Glycogen storage diseases (GSD) MCQs With Answer

Glycogen storage diseases (GSD) MCQs With Answer

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Glycogen storage diseases (GSD) MCQs With Answer offer B. Pharm students a focused review of glycogen metabolism defects, clinical features, biochemical markers, genetics, and pharmacologic/therapeutic options. This concise, keyword-rich introduction covers major types such as Von Gierke (Type I), Pompe (Type II), Cori (Type III), McArdle (Type V) and less common forms, emphasizing enzyme deficiencies, inheritance patterns, diagnostic tests (glucagon challenge, lactate, CK, PAS staining), and treatments including dietary management, enzyme replacement therapy and liver transplant. Clear, clinically relevant MCQs will strengthen understanding of pathophysiology, drug targets and patient management. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. Which enzyme deficiency causes Von Gierke disease (GSD Type I)?

  • Debranching enzyme (amylo-1,6-glucosidase)
  • Glucose-6-phosphatase
  • Glycogen phosphorylase (muscle isoform)
  • Lysosomal alpha-glucosidase

Correct Answer: Glucose-6-phosphatase

Q2. The hallmark biochemical findings in untreated Von Gierke disease include:

  • Hyperglycemia, low lactate, low uric acid
  • Hypoglycemia, lactic acidosis, hyperuricemia
  • Hypoglycemia, low triglycerides, low ketones
  • Normal glucose with increased creatine kinase

Correct Answer: Hypoglycemia, lactic acidosis, hyperuricemia

Q3. Which therapeutic approach is first-line for preventing fasting hypoglycemia in GSD Type I?

  • Daily enzyme replacement therapy with alglucosidase alfa
  • Frequent feeds including nocturnal cornstarch
  • High-intensity interval training
  • Allopurinol as sole therapy

Correct Answer: Frequent feeds including nocturnal cornstarch

Q4. Pompe disease (GSD Type II) primarily results from deficiency of which enzyme?

  • Liver glycogen phosphorylase
  • Lysosomal acid alpha-glucosidase (acid maltase)
  • Branching enzyme (glycogen brancher)
  • Phosphofructokinase (muscle)

Correct Answer: Lysosomal acid alpha-glucosidase (acid maltase)

Q5. A distinguishing clinical feature of Pompe disease in infants is:

  • Hepatomegaly with severe hypoglycemia
  • Progressive cardiomyopathy and hypotonia
  • Exercise intolerance without cardiac involvement
  • Hepatic cirrhosis in early childhood

Correct Answer: Progressive cardiomyopathy and hypotonia

Q6. Which laboratory test is useful to demonstrate glycogen accumulation in tissue biopsy?

  • Periodic acid–Schiff (PAS) staining with diastase sensitivity
  • Giemsa stain for nucleic acids
  • Silver impregnation for reticulin fibers
  • Prussian blue for iron

Correct Answer: Periodic acid–Schiff (PAS) staining with diastase sensitivity

Q7. Cori disease (GSD Type III) is caused by deficiency of which enzyme?

  • Debranching enzyme (amylo-1,6-glucosidase)
  • Glucose-6-phosphatase
  • Muscle glycogen phosphorylase
  • Branching enzyme

Correct Answer: Debranching enzyme (amylo-1,6-glucosidase)

Q8. A characteristic difference between Von Gierke (I) and Cori (III) disease is:

  • Cori has normal blood lactate levels after fasting; Von Gierke has lactic acidosis
  • Von Gierke presents with cardiomyopathy; Cori does not
  • Cori causes only muscle symptoms with no liver involvement
  • Von Gierke is X-linked; Cori is autosomal dominant

Correct Answer: Cori has normal blood lactate levels after fasting; Von Gierke has lactic acidosis

Q9. McArdle disease (GSD Type V) results from deficiency of which enzyme?

  • Muscle glycogen phosphorylase (myophosphorylase)
  • Hepatic glucokinase
  • Debranching enzyme
  • Glucose-6-phosphatase

Correct Answer: Muscle glycogen phosphorylase (myophosphorylase)

Q10. A useful clinical sign for McArdle disease is:

  • Rapid liver enlargement in infancy
  • “Second wind” phenomenon during exercise
  • Severe fasting hypoglycemia with seizures
  • Progressive neuropathy starting in childhood

Correct Answer: “Second wind” phenomenon during exercise

Q11. Which GSD is X-linked and commonly involves phosphorylase kinase defects causing hepatomegaly and growth retardation?

  • Type VI (Hers disease)
  • Type IX (Phosphorylase kinase deficiency)
  • Type IV (Andersen disease)
  • Type II (Pompe disease)

Correct Answer: Type IX (Phosphorylase kinase deficiency)

Q12. Andersen disease (GSD Type IV) pathology is best described as:

  • Excess normal glycogen accumulation in lysosomes
  • Accumulation of abnormally structured glycogen with fewer branches leading to cirrhosis
  • Isolated muscle cramps without hepatic involvement
  • Complete absence of glycogen in liver and muscle

Correct Answer: Accumulation of abnormally structured glycogen with fewer branches leading to cirrhosis

Q13. Which test differentiates hepatic from muscle forms of GSD by measuring blood glucose response?

  • Glucagon stimulation test
  • Serum CK after exercise
  • Urine reducing sugar test
  • Liver biopsy PAS stain

Correct Answer: Glucagon stimulation test

Q14. In Von Gierke disease, what is the typical response to glucagon injection after an overnight fast?

  • Marked rise in blood glucose
  • No significant increase in blood glucose
  • Immediate hypoglycemia worsening
  • Rapid decrease in lactic acid

Correct Answer: No significant increase in blood glucose

Q15. Which pharmacologic therapy is approved as enzyme replacement for infantile Pompe disease?

  • Alglucosidase alfa
  • Recombinant glucose-6-phosphatase
  • Debranching enzyme tablets
  • Phosphorylase kinase activator

Correct Answer: Alglucosidase alfa

Q16. A hallmark biochemical finding in McArdle disease after ischemic forearm exercise is:

  • Marked rise in lactate and normal ammonia
  • No increase in lactate with exaggerated ammonia increase
  • Marked rise in blood glucose
  • Decreased creatine kinase levels

Correct Answer: No increase in lactate with exaggerated ammonia increase

Q17. Which dietary modification is commonly recommended for patients with GSD Type III to improve hypoglycemia and muscle symptoms?

  • High-protein diet with frequent meals
  • Strict ketogenic diet only
  • Complete avoidance of carbohydrates
  • Low-protein, high-fat diet

Correct Answer: High-protein diet with frequent meals

Q18. The genetic inheritance pattern for most classic glycogen storage diseases is:

  • Autosomal dominant
  • X-linked dominant
  • Autosomal recessive
  • Mitochondrial inheritance

Correct Answer: Autosomal recessive

Q19. Which GSD commonly presents with hemolytic anemia and muscle cramps due to phosphofructokinase deficiency?

  • Type II (Pompe)
  • Type VII (Tarui disease)
  • Type I (Von Gierke)
  • Type IV (Andersen)

Correct Answer: Type VII (Tarui disease)

Q20. In hepatic phosphorylase deficiency (Hers disease, Type VI), typical clinical features include:

  • Severe lactic acidosis and cardiomyopathy
  • Mild fasting hypoglycemia and hepatomegaly
  • Progressive neuromuscular degeneration
  • Renal glycosuria and polyuria

Correct Answer: Mild fasting hypoglycemia and hepatomegaly

Q21. Which imaging or histologic finding is characteristic of Pompe disease muscle biopsy?

  • Excess cytosolic glycogen that is diastase resistant
  • Lysosomal glycogen accumulation with vacuolation
  • Complete absence of glycogen on PAS staining
  • Aggregates of abnormal branched glycogen in nucleus

Correct Answer: Lysosomal glycogen accumulation with vacuolation

Q22. Which laboratory marker is most likely elevated in muscle forms of GSD such as McArdle disease?

  • Alkaline phosphatase
  • Serum creatine kinase (CK)
  • Serum bilirubin
  • Serum albumin

Correct Answer: Serum creatine kinase (CK)

Q23. Which GSD is most likely to present with severe fasting hypoglycemia, lactic acidosis, hypertriglyceridemia and doll-like facies in infancy?

  • Von Gierke disease (Type I)
  • McArdle disease (Type V)
  • Cori disease (Type III)
  • Andersen disease (Type IV)

Correct Answer: Von Gierke disease (Type I)

Q24. A distinguishing biochemical test for Type I GSD is persistent high lactate; what is the mechanism?

  • Excess gluconeogenesis consuming lactate
  • Block in final step of gluconeogenesis and glycogenolysis causing lactate accumulation
  • Increased utilization of lactate by muscle
  • Renal loss of lactate leading to compensatory overproduction

Correct Answer: Block in final step of gluconeogenesis and glycogenolysis causing lactate accumulation

Q25. Which complication is common in adolescent and adult patients with poorly controlled GSD Type I?

  • Progressive cardiomyopathy requiring ERT
  • Gout and renal stones due to hyperuricemia
  • Peripheral neuropathy with sensory loss
  • Osteoporosis without metabolic causes

Correct Answer: Gout and renal stones due to hyperuricemia

Q26. For which GSD is liver transplantation considered as a definitive treatment option?

  • Type V (McArdle disease)
  • Type I (Von Gierke) and some severe Type III cases
  • Type II (Pompe) only
  • Type VII (Tarui) only

Correct Answer: Type I (Von Gierke) and some severe Type III cases

Q27. Which enzyme abnormality leads to an abnormal glycogen with very few branches and progressive liver cirrhosis?

  • Branching enzyme deficiency (Andersen disease)
  • Debranching enzyme deficiency (Cori disease)
  • Muscle phosphorylase deficiency (McArdle)
  • Glucose-6-phosphatase deficiency (Von Gierke)

Correct Answer: Branching enzyme deficiency (Andersen disease)

Q28. Which biochemical feature helps to differentiate Cori disease from Von Gierke disease?

  • Presence of cardiomyopathy in Cori only
  • Normal fasting lactate in Cori; elevated lactate in Von Gierke
  • McArdle has hepatic symptoms unlike Cori
  • Cori shows high glucose response to glucagon

Correct Answer: Normal fasting lactate in Cori; elevated lactate in Von Gierke

Q29. In Tarui disease (GSD Type VII), which metabolic pathway is primarily affected?

  • Gluconeogenesis via fructose-1,6-bisphosphatase
  • Glycolysis due to muscle phosphofructokinase deficiency
  • Glycogenolysis via lysosomal alpha-glucosidase
  • Beta-oxidation of fatty acids

Correct Answer: Glycolysis due to muscle phosphofructokinase deficiency

Q30. Which exam finding is typical in a muscle biopsy from McArdle disease?

  • Clear vacuoles containing PAS-positive material within lysosomes
  • Increased subsarcolemmal glycogen and PAS-positive cytosolic glycogen
  • Extensive fibrosis without glycogen accumulation
  • Normal histology in most cases

Correct Answer: Increased subsarcolemmal glycogen and PAS-positive cytosolic glycogen

Q31. Which clinical intervention can provide symptomatic relief for exercise intolerance in McArdle disease?

  • Oral sucrose taken before exertion
  • Beta-blockers prior to exercise
  • High-dose corticosteroids during activity
  • Daily cornstarch supplementation only at night

Correct Answer: Oral sucrose taken before exertion

Q32. Which GSD is most likely to be identified by newborn screening for elevated biomarkers or enzyme assays?

  • Pompe disease (infantile form)
  • McArdle disease (Type V)
  • Andersen disease (Type IV)
  • Hers disease (Type VI)

Correct Answer: Pompe disease (infantile form)

Q33. Glycogen in lysosomes rather than cytosol is the hallmark of which GSD?

  • Von Gierke disease (Type I)
  • Pompe disease (Type II)
  • McArdle disease (Type V)
  • Andersen disease (Type IV)

Correct Answer: Pompe disease (Type II)

Q34. What is the molecular target for cellular uptake of many recombinant enzyme replacement therapies?

  • Mannose-6-phosphate receptor
  • Insulin receptor
  • Toll-like receptor 4
  • Glucose transporter 4 (GLUT4)

Correct Answer: Mannose-6-phosphate receptor

Q35. Severe hypoglycemia unresponsive to glucagon but responsive to IV dextrose is typical for which GSD?

  • Von Gierke disease (Type I)
  • McArdle disease (Type V)
  • Hers disease (Type VI)
  • Tarui disease (Type VII)

Correct Answer: Von Gierke disease (Type I)

Q36. Which biochemical disturbance is frequently seen in GSD Type I and contributes to hypertriglyceridemia?

  • Excessive insulin secretion causing lipogenesis
  • Accumulation of glucose-6-phosphate driving de novo lipogenesis
  • Defect in fatty acid oxidation only
  • Renal loss of triglycerides

Correct Answer: Accumulation of glucose-6-phosphate driving de novo lipogenesis

Q37. Which enzymatic assay would you order to confirm McArdle disease from a muscle biopsy?

  • Assay for acid alpha-glucosidase
  • Assay for myophosphorylase (muscle glycogen phosphorylase)
  • Assay for hepatic glucose-6-phosphatase
  • Assay for branching enzyme

Correct Answer: Assay for myophosphorylase (muscle glycogen phosphorylase)

Q38. Which statement about GSD Type IX (phosphorylase kinase deficiency) is TRUE?

  • It is commonly autosomal dominant and causes severe neonatal hypoglycemia
  • It can be X-linked and often presents with mild hepatomegaly and growth delay
  • It primarily causes cardiomyopathy and respiratory failure
  • It is treated effectively with immediate enzyme replacement therapy

Correct Answer: It can be X-linked and often presents with mild hepatomegaly and growth delay

Q39. Which clinical laboratory pattern suggests a muscle GSD rather than a hepatic GSD?

  • Marked fasting hypoglycemia with lactic acidosis
  • Elevated CK and exercise-induced myoglobinuria with normal fasting glucose
  • Persistent hyperuricemia and hyperlipidemia
  • Severe hepatomegaly and growth retardation only

Correct Answer: Elevated CK and exercise-induced myoglobinuria with normal fasting glucose

Q40. Which drug or supplement has evidence for symptomatic benefit in some muscle GSDs by improving exercise tolerance?

  • Allopurinol
  • Creatine supplementation
  • Statins
  • High-dose vitamin D

Correct Answer: Creatine supplementation

Q41. The presence of limit-dextrin-like structures in liver biopsy suggests deficiency of which enzyme?

  • Debranching enzyme (Cori disease)
  • Lysosomal alpha-glucosidase (Pompe)
  • Muscle phosphorylase (McArdle)
  • Glucose-6-phosphatase (Von Gierke)

Correct Answer: Debranching enzyme (Cori disease)

Q42. What is the rationale for using frequent complex carbohydrate feeds in hepatic GSDs?

  • To suppress gluconeogenesis completely
  • To maintain euglycemia and prevent catabolism during fasting
  • To stimulate lysosomal glycogen breakdown
  • To increase muscle glycogen synthesis exclusively

Correct Answer: To maintain euglycemia and prevent catabolism during fasting

Q43. Which GSD is associated with progressive myopathy and respiratory failure in adults due to late-onset presentation?

  • Late-onset Pompe disease (Type II)
  • Von Gierke disease (Type I)
  • Andersen disease (Type IV)
  • Tarui disease (Type VII)

Correct Answer: Late-onset Pompe disease (Type II)

Q44. Which metabolic consequence is commonly observed in patients with GSD Type I that influences pharmacologic choices?

  • Severe hyperkalemia requiring potassium-wasting diuretics
  • Hyperuricemia that may require xanthine oxidase inhibitors
  • Chronic hypomagnesemia requiring supplements
  • Excessive protein catabolism needing anabolic steroids

Correct Answer: Hyperuricemia that may require xanthine oxidase inhibitors

Q45. Genetic testing for mutations in which gene would confirm Pompe disease diagnosis?

  • GYS2 (liver glycogen synthase)
  • GAA (acid alpha-glucosidase)
  • PYGM (muscle glycogen phosphorylase)
  • GBE1 (glycogen branching enzyme)

Correct Answer: GAA (acid alpha-glucosidase)

Q46. Which clinical management is CONTRAINDICATED or risky in patients with McArdle disease?

  • Encouraging gradual aerobic exercise to reach “second wind”
  • Administering statins without monitoring due to increased myopathy risk
  • Using oral sucrose before exercise
  • Supplementing creatine in monitored doses

Correct Answer: Administering statins without monitoring due to increased myopathy risk

Q47. Which neonatal sign should prompt immediate evaluation for infantile Pompe disease?

  • Isolated hepatomegaly without cardiomyopathy
  • Poor feeding, hypotonia and hypertrophic cardiomyopathy
  • Early jaundice that resolves in a week
  • Excessive spontaneous movements

Correct Answer: Poor feeding, hypotonia and hypertrophic cardiomyopathy

Q48. Which laboratory pattern is typical for hepatic phosphorylase deficiency (Hers disease)?

  • Severe lactic acidosis and hyperammonemia
  • Mild hypoglycemia, elevated transaminases, and hepatomegaly
  • Marked hyperglycemia and low triglycerides
  • High CK with exercise-induced myoglobinuria

Correct Answer: Mild hypoglycemia, elevated transaminases, and hepatomegaly

Q49. Which of the following is a potential future therapeutic approach under investigation for several GSDs?

  • Antibiotic regimens to clear glycogen
  • Gene therapy to correct defective enzyme genes
  • Permanent fasting to reduce glycogen stores
  • Chronic steroid injections into muscle

Correct Answer: Gene therapy to correct defective enzyme genes

Q50. When counseling a family about recurrence risk for an autosomal recessive GSD, what is the recurrence risk for each subsequent pregnancy if both parents are carriers?

  • 25%
  • 50%
  • 75%
  • 0% if previous child affected

Correct Answer: 25%

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