Classification

Glycogen storage disease type II (Pompe disease or Acid Maltase Deficiency)

Brief Description of the Disease

Inherited and often fatal disorder that disables the heart and skeletal muscles.  It is caused by mutations in a gene that makes an enzyme called acid alpha-glucosidase (GAA). In Pompe disease, mutations in the GAA gene reduce or completely eliminate this essential enzyme.  Excessive amounts of lysosomal glycogen accumulate everywhere in the body, but the cells of the heart and skeletal muscles are the most seriously affected.

Forms or Kinds

Early onset (or  the infantile form) is the result of complete or near complete deficiency of GAA.  Symptoms begin in the first months of life, with feeding problems, poor weight gain, muscle weakness, floppiness, and head lag. Respiratory difficulties are often complicated by lung infections.  The heart is grossly enlarged. Many infants with Pompe disease also have enlarged tongues.  Most babies die from cardiac or respiratory complications before their first birthday.

 Late onset (or juvenile/adult) Pompe disease is the result of a partial deficiency of GAA.  The onset can be as early as the first decade of childhood or as late as the sixth decade of adulthood.  The primary symptom is muscle weakness progressing to respiratory weakness and death from respiratory failure after a course lasting several years.  The heart is usu

Inheritance 

Autosomal Recessive Condition

Manifestation 

Infantile form.  Symptoms begins in the first month of life, with feeding problems,poor weight gain,muscle weakness, floppiness and head lag.  Respiratory difficulties are often complicated by lung infections.  The heart is grossly enlarged.  Many infants also have large tongues.  Most babies dies from cardiac or respiratory complications before their first birthday.

Juvenile/Adult Form.  The primary symptom is muscle weakness progressing to respiratory  weakness and death from respiratory failure after a course lasting several years.  The heart is not usually involved.

Incidence

1 for every  40,000

Diagnosis

Diagnosed by screening for the common mutations in the GAA gene, by measuring the level of the GAA enzyme in a blood sample, or by a muscle biopsy. Once a diagnosis is obtained, consultation with a geneticist and screening of other family members is recommended 

Prognosis

Without enzyme replacement therapy, the hearts of babies with infantile onset Pompe disease progressively thicken and enlarge.  These babies die before the age of one year from either cardiorespiratory failure or respiratory infection.  For individuals with late onset Pompe disease, the prognosis is dependent upon the age of onset.  In general, the later the age of onset, the slower the progression of the disease.  Ultimately, the prognosis is dependent upon the extent of respiratory muscle involvement. 

Treatment

  • Alglucosidase Alfa (Myozyme©), has received FDA approval for the treatment of infants and children.
  • Aglucosidase Alfa drug, Lumizyme©, has been approved for late-onset (non-infantile) Pompe disease.

References