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What is Pompe Disease?

Pompe Disease or Glycogen storage disease type 2 or Acid Maltase Deficiency Disease or Lysosomal Storage Disease (LSD) is a rare genetic and metabolic muscle disorder that affects 1 in 40,000 births in the USA. It has been named after the scientist, Dr. Joannes Pompe, who described it for the first time in the year 1932 in a 7-month old baby who died of cardiac hypertrophy (severe thickening of heart muscles). He also found accumulated glycogen (a stored form of sugar) in several tissues of the baby’s body, more prominently in the cardiac and skeletal muscles.

Later, it was found that the disease is a result of the deficiency of a lysosomal enzyme named acid alpha-glucosidase (GAA) whose function is to convert glycogen to glucose, the more useful form to the body for energy generation.

Development of the Disease:

Lysosomes are the structures within a cell that have enzymes to breakdown products of the cell. In Glycogen storage disease type 2 due to lack of the above mentioned enzyme, glycogen piles up inside the lysosomes. Excess glycogen accumulation eventually causes swelling and rupturing of the lysosomal membrane resulting in the spread out of its products and cellular damage.

The disease may develop in infants, children or adults who inherit a mutated (defective) gene one from each of the parents. Mutations in the GAA gene either decrease or completely remove the required enzyme and the accumulated glycogen usually impairs the functioning of muscle and heart cells.

Depending on the age of the onset and severity of the disease it has been classified as Classic infantile-onset, Non-classic infantile onset and Late-onset.

  • Classic infantile-onset – This form of the disease is observed in infants within a few months of birth. It is a result of near complete or complete deficiency of the GAA enzyme. Symptoms begin with problems in feeding and complicated lung infections. Babies experience hypotonia (poor muscle tone), myopathy (muscle weakness), heart defects and hepatomegaly (liver enlargement). Moreover, their growth is hampered and they face breathing difficulties. If this is not treated in time, the baby may not live to celebrate his/her first birthday because of heart failure.
  • Non-classic infantile-onset – This usually develops by the age of 1. Cardiomegaly (abnormal heart enlargement), progressive muscle weakness, retarded motor skills, tongue enlargement and respiratory complications are the symptoms of this form. Children with non-classic infantile-onset die in their early childhood.
  • Late-onset – This is a result of a partial deficiency of the GAA enzyme. In this form the symptoms may become apparent either in the late childhood or adolescence or in the adulthood. The symptoms in this form begin with muscle weakness specifically in the trunk and legs, which gradually progresses to respiratory weakness and eventually leads to the death of the person due to respiratory failure. Even if the heart is involved, enlargement is not seen.

It was observed that in infants suffering from Pompe Disease the levels of GAA were less than 1%. In children and adults the levels were ranging from 1% – 40% of the normal levels.

Course of the Disease:

In infants, accumulation levels of glycogen in skeletal muscles may be 10 times more than the normal levels. The progression of the disease is also very rapid in them and is marked by cardiomegaly.

In children and adults suffering from this disease, the disease progression is comparatively slow and very little or no involvement of cardiac related problems is seen.

Mode of Inheritance:

As mentioned in the earlier paragraphs, this is a genetic disorder that runs in families. It is inherited by the children from their parents in an autosomal recessive pattern. This implies that both copies of the GAA gene have mutations (defects). Children who receive 2 mutated genes develop the disease.

  • If they receive one normal gene and one mutated gene they are considered as carriers who do not exhibit any abnormalities. However, they do show low-GAA activity due to the presence of only 1 functional gene.
  • If both the parents are ‘carriers’, each child born to them has a 25% chance of not developing the disease, a 25% chance of developing the disease and a 50% chance of becoming a carrier.
  • If one parent is a carrier and the other has the disease, each child born to them has a 50% chance of becoming a carrier and a 50% chance of developing the disease.
  • If one parent has the disease and the other does not, children born to them will be carriers, but none of them will inherit the disease.

Diagnosis of Pompe Disease:

An enzyme assay test that determines the GAA enzyme activity is performed on the patients. The test is usually performed on the blood sample or tissue sample (skin, muscle) taken from the patient’s body. After the confirmation of the diagnosis, all family members of the patient are tested and carriers are identified by performing a genetic mutation analysis.

What Kind of Treatment is Available since it is a Genetic Disorder?

Specialist treatment is recommended for this condition. Treatment should be given by a team of specialists including a neurologist, a cardiologist and a respiratory therapist who can provide symptomatic treatment options.

Because this condition is a result of partial or complete deficiency of the enzyme GAA, doctors have come up with Enzyme Replacement Therapy (ERT) as the treatment option. Myozyme is the name of the drug used in ERT developed by the Genzyme Corporation. Clinical trials of ERT on infants have shown positive results in the form of reduced heart size, decreased glycogen accumulation, improved muscle strength, function and tone.

FDA has approved this drug and it is now available to the patients suffering from Pompe Disease throughout the world.

Gene Replacement Therapy is the ultimate goal of the researchers working on developing a cure for this condition.

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