Glycogen storage disease type II

Glycogen storage disease type II
Pompe vacuoles.jpg
Muscle biopsy showing large vacuoles typical of Pompe disease (HE stain, frozen section).
Synonyms	Pompe disease, acid maltase deficiency
Pronunciation	Pompe
Symptoms	Progressive muscle weakness, cardiomegaly, respiratory difficulties
Complications	Heart failure, respiratory failure
Usual onset	Varies (infantile to adult onset)
Duration	Lifelong
Types	Infantile-onset, late-onset
Causes	Deficiency of lysosomal acid alpha-glucosidase enzyme
Risk factors	Family history (autosomal recessive inheritance)
Diagnosis	Genetic testing, enzyme assay, muscle biopsy
Differential diagnosis	Other glycogen storage diseases, muscular dystrophies
Prevention	Genetic counseling
Treatment	Enzyme replacement therapy, supportive care
Prognosis	Varies widely, severe forms have reduced life expectancy
Frequency	Rare
Deaths	Rare, dependent on disease severity and management

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Autosomal recessive inheritance

Glycogen storage disease type II, also known as Pompe disease or acid maltase deficiency, is a rare, inherited metabolic disorder characterized by the accumulation of glycogen in body tissues due to a deficiency of the enzyme lysosomal acid alpha-glucosidase. This buildup results in progressive damage primarily to muscle and nerve tissues.

History

Pompe disease was first described in 1932 by the Dutch pathologist J.C. Pompe, marking it as the first identified glycogen storage disease. Pompe observed glycogen accumulation within muscle tissue in affected infants.

Classification

Pompe disease is classified into two main types:

• Infantile-onset Pompe disease: Severe, rapidly progressive form presenting within the first few months of life with marked cardiomegaly, muscle weakness, and respiratory issues.
• Late-onset Pompe disease: Presents in childhood, adolescence, or adulthood with a more gradual progression primarily affecting skeletal muscles and respiratory function.

Clinical Features

Common symptoms include:

• Progressive muscle weakness (myopathy)
• Respiratory difficulties
• Enlarged heart (cardiomegaly) primarily in infantile-onset
• Impaired motor skills and mobility

Pathophysiology

The deficiency of acid alpha-glucosidase enzyme disrupts lysosomal glycogen breakdown, causing excessive glycogen storage. Over time, this results in cellular dysfunction and muscle fiber damage, impacting skeletal, cardiac, and smooth muscle tissues.

Diagnosis

Diagnostic approaches include:

• Genetic testing to detect mutations in the GAA gene
• Enzyme assays to measure acid alpha-glucosidase activity
• Muscle biopsy showing glycogen accumulation and characteristic vacuoles

Treatment

Current treatment strategies include:

• Enzyme replacement therapy (ERT), specifically recombinant acid alpha-glucosidase, which can slow disease progression.
• Supportive therapies, including physical therapy, respiratory support, nutritional management, and cardiac care.

Prognosis

Prognosis varies significantly depending on the age of onset, severity, and timely initiation of treatment. Infantile-onset disease typically has a poor prognosis without early intervention, while individuals with late-onset forms may have a near-normal lifespan with appropriate management.

Prevention

Given the autosomal recessive inheritance, genetic counseling is recommended for families with a history of Pompe disease to evaluate risks for future offspring.

See Also

• Glycogen storage diseases
• Lysosomal storage disorders
• Metabolic disorders
• Enzyme replacement therapy