Glycogen Storage Diseases Lecture Notes

Case Introduction

• Patient: TS, 14-year-old male
• Symptoms: Muscle cramps, difficulty exercising, weakness, tiredness after 5 minutes of running, muscle pain, cramps in calves, reddish-brown urine
• Diagnosis: Suspected McArdle disease (Glycogen storage disease type 5)

Glycogen Storage Basics

• Glucose: Main energy source, stored as glycogen
• Glycogen: Large branched polymer of glucose, broken down by liver and muscles for glucose boost
• Glycogen Storage Diseases: Genetic defects causing accumulation of glycogen, leading to cell damage and dysfunction

Overview of Glycogen Storage Diseases

• Affected Organs: Liver and muscles
• Symptoms:
  • Liver: Hypoglycemia, liver failure, liver cancer
  • Muscles: Weakness, exercise intolerance, heart failure
• Inheritance: Autosomal recessive
• Detection: Positive PAS stain for liver/muscle biopsies

Common Glycogen Storage Diseases

Type 1: Von Gierke Disease

• Deficient Enzyme: Glucose-6-phosphatase
• Symptoms:
  • Severe fasting hypoglycemia
  • Hepatomegaly
  • Elevated blood lactate, cholesterol, triglycerides, uric acid
  • Poor growth, doll-like face, distended abdomen
  • Risk of seizures, coma, intellectual disability
  • Elevated cholesterol and triglycerides
  • Kidney disease, elevated uric acid
• Treatment:
  • Dietary modifications (unccooked corn starch)
  • Avoid lactose, fructose, sucrose
  • Medications for clinical manifestations

Type 2: Pompe Disease

• Deficient Enzyme: Acid α-glucosidase (acid maltase)
• Symptoms:
  • Hypotonia, muscle weakness
  • Cardiomyopathy, heart failure
  • Macroglossia
• Treatment:
  • Enzyme replacement therapy
  • Research on gene therapy

Type 3: Cori Disease

• Deficient Enzyme: Debranching enzyme (α-1,6-glucosidase)
• Symptoms:
  • Milder hypoglycemia
  • No lactic acidosis
  • Muscle symptoms possible
• Treatment:
  • Similar to von Gierke (dietary measures)
  • High-protein or ketogenic diet if muscle disease present

Type 5: McArdle Disease

• Deficient Enzyme: Muscle glycogen phosphorylase
• Symptoms:
  • Exercise intolerance, muscle cramps
  • Myoglobinuria (dark urine)
  • Second-wind phenomenon during exercise
• Treatment:
  • High carbohydrate diet
  • Simple sugars before exercise
  • Avoid intense exercise

Summary of Key Concepts

• Glycogen Storage Diseases: Genetic defects leading to glycogen buildup
• Affected Organs: Liver and muscle
• Common Types: von Gierke, Pompe, Cori, McArdle
• Diagnosis: Blood tests, enzyme assays, DNA testing
• Management: Mainly dietary, enzyme replacement for some types

Confidence Checklist

• Identify and understand common glycogen storage diseases and their presentation, enzyme deficiencies, and management.