GSD Type 2

Type II

Also known as Acid-maltase deficiency; Pompe disease

Defect: Deficiency in enzyme acid-α-glucosidase (GAA) causing glycogen accumulation in all tissues, although primarily in skeletal muscle (muscles used for movement) and heart muscles.

Cause: Mutation in the GAA gene on human chromosome 17q25.

Incidence: Estimated range from 1 in 40,000 to 1 in 100,000.

Signs & symptoms

• All forms of GSD II share the presence of myopathy (muscle weakness), and most patients have elevated creatine kinase(CK)

Infantile-onset (birth to 1 year old)

• Hypotonia (poor muscle tone)
• Feeding difficulties
• Macroglossia (large tongue)
• Hepatomegaly (enlarged liver)
• Rapidly progressive hypertrophic cardiomyopathy (rapid enlargement of heart muscles)
• In severe cases, death by age 1 year by cardiorespiratory failure is expected.

Juvenile-onset (usually present after 2 years old)

• Difficulty walking and delayed motor milestones.
• Progressive weakness
• Swallowing difficulties
• Death from respiratory failure in second decade occurs.

Adult-onset (second and seventh decades of life)

• Proximal muscle weakness, sometimes manifesting as exercise intolerance and orthopnea (difficulty breathing when not in upright position)

Diagnosis

• Muscle biopsy
• Electromyography
• GAA analysis
• Consideration of signs & symptoms especially in Infant-onset GSD II

Treatment

Standard Therapy – A high protein diet has had some benefits in patients with late-onset disease.

Investigational Therapies – Enzyme replacement, gene therapy