Glycogen Storage Diseases — MCQs
Which glycogen storage disease does not affect muscles?
A 22-year-old athlete has episodes of rhabdomyolysis after intense exercise. Which metabolic disorder should be suspected?
Muscle phosphorylase deficiency leads to which glycogen storage disorder?
In an infant presenting with doll-like facies, which enzyme is deficient in Von Gierke disease?
An adolescent male patient came with pain in calf muscles on exercise. On biopsy excessive amount of glycogen was found to be present in the muscle. What is the most likely enzyme deficiency?
Glycogen synthase is activated by?
A person after consuming raw eggs presents with weakness, fatigue & hypoglycemia. Doctor gave him biotin supplements. Which biotin-dependent enzyme's reduced activity is most likely causing hypoglycemia in this patient:
Which of the following is a direct cause of ketosis in a patient with Von Gierke's disease?
Cardiomyopathy may be seen in all of the following conditions except.
Muscles cannot release free glucose from glycogen stores because of a deficiency of:
Glycogen Storage Diseases Indian Medical PG Practice Questions and MCQs
Question 1: Which glycogen storage disease does not affect muscles?
- A. Type 4 (Andersen disease)
- B. Type 2 (Pompe disease)
- C. Type 1 (Von Gierke disease) (Correct Answer)
- D. Type 3 (Cori disease)
Explanation: ***Type 1 (Von Gierke disease)*** - This is caused by a deficiency in **glucose-6-phosphatase**, an enzyme found primarily in the **liver** and **kidneys** but **NOT in muscle tissue**. - Since muscles do not express glucose-6-phosphatase and rely on glycogen phosphorylase for energy mobilization, this disease **does not affect muscle function**. - Clinical features include severe **hypoglycemia**, **lactic acidosis**, **hepatomegaly**, and **growth retardation**, but patients have **normal muscle strength and function**. *Type 2 (Pompe disease)* - Also known as **acid maltase deficiency**, this disease severely affects **all muscle types** including cardiac, skeletal, and smooth muscles. - It is a **lysosomal storage disease** causing progressive **muscle weakness**, **cardiomyopathy**, and **respiratory failure**. - This is the most significant muscle-affecting GSD. *Type 3 (Cori disease)* - Caused by **debranching enzyme (amylo-1,6-glucosidase) deficiency**, affecting both **liver and muscles**. - Patients develop **hepatomegaly**, **hypoglycemia**, and progressive **myopathy** with muscle weakness. - Muscle involvement is common and clinically significant. *Type 4 (Andersen disease)* - Due to **branching enzyme deficiency**, primarily causing **liver cirrhosis** and **hepatosplenomegaly**. - While mainly hepatic, this disease **can involve muscles** causing hypotonia and muscle weakness in some patients. - The abnormal, unbranched glycogen ("amylopectin-like") accumulates in multiple tissues including muscle.
Question 2: A 22-year-old athlete has episodes of rhabdomyolysis after intense exercise. Which metabolic disorder should be suspected?
- A. Pompe disease
- B. Cori disease
- C. Von Gierke disease
- D. McArdle disease (Correct Answer)
Explanation: ***McArdle disease*** - This condition, also known as **glycogen storage disease type V**, is caused by a deficiency in **myophosphorylase** (muscle glycogen phosphorylase). - This enzyme defect prevents the breakdown of **glycogen in muscle** during exercise, leading to energy depletion, muscle pain, cramps, and **rhabdomyolysis**. *Pompe disease* - Caused by a deficiency in **lysosomal α-1,4-glucosidase** (acid maltase), leading to glycogen accumulation in lysosomes. - Presents with a wide range of symptoms including **cardiomyopathy**, hypotonia (in infants), and respiratory problems, but less commonly exercise-induced rhabdomyolysis in adults. *Cori disease* - Also known as glycogen storage disease type III, characterized by a deficiency in **glycogen debranching enzyme**. - Mainly affects the **liver and muscles**, causing hepatomegaly, hypoglycemia, and muscle weakness, but exercise-induced rhabdomyolysis is not its primary presentation. *Von Gierke disease* - This is **glycogen storage disease type I**, caused by a deficiency in **glucose-6-phosphatase**. - Primarily affects the **liver and kidneys**, leading to severe fasting hypoglycemia, hepatomegaly, lactic acidosis, and hyperlipidemia, but not typically rhabdomyolysis.
Question 3: Muscle phosphorylase deficiency leads to which glycogen storage disorder?
- A. Hers disease
- B. Cori's disease
- C. Andersen disease
- D. McArdle's disease (Correct Answer)
Explanation: **McArdle's disease** - **McArdle's disease** (Glycogen Storage Disease Type V) is characterized by a deficiency of **muscle phosphorylase** (myophosphorylase). - This enzyme defect prevents the breakdown of glycogen in muscle cells, leading to symptoms like **exercise intolerance**, muscle pain, and cramping. *Hers disease* - **Hers disease** (Glycogen Storage Disease Type VI) is caused by a deficiency of **liver phosphorylase**. - Its primary manifestations are **hepatomegaly**, hypoglycemia, and sometimes hyperlipidemia, due to impaired glycogenolysis in the liver. *Cori's disease* - **Cori's disease** (Glycogen Storage Disease Type III) is caused by a deficiency of **glycogen debranching enzyme** (amylo-1,6-glucosidase). - This leads to abnormal glycogen structure accumulation in the liver, heart, and muscle, causing **hypoglycemia**, hepatomegaly, and myopathy. *Andersen disease* - **Andersen disease** (Glycogen Storage Disease Type IV) is caused by a deficiency of **glycogen branching enzyme** (amylo-α-1,4-α-1,6-transglucosidase). - This results in the formation of abnormally structured, long-chain glycogen, primarily affecting **liver** and sometimes heart, leading to cirrhosis and liver failure.
Question 4: In an infant presenting with doll-like facies, which enzyme is deficient in Von Gierke disease?
- A. Fructose 1,6 bisphosphatase
- B. Debranching enzyme
- C. Glucose 6 phosphatase (Correct Answer)
- D. Phosphorylase
Explanation: ***Glucose 6 phosphatase*** - **Von Gierke disease (Type I glycogen storage disease)** is characterized by a deficiency of **glucose-6-phosphatase**, an enzyme crucial for the final step of gluconeogenesis and glycogenolysis. - This enzyme's deficiency leads to the inability to release free glucose from the liver and kidneys, resulting in **hypoglycemia**, hepatomegaly, and the characteristic **doll-like facies** due to fat deposits. *Fructose 1,6 bisphosphatase* - This enzyme is involved in **gluconeogenesis**, catalyzing the conversion of fructose-1,6-bisphosphate to fructose-6-phosphate. - **Fructose-1,6-bisphosphatase deficiency** is a distinct metabolic disorder causing hypoglycemia, lactic acidosis, and hepatomegaly, but it does not present with the characteristic features of Von Gierke disease. *Debranching enzyme* - A deficiency in the **debranching enzyme** (**amylo-1,6-glucosidase**) is characteristic of **Cori's disease (GSD III)**. - While it also causes hepatomegaly and hypoglycemia, it typically presents with milder symptoms and a different metabolic profile than Von Gierke disease. *Phosphorylase* - **Glycogen phosphorylase** deficiency is associated with **McArdle's disease (GSD V)** in muscle and **Hers' disease (GSD VI)** in the liver. - These conditions primarily cause muscle weakness and cramping (McArdle's) or mild hypoglycemia and hepatomegaly (Hers'), but not the severe hypoglycemia and characteristic findings of Von Gierke disease.
Question 5: An adolescent male patient came with pain in calf muscles on exercise. On biopsy excessive amount of glycogen was found to be present in the muscle. What is the most likely enzyme deficiency?
- A. Glucose 6 phosphatase
- B. Phosphofructokinase I
- C. Phosphorylase enzyme (Correct Answer)
- D. Muscle debranching enzyme
Explanation: ***Phosphorylase enzyme*** - Deficiency of **muscle phosphorylase** (McArdle disease, glycogen storage disease type V) leads to the inability to break down glycogen in muscles, resulting in **exercise intolerance** and muscle pain due to **glycogen accumulation**. - Patients typically experience **cramps** and **fatigue** during physical activity, as glycogen cannot be mobilized for energy. *Glucose 6 phosphatase* - Deficiency of **glucose-6-phosphatase** (von Gierke disease, glycogen storage disease type I) primarily affects the **liver and kidneys**, causing **hypoglycemia** and **hepatomegaly**. - It does not directly cause muscle pain or glycogen accumulation in muscle tissue. *Phosphofructokinase I* - Deficiency of **phosphofructokinase I** (Tarui disease, glycogen storage disease type VII) also causes **exercise intolerance** and muscle pain, similar to McArdle disease. - However, it would result in an accumulation of **glucose-6-phosphate** and **fructose-6-phosphate**, not just excessive glycogen. *Muscle debranching enzyme* - Deficiency of the **muscle debranching enzyme** (Cori disease, glycogen storage disease type III) causes accumulation of **abnormal glycogen with short outer branches**. - While it affects muscle, symptoms including **muscle weakness** and occasional exercise intolerance, are typically less severe than in McArdle disease, and it's characterized by an atypical glycogen structure.
Question 6: Glycogen synthase is activated by?
- A. Insulin (Correct Answer)
- B. Glucagon
- C. AMP
- D. Epinephrine
Explanation: **Insulin** - Insulin activates **glycogen synthase** through a signaling cascade that dephosphorylates the enzyme, shifting it to its active form (glycogen synthase a). - This activation promotes **glycogen synthesis** in the liver and muscles, lowering blood glucose levels. *Glucagon* - **Glucagon** primarily acts to increase blood glucose levels by activating **glycogen phosphorylase** and inhibiting glycogen synthase. - It promotes the breakdown of glycogen (glycogenolysis) rather than its synthesis. *Epinephrine* - **Epinephrine** (adrenaline) also promotes **glycogenolysis** (glycogen breakdown) by activating glycogen phosphorylase. - Its main role is to provide rapid energy during stress, not to store glucose as glycogen. *AMP* - **AMP** (adenosine monophosphate) is a key allosteric activator of **AMP-activated protein kinase (AMPK)**, which phosphorylates and inactivates glycogen synthase. - High AMP levels signal a low energy state, prompting ATP-generating pathways like glycogenolysis, not glycogen synthesis.
Question 7: A person after consuming raw eggs presents with weakness, fatigue & hypoglycemia. Doctor gave him biotin supplements. Which biotin-dependent enzyme's reduced activity is most likely causing hypoglycemia in this patient:
- A. Pyruvate carboxylase (Correct Answer)
- B. Glucose 6 phosphatase
- C. Glycogen phosphorylase
- D. Phosphoenol pyruvate carboxykinase
Explanation: ***Pyruvate carboxylase*** - This enzyme is crucial for **gluconeogenesis**, converting **pyruvate to oxaloacetate**. Biotin deficiency, often caused by consuming **avidin** in raw eggs, impairs its activity, leading to reduced glucose production and **hypoglycemia**. - **Avidin** present in raw egg whites binds irreversibly to biotin, preventing its absorption and utilization, thereby affecting biotin-dependent enzymes. *Glucose 6 phosphatase* - This enzyme is involved in the final step of **gluconeogenesis** and **glycogenolysis**, releasing free glucose into the bloodstream. While its dysfunction can cause hypoglycemia, it is **not a biotin-dependent enzyme**. - Deficiencies in this enzyme are typically associated with **Von Gierke disease** (glycogen storage disease type I), which has distinct clinical features and is not related to raw egg consumption. *Glycogen phosphorylase* - This enzyme is responsible for the breakdown of **glycogen into glucose-1-phosphate** (**glycogenolysis**). Its inhibition would impair glycogen breakdown and could lead to hypoglycemia, but it is **not biotin-dependent**. - Deficiencies often present as **McArdle disease** (glycogen storage disease type V), characterized by exercise intolerance and muscle pain, which is not the primary presentation here. *Phosphoenol pyruvate carboxykinase* - This enzyme functions in **gluconeogenesis**, converting **oxaloacetate to phosphoenolpyruvate**. While essential for glucose production, it is **not a biotin-dependent enzyme**. - Its activity is regulated by hormones like glucagon and insulin, and its deficiency would impair gluconeogenesis, but the specific link to raw egg consumption and biotin is absent.
Question 8: Which of the following is a direct cause of ketosis in a patient with Von Gierke's disease?
- A. Inadequate glucose availability
- B. Increased ketone body production due to fatty acid oxidation
- C. Increased fatty acid oxidation (Correct Answer)
- D. Deficiency of glucose-6-phosphatase
Explanation: ***Increased fatty acid oxidation*** - In Von Gierke's disease, **glucose-6-phosphatase deficiency** leads to inability to release glucose from the liver, causing **hypoglycemia**. - The hypoglycemia triggers a hormonal response with **low insulin and high glucagon**, leading to lipolysis and fatty acid mobilization from adipose tissue. - These mobilized fatty acids undergo **β-oxidation in the liver**, generating excess **acetyl-CoA** that exceeds the capacity of the TCA cycle. - The excess acetyl-CoA is converted to **ketone bodies** (acetoacetate, β-hydroxybutyrate, acetone) - this is the **direct biochemical cause** of ketosis. *Inadequate glucose availability* - This is the **trigger** that initiates the metabolic shift, but not the direct biochemical cause of ketosis. - It creates the conditions that lead to fatty acid oxidation. *Deficiency of glucose-6-phosphatase* - This is the **primary enzyme defect** in Von Gierke's disease (GSD Type Ia). - It is the root cause but several metabolic steps removed from the actual production of ketone bodies. *Increased fatty acid mobilization* - This provides the **substrate** (fatty acids) that will be oxidized. - However, mobilization alone doesn't cause ketosis - the fatty acids must undergo **oxidation** in the liver to generate ketone bodies.
Question 9: Cardiomyopathy may be seen in all of the following conditions except.
- A. Duchenne muscular dystrophy
- B. Friedreich's ataxia
- C. Type II glycogen storage disease
- D. Alkaptonuria (Correct Answer)
Explanation: Detailed explanation of cardiomyopathy associations: ***Alkaptonuria*** - Alkaptonuria primarily affects **metabolization of tyrosine** and does not typically lead to cardiomyopathy. - The main clinical manifestation is **ochronosis**, causing dark urine and cartilage damage, without significant cardiac involvement. *Type II glycogen storage* - This condition, also known as **Pompe disease**, can lead to cardiomyopathy due to excessive glycogen accumulation in cardiac tissue. - Patients may exhibit **hypertrophic cardiomyopathy** as a common feature in infancy or early childhood. *Friedreich's ataxia* - This hereditary degenerative disease often leads to cardiac complications such as **hypertrophic cardiomyopathy** and conduction abnormalities [3]. - A classic presentation includes **ataxia** and **loss of deep tendon reflexes**, alongside possible cardiac involvement [2]. *Duchenne muscular dystrophy* - Duchenne muscular dystrophy is characterized by **progressive muscle weakness** and is frequently associated with **dilated cardiomyopathy** due to myocardial degeneration [1] [4]. - Affected individuals often show signs of cardiac dysfunction alongside muscle atrophy and weakness [1].
Question 10: Muscles cannot release free glucose from glycogen stores because of a deficiency of:
- A. Glucose-6-phosphatase (Correct Answer)
- B. Hexokinase
- C. Phosphoglucomutase
- D. Glycogen phosphorylase
Explanation: ***Glucose-6-phosphatase*** - **Glucose-6-phosphatase** is the enzyme that dephosphorylates glucose-6-phosphate to free glucose, allowing its release into the bloodstream. - This enzyme is **physiologically absent in muscle tissue** (present only in liver and kidneys), meaning muscles can break down glycogen for their own energy needs but cannot release free glucose into circulation. - This ensures that muscle glycogen stores are reserved exclusively for muscle's own metabolic needs during contraction. *Glycogen phosphorylase* - **Glycogen phosphorylase** is present in muscle and catalyzes the breakdown of glycogen by cleaving α-1,4 glycosidic bonds to release glucose-1-phosphate. - Muscles have this enzyme and can normally break down glycogen for energy; deficiency causes **McArdle disease** (glycogen storage disease type V) with exercise intolerance. *Hexokinase* - **Hexokinase** is abundant in muscle tissue and phosphorylates free glucose to glucose-6-phosphate for entry into glycolysis. - This enzyme is necessary for utilizing both blood glucose and glycogen-derived glucose-6-phosphate. *Phosphoglucomutase* - **Phosphoglucomutase** is present in muscle and converts glucose-1-phosphate (from glycogen breakdown) to glucose-6-phosphate. - This enzyme is essential for channeling glycogen-derived glucose into glycolysis.
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