 16. - This condition affects the assembly of hemoglobin and does not involve pre-mRNA splicing defects or SMN protein dysfunction.
Question 6: A patient has MCV <80, MCH <23. Which type of anaemia shall be classified?
- A. Microcytic hypochromic (Correct Answer)
- B. Normocytic normochromic
- C. Normocytic hypochromic
- D. Hyperchromic macrocytic
Explanation: ***Microcytic hypochromic*** - A **Mean Corpuscular Volume (MCV)** less than **80 fL** indicates **microcytosis** (small red blood cells) [1]. - A **Mean Corpuscular Hemoglobin (MCH)** less than **23 pg** indicates **hypochromia** (pale red blood cells due to reduced hemoglobin content) [1]. *Normocytic normochromic* - This classification refers to red blood cells with **normal MCV (80-100 fL)** and **normal MCH (27-32 pg)**. - Examples include anemia of chronic disease or acute blood loss, which do not fit the given lab values. *Normocytic hypochromic* - While **hypochromia (MCH <23)** is present, the **MCV is less than 80 fL**, which makes it microcytic, not normocytic. - This combination is not a standard classification; hypochromia typically accompanies microcytosis [1]. *Hyperchromic macrocytic* - **Macrocytic anemia** is characterized by an **MCV >100 fL**, which is the opposite of the given MCV of <80. - The term "hyperchromic" is generally not used for anemia classification because red blood cells have a maximal hemoglobin concentration and cannot be truly hyperchromic. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 590-591.
Question 7: A 34-year-old, G1P0, presents for genetic counseling at 12 weeks' gestation. The patient has two sisters and a brother; her father has hemophilia. Her siblings are not affected, but she has a nephew who is affected. What is the inheritance pattern of this disorder?
- A. X-linked inheritance (Correct Answer)
- B. Autosomal recessive
- C. Mitochondrial inheritance
- D. Multifactorial inheritance
Explanation: ***X-linked inheritance*** - Hemophilia is an **X-linked recessive disorder** - An affected father passes his X chromosome mutation to **all daughters**, making them **obligate carriers** (not affected but carry the gene) - The affected nephew (son of patient's sister) confirms the patient's sister is a carrier who passed the affected X chromosome to her son - Classic pattern: affected males, carrier females, skips generations through female carriers *Autosomal recessive* - Would require both parents to be carriers for offspring to be affected - An affected father would pass one mutant allele to all children, but this wouldn't make daughters obligate carriers unless mother also carried the gene - Pattern of father → carrier daughter → affected grandson is not typical of autosomal recessive inheritance *Mitochondrial inheritance* - Only transmitted from mother to **all children** regardless of gender - Affected father **cannot** pass mitochondrial disorders to offspring - Would show maternal transmission pattern with all children of affected mothers being affected *Multifactorial inheritance* - Involves combination of multiple genes and environmental factors - Does not follow clear Mendelian pattern - The distinct single-gene pattern (affected father, carrier daughters, affected male grandchild) indicates X-linked recessive, not multifactorial
Question 8: The shown pattern in electrophoresis is due to:
- A. Charges (Correct Answer)
- B. Molecular weight
- C. Bound oxygen
- D. Hydrophobicity
Explanation: ***Charges*** - Electrophoresis separates molecules, such as **hemoglobin variants**, based on their **electrical charge** when placed in an electric field. - Different amino acid substitutions in hemoglobin lead to changes in net charge, causing them to migrate at different rates in the gel, as seen by the distinct bands for Hb A, Hb S/D, and Hb A2. *Molecular weight* - While molecular weight can influence migration in some electrophoretic techniques (e.g., SDS-PAGE), standard hemoglobin electrophoresis primarily separates based on **charge differences**, not molecular size. - All common hemoglobin variants have a very similar **molecular weight** (approximately 64,500 Da), so this factor would not effectively separate them into distinct bands. *Bound oxygen* - The amount of **bound oxygen** to hemoglobin does not significantly alter its overall electrical charge or molecular weight to cause distinct bands in electrophoresis. - Oxygen binding is a dynamic process and does not account for the **structural differences** in hemoglobin variants that lead to their electrophoretic separation. *Hydrophobicity* - Hydrophobicity is a characteristic of molecules, but it is not the primary principle by which standard **gel electrophoresis** separates hemoglobin variants. - Techniques like **hydrophobic interaction chromatography** would exploit hydrophobicity, not the electrophoretic gel shown.
Question 9: A normal female, whose father is color blind, marries a normal man. What are the chances of their son being color blind?
- A. 25%
- B. 50% (Correct Answer)
- C. 75%
- D. No chance
Explanation: ***50%*** - The mother is a **carrier** because her father is colorblind, meaning she has one normal X chromosome and one affected X chromosome. - A son inherits his X chromosome from his mother; there is a **50% chance** that he will inherit the X chromosome carrying the colorblindness gene. *25%* - This percentage is typically associated with **autosomal recessive** inheritance patterns, not X-linked traits like colorblindness. - It would imply a different genetic setup for the parents than described, such as both parents being carriers for an autosomal recessive condition. *75%* - This probability would suggest a more complex genetic scenario or a condition with **incomplete penetrance** or a dominant inheritance pattern, which does not apply to X-linked recessive colorblindness in this context. - It does not align with the mendelian inheritance pattern for X-linked recessive traits when the mother is a carrier and the father is unaffected. *No chance* - This would only be true if the mother was **not a carrier** of the colorblindness gene. - Since her father was colorblind, she must have inherited his affected X chromosome, making her an obligate carrier.
Question 10: Ferritin biosynthesis is regulated by the serum level of which substance?
- A. Ceruloplasmin
- B. Hepcidin
- C. Iron (Correct Answer)
- D. Transferrin
Explanation: ### Explanation **Correct Option: C. Iron** Ferritin is the primary intracellular storage form of iron. Its biosynthesis is regulated at the **translational level** by the availability of free intracellular iron. This occurs via the **Iron Response Element (IRE)** and **Iron Regulatory Protein (IRP)** mechanism: * **Low Iron:** IRPs bind to the IRE located at the 5' untranslated region (UTR) of ferritin mRNA, physically blocking translation to prevent unnecessary storage. * **High Iron:** Iron binds to IRPs, causing them to dissociate from the mRNA. This allows the ribosome to translate the mRNA, increasing ferritin synthesis to safely sequester the excess iron. **Analysis of Incorrect Options:** * **A. Ceruloplasmin:** This is a copper-containing ferroxidase that converts Fe²⁺ to Fe³⁺ to facilitate iron binding to transferrin. It does not directly regulate ferritin synthesis. * **B. Hepcidin:** Known as the "Master Regulator of Iron Homeostasis," hepcidin controls systemic iron levels by degrading **ferroportin** (the iron exporter). While it influences iron availability, it does not directly regulate the biosynthesis of the ferritin protein. * **D. Transferrin:** This is the transport protein for iron in the plasma. While transferrin levels are inversely related to iron stores, it is a carrier, not a regulator of ferritin production. **High-Yield Clinical Pearls for NEET-PG:** * **Translational Control:** Ferritin is a classic example of post-transcriptional/translational regulation (unlike most proteins regulated at the transcriptional level). * **Serum Ferritin:** It is the **best initial test** and most sensitive marker for diagnosing **Iron Deficiency Anemia** (levels <15 ng/mL). * **Acute Phase Reactant:** Ferritin levels rise during inflammation, infection, or malignancy, which can mask an underlying iron deficiency. * **Hemosiderin:** This is an insoluble form of partially denatured ferritin, found in states of iron overload (e.g., Hemochromatosis).
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