glycogen storage disease type-II (Pompe type glycogen storage disease, infantile acid maltase deficiency)

Introduction

Adult, juvenile & infant types.

Epidemiology

• rare genetic disorder
• 1 in 40,000 births

Pathology

• deficiency in alpha-1,4-glucosidase (GAA)
• build-up of glycogen
• affects heart, skeletal muscles, liver, & nervous system

Genetics

• autosomal recessive inheritance
• defects in alpha-1,4-glucosidase gene

Clinical manifestations

progressive muscle weakness

3 forms defined by age of onset & progression of symptoms

• infantile, or early onset, noticed shortly after birth
  • severe hypotonia, muscle weakness, hepatomegaly, cardiomegaly
  • mental function is not affected
  • dysphagia
  • tongue may protrude and become enlarged
  • development appears normal for the first weeks or months but slowly declines as the disease progresses
  • most children die from respiratory or cardiac complications before 2 years of age
• juvenile onset symptoms appear in early to late childhood
  • progressive weakness of respiratory muscles in the trunk, diaphragm
  • lower limb weakness
  • exercise intolerance
  • intelligence is normal
  • most patients do not live beyond the 2nd or 3rd decade of life
• adult onset
  • generalized muscle weakness
    • proximal muscle weakness
      • difficulty in climbing stairs
  • wasting of respiratory muscles in the trunk & diaphragm
  • respiratory distress
  • headache at night or upon waking
  • diminished deep tendon reflexes
  • intellect is not affected
  • a small number of adult patients live without major symptoms or limitations

Laboratory

• GAA gene mutation

Diagnostic procedures

• normal response of plasma glucose to IM glucagon

Management

• alglucosidase alfa (Myozyme, Lumizyme) or avalglucosidase alfa-ngpt (Nexviazyme)
  • cipaglucosidase alfa-atga (Pombiliti) + miglustat (Opfolda) for adult type
• cardiac & respiratory complications are treated symptomatically
• physical therapy
• occupational therapy
• changes in diet may provide temporary improvement but will not alter the course of the disease
• genetic counseling
• prognosis
  • varies according to the onset and severity of symptoms
  • particularly lethal in infants & young children

More general terms

• glycogen storage disease (glycogenosis)

Additional terms

• lysosomal alpha-glucosidase; alpha-1,4-glucosidase; acid alpha glucosidase; acid maltase (GAA)

Patient information

glycogen storage disease type-2 (Pompe type) patient information

Database

• OMIM: https://mirror.omim.org/entry/300257