Overview

• Definition: Glycogen Storage Diseases are a group of inherited metabolic disorders caused by deficiencies in enzymes involved in glycogen synthesis, degradation, or regulation.

• Inheritance: Mostly autosomal recessive, except for GSD IX (X-linked in some cases).

• General Symptoms: Hypoglycemia, hepatomegaly, growth retardation, muscle weakness, and metabolic imbalances depending on the type.

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Classification and Key Types

1. GSD Type I (von Gierke Disease)

   • Enzyme Deficiency: Glucose-6-phosphatase.

   • Pathophysiology: Impaired conversion of glucose-6-phosphate to glucose, leading to glycogen accumulation in liver and kidneys.

   • Symptoms: Severe hypoglycemia, lactic acidosis, hyperuricemia, hyperlipidemia, hepatomegaly, kidney enlargement.

   • Treatment: Frequent meals, cornstarch therapy, avoid fasting.

2. GSD Type II (Pompe Disease)

   • Enzyme Deficiency: Acid alpha-glucosidase (lysosomal enzyme).

   • Pathophysiology: Glycogen accumulation in lysosomes, particularly in muscles and heart.

   • Symptoms: Muscle weakness, cardiomyopathy, respiratory failure (infantile form); limb-girdle weakness (adult form).

   • Treatment: Enzyme replacement therapy (alglucosidase alfa).

3. GSD Type III (Cori or Forbes Disease)

   • Enzyme Deficiency: Amylo-1,6-glucosidase (debranching enzyme).

   • Pathophysiology: Accumulation of abnormal glycogen (limit dextrin) due to inability to remove branches.

   • Symptoms: Hepatomegaly, hypoglycemia, muscle weakness, mild compared to Type I.

   • Treatment: High-protein diet, cornstarch therapy.

4. GSD Type V (McArdle Disease)

   • Enzyme Deficiency: Muscle phosphorylase.

   • Pathophysiology: Inability to break down glycogen in skeletal muscle.

   • Symptoms: Exercise intolerance, muscle cramps, myoglobinuria (rhabdomyolysis risk).

   • Treatment: Avoid strenuous exercise, carbohydrate intake before activity.

5. Other Types:

   • GSD IV (Andersen Disease): Branching enzyme deficiency, leading to abnormal glycogen causing liver cirrhosis.

   • GSD VI (Hers Disease): Liver phosphorylase deficiency, milder hepatomegaly and hypoglycemia.

   • GSD IX: Phosphorylase kinase deficiency, often mild, affects liver or muscle.

Diagnosis

• Methods: Enzyme activity assays, genetic testing, liver/muscle biopsy, blood tests (glucose, lactate, lipids, uric acid).

• Challenges: Overlapping symptoms require specific enzyme or genetic confirmation.

Management

• Dietary: Frequent feeds, uncooked cornstarch, high-protein diets (for some types).

• Medical: Enzyme replacement (Type II), allopurinol (for hyperuricemia in Type I), supportive care for complications.

• Monitoring: Regular checks for hypoglycemia, liver size, kidney function, and muscle damage.

Complications

• Type-Specific: Liver adenomas/carcinoma (Type I), heart failure (Type II), cirrhosis (Type IV), rhabdomyolysis (Type V).

• General: Growth failure, osteoporosis, renal dysfunction.

Multiple Choice Questions (MCQs)

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1. Which enzyme is deficient in von Gierke disease (GSD Type I)?
   a) Acid alpha-glucosidase
   b) Glucose-6-phosphatase
   c) Amylo-1,6-glucosidase
   d) Muscle phosphorylase
   Answer: b) Glucose-6-phosphatase

2. What is a hallmark symptom of Pompe disease (GSD Type II)?
   a) Severe hypoglycemia
   b) Cardiomyopathy
   c) Liver cirrhosis
   d) Myoglobinuria
   Answer: b) Cardiomyopathy

3. Which GSD type is associated with exercise intolerance and muscle cramps?
   a) Type I
   b) Type III
   c) Type V
   d) Type IX
   Answer: c) Type V

4. What is the primary treatment for hypoglycemia in GSD Type I?
   a) Enzyme replacement therapy
   b) High-protein diet
   c) Frequent meals and cornstarch therapy
   d) Allopurinol
   Answer: c) Frequent meals and cornstarch therapy

5. Which GSD type results in the accumulation of abnormal glycogen (limit dextrin)?
   a) Type II
   b) Type III
   c) Type IV
   d) Type VI
   Answer: b) Type III