Bone Marrow Failure Syndromes — MCQs
What is the best treatment option for a patient aged 65 years with severe aplastic anemia who has an HLA-compatible sibling available?
An 18-year-old male presents to the OPD with gum bleeding, fever, low total leukocyte count (TLC), and low platelet count. General examination is unremarkable. Further investigations reveal a low reticulocyte count, absent megakaryocytes, and no immature cells in the bone marrow. What is the most likely diagnosis?
Which disease will show the mode of inheritance depicted in this pedigree?
A 69-year-old woman, with poor dietary habits and alcoholism, is found to have a macrocytic anemia with hyper segmented neutrophils. Which of the following is the most appropriate diagnostic test?
Which of the following is not a characteristic of Fanconi's anemia?
False about Shwachman-Diamond syndrome
All are associated with malignancy except
Which of the following is not a chromosome breakage disorder?
The strongest occupational risk factor for hematological carcinoma is
Which of the following is most specific for congenital Rubella syndrome?
Bone Marrow Failure Syndromes Indian Medical PG Practice Questions and MCQs
Question 1: What is the best treatment option for a patient aged 65 years with severe aplastic anemia who has an HLA-compatible sibling available?
- A. Antithymocyte globulin followed by cyclosporine (Correct Answer)
- B. Non-myeloablative bone marrow transplantation from the HLA identical sibling
- C. Cyclosporine monotherapy
- D. Conventional myeloablative bone marrow transplantation from the HLA identical sibling
Explanation: Antithymocyte globulin followed by cyclosporine - For patients **over 50 years** with severe aplastic anemia and an HLA-compatible sibling, **immunosuppressive therapy** with antithymocyte globulin (ATG) and cyclosporine is generally preferred over transplantation due to increased transplant-related mortality risks in older individuals. [1] - This regimen aims to suppress the immune system's attack on hematopoietic stem cells, allowing for recovery of bone marrow function. *Non-myeloablative bone marrow transplantation from the HLA identical sibling* - While generally preferred for older patients with acute myeloid leukemia, **non-myeloablative transplantation** for severe aplastic anemia is often considered for those who fail initial immunosuppressive therapy, not as a first-line option. - The goal in aplastic anemia is to remove the autoimmune attack on stem cells and foster recovery, which immunosuppression can achieve with less toxicity in older patients. *Cyclosporine monotherapy* - **Cyclosporine monotherapy** is typically less effective than combination therapy with ATG for severe aplastic anemia. - Combination therapy provides a more robust immunosuppressive effect, leading to higher response rates. *Conventional myeloablative bone marrow transplantation from the HLA identical sibling* - **Conventional myeloablative transplantation** carries significant risks, including high treatment-related mortality, particularly in patients **over 50 years**. [1] - While it offers a potential cure, the risks in this age group are generally deemed too high as a first-line therapy compared to immunosuppression.
Question 2: An 18-year-old male presents to the OPD with gum bleeding, fever, low total leukocyte count (TLC), and low platelet count. General examination is unremarkable. Further investigations reveal a low reticulocyte count, absent megakaryocytes, and no immature cells in the bone marrow. What is the most likely diagnosis?
- A. Immune Thrombocytopenic Purpura (ITP)
- B. Myelodysplastic Syndrome (MDS)
- C. Aplastic anemia (Correct Answer)
- D. Acute Myeloid Leukemia (AML)
Explanation: ***Aplastic anemia*** - This condition is characterized by **pancytopenia** (low TLC and platelet count, implied low red blood cell count by low reticulocyte count) due to **bone marrow failure**. - The absence of **megakaryocytes** and other immature cells in the bone marrow confirms the **hypocellularity** typical of aplastic anemia. *Immune Thrombocytopenic Purpura (ITP)* - While ITP presents with **low platelet count** and potential gum bleeding [1], the bone marrow typically shows **normal or increased megakaryocytes**. - ITP does not explain the **low total leukocyte count** or low reticulocyte count seen in this patient [1]. *Myelodysplastic Syndrome (MDS)* - MDS involves **ineffective hematopoiesis** and can present with cytopenias, but the bone marrow is usually **hypercellular or normocellular** with dysplastic changes. - The absence of immature cells and overall hypoplasia does not fit the typical picture of MDS. *Acute Myeloid Leukemia (AML)* - AML is characterized by an overproduction of **immature myeloid cells (blasts)** [3], which are conspicuously absent in this patient's bone marrow description. - While AML can cause pancytopenia, the presence of **immature cells** in the bone marrow is its hallmark [3]. Gum hypertrophy is also a common clinical sign in AML [2].
Question 3: Which disease will show the mode of inheritance depicted in this pedigree?
- A. Achondroplasia (Correct Answer)
- B. Prader-Willi syndrome
- C. Wilson disease
- D. Wiskott-Aldrich syndrome
- E. Hemophilia A
Explanation: ***Achondroplasia*** - This pedigree shows an **autosomal dominant** inheritance pattern, characterized by affected individuals in every generation, affected offspring with at least one affected parent, and direct transmission from father to son (which **rules out X-linked**). Achondroplasia is an autosomal dominant disorder. - The presence of **affected individuals (shaded squares/circles)** in each successive generation and the 1:1 ratio of affected to unaffected offspring from affected parents mating with unaffected individuals supports autosomal dominant inheritance. *Prader-Willi syndrome* - This syndrome is caused by **genomic imprinting** or a chromosomal deletion on chromosome 15, typically inherited from the father. It does not follow a simple Mendelian dominant or recessive inheritance pattern. - While it has a genetic basis, its inheritance pattern is **complex** and involves specific parental origin of the genetic defect, unlike the clear autosomal dominant pattern shown. *Wilson disease* - Wilson disease is an **autosomal recessive** disorder, meaning affected individuals inherit two copies of the mutated gene (one from each parent). - This pedigree does not show skipped generations or unaffected parents having affected offspring, which would be characteristic of **autosomal recessive** inheritance. *Wiskott-Aldrich syndrome* - Wiskott-Aldrich syndrome is an **X-linked recessive** disorder. This means it primarily affects males, and affected fathers cannot pass the trait to their sons. - The pedigree shows **affected females** (shaded circles) and **father-to-son transmission** (e.g., father in second generation to son in third generation, assuming the leftmost branch is the paternal line), which rules out X-linked inheritance. *Hemophilia A* - Hemophilia A is an **X-linked recessive** disorder affecting the Factor VIII gene, predominantly affecting males. - Similar to Wiskott-Aldrich syndrome, the presence of **father-to-son transmission** in the pedigree rules out X-linked inheritance patterns, as affected fathers cannot pass X-linked traits to their sons.
Question 4: A 69-year-old woman, with poor dietary habits and alcoholism, is found to have a macrocytic anemia with hyper segmented neutrophils. Which of the following is the most appropriate diagnostic test?
- A. serum folate levels
- B. bone marrow
- C. RBC folate levels (Correct Answer)
- D. Schilling test
Explanation: RBC folate levels - **RBC folate levels** reflect **tissue folate stores** and are less susceptible to daily dietary fluctuations than serum folate. - This test is considered a more reliable indicator for diagnosing **chronic folate deficiency**, which is consistent with poor dietary habits and alcoholism. *serum folate levels* - **Serum folate levels** are easily influenced by recent dietary intake, making them less indicative of long-term folate stores [1]. - A normal serum folate level can be seen in patients with **tissue folate deficiency** if they have recently ingested folate-rich foods [1]. *bone marrow* - A **bone marrow biopsy** might show megaloblastic changes, but it is an invasive procedure and is usually reserved for cases where the diagnosis remains unclear after less invasive tests [2]. - While it can confirm **megaloblastic anemia**, it does not specifically differentiate between **folate** and **B12 deficiencies** as the primary diagnostic tool. *Schilling test* - The **Schilling test** is used to diagnose **vitamin B12 malabsorption** (pernicious anemia or other causes), not folate deficiency. - This patient's clinical picture points more towards a **folate deficiency** given the poor dietary habits and alcoholism, although B12 deficiency can also cause macrocytic anemia [3].
Question 5: Which of the following is not a characteristic of Fanconi's anemia?
- A. Skeletal anomalies
- B. Pancytopenia
- C. Chromosome fragility
- D. Bone marrow failure in infancy (Correct Answer)
Explanation: ***Bone marrow failure in infancy*** - Fanconi anemia patients are typically **asymptomatic at birth** with normal blood counts. - **Progressive bone marrow failure** develops gradually, with median age of onset around **7 years** (range 5-10 years). - While subtle hematologic changes (macrocytosis, elevated HbF) may appear earlier, clinically significant **pancytopenia does not occur in infancy**. - This delayed hematologic presentation distinguishes Fanconi anemia from other congenital bone marrow failure syndromes. *Pancytopenia* - **Pancytopenia** is the hallmark hematologic feature of Fanconi anemia, but develops in **mid-childhood**, not infancy. - Results from progressive bone marrow failure affecting all three cell lines: **red blood cells, white blood cells, and platelets**. - Thrombocytopenia is often the first manifestation, followed by anemia and neutropenia. *Skeletal anomalies* - **Skeletal anomalies** are common congenital malformations present in approximately **60-75%** of patients. - Include **radial ray defects** (absent or hypoplastic thumbs, absent radius), **short stature**, and other limb abnormalities. - These are present from birth and often lead to early clinical suspicion. *Chromosome fragility* - **Chromosome fragility** is the **diagnostic hallmark** of Fanconi anemia due to defective DNA repair mechanisms. - Diagnostic test uses **diepoxybutane (DEB)** or **mitomycin C (MMC)** to induce DNA crosslinks, revealing increased chromosomal breaks and rearrangements. - This test is positive regardless of age or hematologic status.
Question 6: False about Shwachman-Diamond syndrome
- A. Bone marrow dysfunction
- B. Exocrine pancreatic insufficiency
- C. Leucocytosis (Correct Answer)
- D. Short stature
Explanation: ***Leucocytosis*** - **Leucocytosis** (an increase in white blood cells) is generally **not** a feature of Shwachman-Diamond syndrome (SDS); rather, patients typically experience **neutropenia** (low neutrophils) due to bone marrow dysfunction. - This persistent or intermittent neutropenia is a hallmark of the immune deficiency seen in SDS, making leucocytosis an incorrect finding. *Bone marrow dysfunction* - **Bone marrow dysfunction** is a defining characteristic of Shwachman-Diamond syndrome, leading to various **cytopenias**, most notably **neutropenia**. - This dysfunction can also manifest as anemia or thrombocytopenia, contributing to the overall morbidity of the disease. *Exocrine pancreatic insufficiency* - **Exocrine pancreatic insufficiency** is a primary clinical feature of Shwachman-Diamond syndrome, leading to **malabsorption** and **failure to thrive**. - This insufficiency is due to abnormal pancreatic development and is distinct from the more severe pancreatic involvement seen in cystic fibrosis. *Short stature* - **Short stature** is a common finding in children with Shwachman-Diamond syndrome, often resulting from a combination of **growth plate abnormalities** and **malnutrition** due to pancreatic insufficiency. - It is considered a key **skeletal manifestation** of the disease, along with metaphyseal chondrodysplasia.
Question 7: All are associated with malignancy except
- A. Fragile - X syndrome (Correct Answer)
- B. Down's syndrome
- C. Fanconi's anaemia
- D. Bloom syndrome
Explanation: ***Fragile - X syndrome*** - While Fragile-X syndrome is a common cause of **inherited intellectual disability**, it is **not directly associated with an increased risk of malignancy**. - Its pathology involves a mutation in the **FMR1 gene**, leading to an altered protein required for normal neuronal development, rather than a predisposition to cancer. *Down's syndrome* - Individuals with Down's syndrome have a **significantly increased risk of developing certain malignancies**, most notably **acute lymphoblastic leukemia (ALL)**. - The abnormal chromosome 21 dosage is thought to disrupt normal cell growth and differentiation, predisposing to cancer. *Fanconi's anaemia* - Fanconi's anaemia is a **genetic disorder characterized by bone marrow failure** and a **high predisposition to various cancers**, particularly **acute myeloid leukemia (AML)** and solid tumors. - It involves defects in **DNA repair pathways**, leading to genomic instability and increased oncogenic mutations. *Bloom syndrome* - Bloom syndrome is a rare genetic disorder characterized by **growth deficiency**, a **photosensitive rash**, and a **markedly increased risk of developing various cancers** at an early age. - It is caused by a mutation in the **BLM gene**, which plays a crucial role in maintaining genomic stability and DNA repair.
Question 8: Which of the following is not a chromosome breakage disorder?
- A. Bloom syndrome
- B. Ataxia telangiectasia
- C. Duchenne muscular dystrophy (Correct Answer)
- D. Fanconi anemia
Explanation: ***Duchenne muscular dystrophy*** - Duchenne muscular dystrophy is primarily a **muscle degeneration disorder** caused by mutations in the **dystrophin gene**, not a chromosome breakage disorder. - It does not involve issues with **chromosomal stability** or breakage, unlike the others listed. *Ataxia telangiectasia* - Ataxia telangiectasia is associated with defects in **DNA repair mechanisms**, leading to **chromosome breakage** and instability [1]. - Patients exhibit progressive **ataxia**, **telangiectasia**, and increased sensitivity to radiation. *Fanconi anemia* - Fanconi anemia is characterized by a defect in the **DNA repair pathway**, resulting in increased **chromosome breakage** [1]. - It is associated with **bone marrow failure** and development of various malignancies. *Bloom syndrome* - Bloom syndrome results from defects in the **BLM gene**, leading to **genomic instability** and an increased rate of chromosome breakage [1]. - This condition causes symptoms like **short stature**, **facial lesions**, and a predisposition to cancer. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 322-323.
Question 9: The strongest occupational risk factor for hematological carcinoma is
- A. Benzene (Correct Answer)
- B. Lithium
- C. Radiation exposure
- D. Cigarette smoke
Explanation: ***Benzene*** - Benzene exposure is recognized as a potent **carcinogen** linked to various hematological malignancies, including **leukemia** [1]. - It affects the **bone marrow**, leading to dysplastic changes and ultimately malignancy. *Nicotine* - Although nicotine is associated with **smoking-related cancers**, it is not directly linked to **hematological carcinomas**. - Its primary role is in causing **lung cancer**, rather than blood cancers. *Lithium* - Lithium is primarily used for **bipolar disorder** and does not have a known link to causing hematological malignancies. - Side effects are more related to **nephrotoxicity** rather than carcinogenic effects. *Alcohol* - Alcohol consumption is primarily associated with **liver cancers** and not specifically linked to hematological carcinomas [2]. - It can contribute to general malignancy development but is not a direct cause of blood cancers. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, p. 286. [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. 217-218.
Question 10: Which of the following is most specific for congenital Rubella syndrome?
- A. Blueberry muffin rash is seen
- B. Triad of CRS are cataract, cardiac defects, sensorineural deafness (Correct Answer)
- C. Infection is most serious in the first trimester of pregnancy
- D. Virus can be isolated up to 12 months after birth
Explanation: ***Triad of CRS are cataract, cardiac defects, sensorineural deafness*** - The **classic Gregg triad** of **cataracts**, **cardiac defects** (especially patent ductus arteriosus and pulmonary artery stenosis), and **sensorineural deafness** is the **most specific and pathognomonic** feature of **congenital Rubella syndrome**. - While individual components can occur in other conditions, the **combination of this triad** is highly specific for CRS and distinguishes it from other congenital infections. - This triad was first described by **Norman Gregg** in 1941 and remains the hallmark diagnostic feature of congenital rubella syndrome. *Blueberry muffin rash is seen* - The **blueberry muffin rash** (dermal erythropoiesis) presents as purpuric lesions or small dark blue papules and can be seen in congenital rubella syndrome. - However, this finding is **NOT specific to rubella** and occurs in multiple congenital infections including **CMV, toxoplasmosis, parvovirus B19**, and can also be seen in neonatal malignancies like neuroblastoma. - While characteristic, it is less specific than the Gregg triad for diagnosing CRS. *Infection is most serious in the first trimester of pregnancy* - Maternal rubella infection during the **first trimester** carries the highest risk (up to 85% if infected before 12 weeks) of severe multi-organ abnormalities due to rapid organogenesis. - While true, this describes the **timing and severity** of infection rather than a specific clinical feature that distinguishes rubella from other congenital infections. - Many congenital infections (CMV, toxoplasmosis, HSV) are also more severe when acquired in early pregnancy. *Virus can be isolated up to 12 months after birth* - Infants with **congenital Rubella syndrome** can shed virus in bodily fluids (urine, nasopharyngeal secretions) for **12 months or longer** after birth. - This prolonged viral shedding is important for **infection control** and isolation precautions but is a virological characteristic rather than a specific diagnostic clinical feature. - Other congenital infections (CMV) can also demonstrate prolonged viral shedding in infants.
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