Glycogen Storage Diseases — MCQs

10 questions

A 6-month-old child presented with multiple episodes of seizures over the past 2.5 months. The child was admitted to the ward and had frequent episodes of hypoglycemia, which precipitated the seizures. On examination, hepatosplenomegaly, short stature, thin extremities, and a doll-like facies were noted. Laboratory findings revealed hyperuricemia, lactic acidosis, and hyperlipidemia. Which enzyme deficiency is responsible for this disorder?

Enzyme deficient in Hers disease -

Muscle phosphorylase deficiency leads to which glycogen storage disorder?

Glycogen storage disorders are primarily classified under which type of disorders?

Glycogen storage disorder due to muscle phosphorylase deficiency is which type of disease?

Which glycogen storage disease does not affect muscles?

Cardiomyopathy may be seen in all of the following conditions except.

Which of the following is a direct cause of ketosis in a patient with Von Gierke's disease?

Which of the following statements about the inheritance of an X-linked recessive trait is true?

Q10

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 Storage Diseases Indian Medical PG Practice Questions and MCQs

Question 1: A 6-month-old child presented with multiple episodes of seizures over the past 2.5 months. The child was admitted to the ward and had frequent episodes of hypoglycemia, which precipitated the seizures. On examination, hepatosplenomegaly, short stature, thin extremities, and a doll-like facies were noted. Laboratory findings revealed hyperuricemia, lactic acidosis, and hyperlipidemia. Which enzyme deficiency is responsible for this disorder?

A. Glucose-6-phosphatase (Correct Answer)
B. Acid maltase
C. Phosphofructokinase deficiency
D. Debranching enzyme deficiency
E. Branching enzyme

Explanation: ***Glucose-6-phosphatase*** - This enzyme deficiency leads to **Von Gierke's disease (Type I glycogen storage disease)**, characterized by severe **fasting hypoglycemia** due to the inability to release glucose from glycogen stores or perform gluconeogenesis. - The accumulation of glucose-6-phosphate shunts substrates towards **lactic acid**, **uric acid**, and **lipid** synthesis, explaining the **lactic acidosis, hyperuricemia, hyperlipidemia**, and resultant **hepatosplenomegaly** and **doll-like facies**. *Acid maltase* - This refers to **Pompe disease (Type II glycogen storage disease)**, which primarily affects **cardiac and skeletal muscles**, leading to **cardiomyopathy** and muscle weakness. - While it involves glycogen storage, **hypoglycemia** and the metabolic derangements seen in the patient (e.g., hyperuricemia, lactic acidosis) are **not characteristic features**. *Phosphofructokinase deficiency* - This is **Tarui disease (Type VII glycogen storage disease)**, a rare disorder affecting **muscle and red blood cells**, causing **exercise intolerance**, muscle pain, and hemolytic anemia. - While it affects glycolysis, it **does not typically present with severe hypoglycemia** or the specific metabolic characteristics like hyperuricemia and lactic acidosis noted in the child. *Debranching enzyme deficiency* - This is **Cori disease (Type III glycogen storage disease)**, which results in milder hypoglycemia, hepatomegaly, and myopathy. - The deficiency leads to the accumulation of **glycogen with short outer branches**, but the severe and persistent metabolic derangements (marked lactic acidosis, hyperuricemia) and consistent severe hypoglycemia described are **less characteristic** than in Von Gierke's disease. *Branching enzyme* - This is **Andersen disease (Type IV glycogen storage disease)**, a rare disorder characterized by **progressive liver cirrhosis** and **hepatosplenomegaly** starting in infancy. - Unlike Von Gierke's disease, it **does not present with hypoglycemia** as the primary feature, and the metabolic profile (hyperuricemia, lactic acidosis, hyperlipidemia) is **not typical**.

Question 2: Enzyme deficient in Hers disease -

A. Muscle phosphorylase
B. Liver phosphorylase (Correct Answer)
C. Acid maltase
D. Debranching enzyme

Explanation: ***Liver phosphorylase*** - Hers disease, also known as Glycogen Storage Disease Type VI, is specifically caused by a deficiency of **liver phosphorylase**. - This enzyme is crucial for the breakdown of **glycogen in the liver**, leading to an inability to release glucose into the bloodstream during fasting. *Muscle phosphorylase* - Deficiency of **muscle phosphorylase** (myophosphorylase) causes **McArdle disease** (Glycogen Storage Disease Type V), which primarily affects muscle energy. - Patients typically present with exercise intolerance, muscle pain, and cramps, not the hepatic symptoms seen in Hers disease. *Acid maltase* - Deficiency of **acid maltase** (also known as alpha-glucosidase) is responsible for **Pompe disease** (Glycogen Storage Disease Type II), a lysosomal storage disorder. - This enzyme deficiency leads to glycogen accumulation in lysosomes in various tissues, including muscle, liver, and heart, causing muscle weakness and cardiomyopathy. *Debranching enzyme* - A deficiency in the **debranching enzyme** (amylo-1,6-glucosidase) causes **Cori disease** or **Forbes disease** (Glycogen Storage Disease Type III). - This results in the accumulation of abnormally structured glycogen with short outer branches in the liver, muscle, and heart.

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: 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 5: Glycogen storage disorder due to muscle phosphorylase deficiency is which type of disease?

A. Pompe's disease
B. Andersen's disease
C. Tarui's disease
D. McArdle's disease (Correct Answer)

Explanation: ***McArdle's disease*** - This condition is also known as **Glycogen Storage Disease Type V**, which is specifically caused by a deficiency in **muscle phosphorylase** (myophosphorylase). - Patients typically present with exercise intolerance, muscle pain, and cramping due to the inability to break down muscle glycogen for energy. *Pompe's disease* - This is **Glycogen Storage Disease Type II**, caused by a deficiency in **acid alpha-glucosidase** (acid maltase). - It primarily affects the heart and skeletal muscles, leading to cardiomegaly and hypotonia, and is not a muscle phosphorylase deficiency. *Andersen's disease* - Also known as **Glycogen Storage Disease Type IV**, this results from a deficiency in **glycogen-branching enzyme**. - It leads to the accumulation of abnormal glycogen structures in the liver and muscles, causing liver cirrhosis and muscle weakness. *Tarui's disease* - This is **Glycogen Storage Disease Type VII**, caused by a deficiency in **phosphofructokinase-1 (PFK-1)**, an enzyme involved in glycolysis. - Like McArdle's, it presents with exercise intolerance and muscle pain, but the enzymatic defect is distinct from muscle phosphorylase.

Question 6: 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 7: 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 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: Which of the following statements about the inheritance of an X-linked recessive trait is true?

A. Fathers can transmit X-linked traits to their sons
B. 25% of sons of a carrier mother are affected
C. Carrier mothers have a 50% chance of transmitting the disease to their sons (Correct Answer)
D. 100% of daughters of a diseased father are affected

Explanation: ***Carrier mothers have a 50% chance of transmitting the disease to their sons*** - A mother who is a carrier for an **X-linked recessive trait** has one normal X chromosome and one X chromosome carrying the recessive allele. - Each son she has has a **50% chance** of inheriting the X chromosome with the recessive allele (and thus being affected) and a 50% chance of inheriting the normal X chromosome. *Fathers can transmit X-linked traits to their sons* - Fathers transmit their **Y chromosome** to their sons, not an X chromosome. - Therefore, fathers cannot directly transmit X-linked traits to their sons. *25% of sons of a carrier mother are affected* - This statement is incorrect; as explained above, a carrier mother has a **50% chance** of transmitting the affected X chromosome to each son. - The 25% probability typically applies to autosomal recessive inheritance, not X-linked. *100% of daughters of a diseased father are affected* - A diseased father (meaning he has the **X-linked recessive trait**) will pass his single X chromosome to all of his daughters. - Therefore, all his daughters will be **obligate carriers**, but they will only be affected if their mother also contributes an X chromosome with the recessive allele (which is rare for recessive traits).

Question 10: 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.

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