Pompe's Glycogen Storage Disease

Synonyms: Glycogen storage disease type II; acid maltase deficiency

Pompe's disease is one of the glycogen storage disorders. The deficiency of the lysosomal enzyme alpha-1,4-glucosidase (acid maltase) leads to the accumulation of glycogen in many tissues:

• The clinical spectrum is continuous and broad, with presentation in infants, children and adults.¹
• In the infantile form, accumulation of glycogen in cardiac muscle leads to cardiac failure.
• Accumulation may also occur in the liver, which results in hepatomegaly and elevation of hepatic enzymes.
• Glycogen accumulation in muscle and peripheral nerves causes hypotonia and weakness.
• Glycogen deposition in blood vessels may result in intracranial aneurysms.

• The overall prevalence has been estimated at 1 in 40,000, with 1 in 138,000 for the infantile form and 1 in 57,000 for the adult form.²
• Infantile and adult forms are inherited as autosomal recessive conditions. The gene has been traced to chromosome 17.³

• Presentation later in life is associated with a less severe form of disease.
• There is a continuous spectrum between the classic infantile and adult forms.
• The infantile form presents with hypotonia at any time after birth, but usually presents at between 4-8 weeks.
• The adult form usually presents as skeletal and respiratory muscle weakness. The typical age of presentation is 20-40 years.

Symptoms

• The infantile form may present with feeding and breathing difficulties and dyspnoea.
• May present with muscle weakness later in childhood.
• The adult form may have limb-girdle weakness and weakness of respiratory muscles.⁴

Signs

• Infantile form:
  • Cardiomegaly and congestive heart failure.
  • Generalised hypotonia, absent or reduced reflexes.
  • Enlarged tongue.
  • Reflexes may be depressed or absent because of glycogen accumulation in spinal motor neurons.
  • Alertness may be impaired.
• Adult form:
  • Weakness may affect only specific muscle groups, e.g. upper arms, and may be asymmetrical.
  • Limb-girdle weakness is common and respiratory muscle involvement may be prominent.⁵

• Other glycogen storage disorders.
• Muscular dystrophy: Duchenne's muscular dystrophy (or less severe muscular dystrophies for older onset disease).

• Serum creatine kinase and aspartate aminotransferase are elevated.⁶
• Acid maltase levels are reduced in cultured skin fibroblasts.³
• Intracranial aneurysms may be shown on angiography or magnetic resonance angiography.
• Echocardiogram to assess heart size and degree of left ventricular hypertrophy.
• ECG: Short PR interval and elevated QRS complexes in the infantile form.
• Muscle biopsy for the evaluation of differential diagnosis of muscle weakness.

• No specific treatment exists and current management is focused on supportive care.
• Diet therapy may be helpful: a high-protein, low carbohydrate diet may be beneficial.⁷
• Recombinant human acid alpha-glucosidase enzyme therapy has been shown to improve cardiac and skeletal muscle function.^8,9
• Gene therapy remains a potentially effective treatment for the future.¹⁰

• In the infantile form, cardiomegaly and congestive heart failure lead to death.
• Cardiomegaly with progressive obstruction to left ventricular outflow is a major cause of mortality.
• Weakness of ventilatory muscles increases the risk of pneumonia.
• The adult form manifests with dystrophy and respiratory muscle weakness.
• In the adult form, intracranial aneurysms present the greatest complication.
• Liver failure may occur.

• The infantile form usually is fatal, with most deaths occurring within 1 year of birth.¹¹
• Later clinical onset usually corresponds with more benign symptoms and disease course.
• The adult form is not necessarily fatal, but complications such as rupture of an aneurysm or respiratory failure may cause significant morbidity and mortality.