Lysosomal Storage Diseases — MCQs
In a patient presented with a fever and a positive filarial antigen test, what is the next appropriate method of management?
Tay-Sachs disease is due to a deficiency of which enzyme?
A child presents with bone pain and hepatosplenomegaly, indicative of Gaucher's disease. A trephine biopsy and aspirate show the following finding. Which of the following is the most likely enzyme deficient in this condition?
Enzyme replacement therapy is available for which of the following lysosomal storage disorders?
The uronic acid level in urine is elevated in what condition?
Glycogen storage disorders are primarily classified under which type of disorders?
Which of the following statements about Niemann-Pick disease is false?
Which enzyme deficiency causes Niemann-Pick disease, leading to lysosomal dysfunction?
Maroteaux-Lamy syndrome is characterized by deficiency of
Which of the following are metabolic causes of splenic enlargement?
Lysosomal Storage Diseases Indian Medical PG Practice Questions and MCQs
Question 1: In a patient presented with a fever and a positive filarial antigen test, what is the next appropriate method of management?
- A. Bone marrow biopsy
- B. DEC provocation test
- C. Detection of microfilariae in the blood smear (Correct Answer)
- D. Ultrasound of the scrotum
Explanation: ***Detection of microfilariae in the blood smear*** - A positive **filarial antigen test** indicates the presence of adult worms, and the next step is to confirm active infection by identifying **microfilariae**. [1] - **Nocturnal blood samples** are crucial because microfilariae of *Wuchereria bancrofti* and *Brugia malayi* exhibit **nocturnal periodicity**, meaning they are most abundant in peripheral blood between 10 PM and 2 AM. [1] *Bone marrow biopsy* - This procedure is typically used to diagnose **hematological disorders**, such as leukemia or lymphoma, or investigate causes of unexplained fever, but it is not indicated for filariasis. - While filariasis can rarely lead to **eosinophilia**, a bone marrow biopsy is not a diagnostic tool for filarial infection itself. *DEC provocation test* - The **diethylcarbamazine (DEC) provocation test** is used to bring out microfilariae into the peripheral blood during the daytime for species that exhibit nocturnal periodicity. [1] - However, it carries a risk of severe adverse reactions due to rapid killing of microfilariae, especially in cases of heavy infection, and is generally avoided when antigen tests are positive. [1] *Ultrasound of the scrotum* - Scrotal ultrasound can detect the characteristic "filarial dance sign" (motile adult worms) in the **lymphatic vessels of the scrotum and epididymis**, confirming lymphatic filariasis. [2] - While useful for assessing advanced disease manifestations like **hydrocele**, it does not quantify microfilaremia or replace the need for microscopic confirmation of circulating microfilariae to guide treatment.
Question 2: Tay-Sachs disease is due to a deficiency of which enzyme?
- A. Hexosaminidase B
- B. α-galactosidase
- C. Hexosaminidase A (Correct Answer)
- D. Sphingomyelinase
Explanation: ***Hexosaminidase A*** - **Tay-Sachs disease** is caused by a genetic deficiency in the lysosomal enzyme **hexosaminidase A (HexA)**. - This deficiency leads to the accumulation of **GM2 ganglioside** in neuronal cells, particularly in the brain, causing progressive neurodegeneration. *Hexosaminidase B* - A deficiency in **hexosaminidase B** is associated with **Sandhoff disease**, a lysosomal storage disorder similar to Tay-Sachs but typically more severe. - While HexA is composed of alpha and beta subunits, a deficiency specifically in the beta subunit is characteristic of Sandhoff disease. *α-galactosidase* - A deficiency in **α-galactosidase** is responsible for **Fabry disease**, an X-linked lysosomal storage disorder. - It leads to the accumulation of **globotriaosylceramide (Gb3)**, primarily affecting the kidneys, heart, and nervous system, and does not present with the neurological symptoms of Tay-Sachs. *Sphingomyelinase* - A deficiency in **sphingomyelinase** causes **Niemann-Pick disease (Type A and B)**, another lysosomal storage disorder. - This leads to the accumulation of **sphingomyelin** in various organs, resulting in hepatosplenomegaly, neurodegeneration (in Type A), and lung disease, distinct from Tay-Sachs.
Question 3: A child presents with bone pain and hepatosplenomegaly, indicative of Gaucher's disease. A trephine biopsy and aspirate show the following finding. Which of the following is the most likely enzyme deficient in this condition?
- A. Hexosaminidase
- B. Glucocerebrosidase (Correct Answer)
- C. Sphingomyelinase
- D. Alpha 1,4-glucosidase
Explanation: ***Correct: Glucocerebrosidase*** - The clinical presentation of **bone pain**, **hepatosplenomegaly**, and the characteristic histological finding of **lipid-laden macrophages** (Gaucher cells) with a **crinkled paper** appearance in the bone marrow aspirate are highly suggestive of **Gaucher's disease**. - **Gaucher's disease** is caused by a deficiency of the lysosomal enzyme **glucocerebrosidase**, leading to the accumulation of **glucocerebroside**. *Incorrect: Hexosaminidase* - Deficiency of **hexosaminidase A** is associated with **Tay-Sachs disease**, which presents with neurological degeneration but typically **lacks hepatosplenomegaly** and bone pain. - The histological findings in Tay-Sachs disease would show neuronal storage of **GM2 gangliosides**, not Gaucher cells. *Incorrect: Sphingomyelinase* - Deficiency of **sphingomyelinase** causes **Niemann-Pick disease**, characterized by hepatosplenomegaly, neurological involvement, and interstitial lung disease, but the storage cells (foam cells) have a **foamy appearance** due to sphingomyelin accumulation, not the "crinkled paper" appearance of Gaucher cells. - While there is organomegaly, the distinct **histological features** in the image rule out Niemann-Pick disease. *Incorrect: Alpha 1,4-glucosidase* - Deficiency of **alpha 1,4-glucosidase** (acid maltase) causes **Pompe disease** (Glycogen Storage Disease Type II), which primarily affects muscle and liver with **glycogen accumulation**. - Pompe disease does not typically present with the same type of **bone pain** or the characteristic **Gaucher cells** seen in the image.
Question 4: Enzyme replacement therapy is available for which of the following lysosomal storage disorders?
- A. Gaucher's disease (Correct Answer)
- B. Tay-Sachs disease
- C. None of the above
- D. Niemann-Pick disease Type C
Explanation: ***Gaucher's disease*** - Enzyme replacement therapy (ERT) with **imiglucerase**, **velaglucerase alfa**, or **taliglucerase alfa** is a highly effective treatment for Type 1 and Type 3 Gaucher's disease - It provides the deficient enzyme **glucocerebrosidase** (β-glucosidase), which breaks down glucocerebroside, preventing its accumulation in macrophages - ERT significantly reduces hepatosplenomegaly, improves bone disease, and corrects cytopenias *Niemann-Pick disease Type C* - **No enzyme replacement therapy** is currently available for Niemann-Pick disease Type C - This disorder involves defective cholesterol trafficking, not a single enzyme deficiency amenable to replacement - Treatment is primarily **supportive** with miglustat for neurological symptoms in some cases *Tay-Sachs disease* - There is currently **no effective enzyme replacement therapy** for Tay-Sachs disease - The deficient enzyme **hexosaminidase A** cannot effectively cross the **blood-brain barrier** to reach affected neurons in the CNS - Treatment is purely **supportive and palliative** *None of the above* - This option is incorrect because **Gaucher's disease** has well-established and FDA-approved enzyme replacement therapy
Question 5: The uronic acid level in urine is elevated in what condition?
- A. Tyrosinosis
- B. Maple syrup urine disease
- C. Mucopolysaccharidosis (Correct Answer)
- D. Niemann-Pick disease
Explanation: ***Mucopolysaccharidosis*** - **Mucopolysaccharidoses (MPS)** are a group of genetic disorders caused by the deficiency of lysosomal enzymes responsible for breaking down **glycosaminoglycans (GAGs)**, which are also known as mucopolysaccharides. - The accumulation of these undegraded GAGs, which contain **uronic acids**, leads to their excretion in the urine, hence the elevated uronic acid levels. *Tyrosinosis* - **Tyrosinosis (Tyrosinemia)** is a metabolic disorder characterized by the inability to properly break down the amino acid **tyrosine**. - It leads to the accumulation of *tyrosine* and its derivatives, not uronic acids, in the body fluids. *Maple syrup urine disease* - **Maple syrup urine disease (MSUD)** is an autosomal recessive metabolic disorder affecting the metabolism of branched-chain amino acids (BCAAs): **leucine, isoleucine, and valine**. - The disease is characterized by a distinctive sweet smell in the urine, reminiscent of maple syrup, due to the accumulation of these amino acids and their ketoacid derivatives, not uronic acids. *Niemann-Pick disease* - **Niemann-Pick disease** is a group of rare, inherited metabolic disorders that affect the body's ability to metabolize fats (**lipids**) within cells. - It results from a deficiency of an enzyme called acid sphingomyelinase or a defect in intracellular cholesterol trafficking, leading to the accumulation of sphingomyelin and cholesterol in various organs.
Question 6: Glycogen storage disorders are primarily classified under which type of disorders?
- A. Endocrine disorders
- B. Metabolic disorders (Correct Answer)
- C. Genetic disorders
- D. Lysosomal storage disorders
Explanation: ***Metabolic disorders*** - Glycogen storage disorders involve defects in the enzymes responsible for **glycogen synthesis** or degradation. - These enzymatic defects lead to abnormal accumulation or breakdown of **glycogen**, thus affecting cellular metabolism. *Genetic disorders* - While glycogen storage disorders are **inherited** and thus genetic, their primary classification focuses on the **metabolic pathways** affected. - This category is too broad and refers to the origin, not the specific functional impairment. *Lysosomal storage disorders* - These disorders involve defective lysosomal enzymes leading to the accumulation of various **substrates within lysosomes**. - Glycogen storage disorders primarily involve enzymes in the **cytoplasm** (or sometimes lysosomes for Pompe disease, but the general classification is metabolic). *Endocrine disorders* - Endocrine disorders involve dysfunction of **hormone production** or regulation. - Glycogen storage diseases are disorders of **carbohydrate metabolism** and do not directly involve hormonal imbalance as their primary pathology.
Question 7: Which of the following statements about Niemann-Pick disease is false?
- A. Due to deficiency of sphingomyelinase.
- B. CNS symptoms are present in type A.
- C. Type B Niemann-Pick disease is characterized by severe neurological symptoms. (Correct Answer)
- D. Histiocytes show PAS positive inclusions, and Type A is more severe.
Explanation: ***Type B Niemann-Pick disease is characterized by severe neurological symptoms.*** - This statement is **false** because **Type B Niemann-Pick disease** generally presents with **visceral involvement** (e.g., hepatosplenomegaly, lung disease) with **minimal to no neurological symptoms**. - **Severe neurological symptoms** are characteristic of **Type A Niemann-Pick disease**, which involves widespread CNS degeneration and a more rapidly progressive course. *Due to deficiency of sphingomyelinase.* - This statement is **true**. - Niemann-Pick disease (Types A and B) is caused by a deficiency of the enzyme **acid sphingomyelinase**, leading to the accumulation of sphingomyelin within lysosomes, particularly in macrophages. *CNS symptoms are present in type A.* - This statement is **true**. - **Type A Niemann-Pick disease** is the most severe form and is characterized by significant **neurodegeneration** in addition to visceral involvement. - Patients typically present with **developmental regression**, **ataxia**, and **spasticity** due to extensive sphingomyelin deposition in the central nervous system. *Histiocytes show PAS positive inclusions, and Type A is more severe.* - This statement is **true**. - The characteristic "foam cells" (lipid-laden macrophages/histiocytes) found in tissues of Niemann-Pick patients stain positive with **periodic acid–Schiff (PAS)** due to accumulated sphingomyelin. - **Type A Niemann-Pick disease** is indeed the most severe form, with a rapidly progressive course and early fatality, usually by early childhood.
Question 8: Which enzyme deficiency causes Niemann-Pick disease, leading to lysosomal dysfunction?
- A. Ceramidase
- B. Phospholipase C
- C. Beta-galactosidase
- D. Sphingomyelinase (Correct Answer)
Explanation: ***Sphingomyelinase*** - Niemann-Pick disease types A and B are caused by a deficiency in the enzyme **acid sphingomyelinase**, which is responsible for the breakdown of **sphingomyelin**. - This deficiency leads to the accumulation of **sphingomyelin** within lysosomes of various tissues, particularly in the brain, spleen, liver, and lungs. *Ceramidase* - A deficiency in **ceramidase** causes Farber disease, a rare lysosomal storage disorder characterized by joint deformities, subcutaneous nodules, and hoarseness. - While both ceramidase and sphingomyelinase are involved in **sphingolipid metabolism**, their specific substrates and the resulting clinical pathologies differ. *Phospholipase C* - **Phospholipase C** plays a crucial role in signal transduction by cleaving phospholipids, but its deficiency is not directly linked to Niemann-Pick disease. - Deficiencies in phospholipase C activity are associated with various cellular dysfunctions but not lysosomal storage disorders like Niemann-Pick. *Beta-galactosidase* - A deficiency in **beta-galactosidase** causes GM1 gangliosidosis and Morquio syndrome type B, both of which are lysosomal storage disorders. - These conditions involve the accumulation of specific **glycosphingolipids** or **keratan sulfate**, rather than sphingomyelin.
Question 9: Maroteaux-Lamy syndrome is characterized by deficiency of
- A. Arylsulfatase B (Correct Answer)
- B. Beta Glucuronidase
- C. Iduronate sulfatase
- D. Beta Galactosidase
Explanation: ***Arylsulfatase B*** - **Maroteaux-Lamy syndrome (MPS VI)** is caused by a deficiency of the enzyme **arylsulfatase B (ARSB)**, also known as N-acetylgalactosamine-4-sulfatase. - This enzyme deficiency leads to the accumulation of **dermatan sulfate** within lysosomes. *Beta Glucuronidase* - Deficiency of **beta-glucuronidase** is associated with **Sly syndrome (MPS VII)**, which has a distinct clinical presentation. - This enzyme is responsible for the degradation of **dermatan sulfate** and **heparan sulfate**. *Iduronate sulfatase* - Deficiency of **iduronate sulfatase** causes **Hunter syndrome (MPS II)**, leading to accumulation of heparan sulfate and dermatan sulfate. - Hunter syndrome has X-linked inheritance, distinguishing it from Maroteaux-Lamy syndrome. *Beta Galactosidase* - Deficiency of **beta-galactosidase** is responsible for **GM1 gangliosidosis** and **Morquio syndrome type B (MPS IVB)**. - These conditions have different clinical features and biochemical abnormalities compared to Maroteaux-Lamy syndrome.
Question 10: Which of the following are metabolic causes of splenic enlargement?
- A. Porphyria and Felty's syndrome
- B. Amyloid and Gaucher's disease (Correct Answer)
- C. Myelofibrosis and Weil's disease
- D. Rickets and Still's disease
Explanation: ***Amyloid and Gaucher's disease*** - **Amyloidosis** is characterized by the extracellular deposition of insoluble abnormal **fibrillar proteins (amyloid)** in various organs, including the spleen, leading to its enlargement [2]. - **Gaucher's disease** is a **lysosomal storage disorder** where macrophages accumulate **glucocerebroside**, particularly in the spleen, liver, and bone marrow, causing significant **splenomegaly** [1]. *Porphyria and Felty's syndrome* - **Porphyria** is a group of metabolic disorders primarily affecting **heme synthesis**, leading to diverse symptoms, but **splenomegaly** is not a primary or prominent feature. - **Felty's syndrome** is a severe manifestation of **rheumatoid arthritis** combined with **splenomegaly** and **neutrogenia**, and while it causes splenomegaly, it's an **immune-mediated** condition rather than a primary metabolic storage disease. *Myelofibrosis and Weil's disease* - **Myelofibrosis** is a **myeloproliferative neoplasm** characterized by bone marrow fibrosis, extramedullary hematopoiesis (often in the spleen), and **splenomegaly**, but it is not a metabolic disorder [3]. - **Weil's disease** is a severe form of **leptospirosis**, an **infectious disease** that can cause hepatosplenomegaly, but it is not a metabolic cause. *Rickets and Still's disease* - **Rickets** is a bone disease caused by a **vitamin D deficiency** leading to impaired bone mineralization, and it does not typically cause **splenomegaly**. - **Still's disease** (Systemic Juvenile Idiopathic Arthritis in children, or Adult-Onset Still's Disease) is an **inflammatory disorder** characterized by fever, rash, joint pain, and can cause **splenomegaly** as part of a systemic inflammatory response, not due to a metabolic storage issue. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 162-163. [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. 135-136. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of White Blood Cells, Lymph Nodes, Spleen, and Thymus, pp. 631-632.
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