About Pompe

How Do You Get Pompe Disease?

Pompe disease is inherited as an autosomal recessive disorder. The term autosomal implies that males and females have an equal chance of being affected. Recessive means that in order to get Pompe disease, an individual has to inherit two faulty copies of the Pompe disease (GAA) gene. Children usually inherit 1 copy of any particular gene from each parent. The mutant GAA gene (trait) can be passed on from unaffected parents (carriers) to their children. The likelihood of children born from Pompe disease carrier parents to suffer the disease is 25% (1 out of 4). Parents who carry a faulty copy of the GAA gene also have a normal copy of the gene. One normal copy of the gene generates enough GAA activity to prevent excess storage of lysosomal glycogen.
Incidence (Frequency):
Pompe disease is very rare. The incidence, or the chance of being born with Pompe disease, is estimated at about one in every forty thousand live births. The estimated frequency of Pompe disease may vary among different ethnic groups and nationalities:
Holland: 1 in 40,000.
(Adults: 1 in 57,000; Infantile: 1 in 138,000)
Southern China and Taiwan: 1 in 50,000 births
African-Americans: 1 in 14,000 births
Caucasian: 1 in 100,000

Assuming a disease frequency of 1 in 40,000 births, the number of people with Pompe disease worldwide is estimated to be somewhere between 5,000 and 10,000 cases.
Diagnosis
Pompe disease, like many other LSDs, is a rare disorder. Therefore consultation with specialists that are more familiar with this disease who use qualified laboratories to perform diagnostic tests may expedite the diagnostic process and the implementation of symptom management. Pompe disease diagnosis is usually based on, but not restricted to, the following criteria:

1. Natural history

Progressive generalized muscle weakness (All types)

Heart hypertrophy and macroglossia (Early onset)

Motor developmental delay (Prominent in Early onset) or regression of acquired motor skills (All types)

Previously diagnosed or symptomatic siblings or other relatives

2. Decreased/absent GAA activity in muscle or skin biopsies by qualified laboratories

3. Histopathology: Multivesicular PAS (+) storage in muscle tissue

4. GAA gene mutation(s) in patient's DNA .

Individuals who are the most severely affected by Pompe disease will have symptoms by two to three months of age

Health Canada approves Myozyme® for the treatment of Pompe DiseaseMississauga, ON - December 7, 2006– Following the August 2006 approval by Health1.2.3. Disease progression is rapid and these infants rarely live beyond one year of age. For others with Pompe disease, the disease onset may occur in childhood or adolescence, or later as an adult. The longer an individual with Pompe disease has symptoms, the earlier they will become wheelchair or ventilator dependent.4
-moreSymptoms

vary depending on the severity of the disease and the age of symptom onset.Infants exhibit a severe lack of muscle tone, often characterized as “floppy baby”syndrome, their heart is also affected and usually becomes enlarged – up to three times its normal size – and they usually die from cardiac or respiratory complications before one year of age. In older patients, symptoms are typically generalized muscle weakness, including skeletal, which may require the need for a wheelchair and other assistive devices, and respiratory, which may require mechanical ventilation.

Basis of Approval

5
A pivotal randomized, multi-centre clinical study (AGLU01602) of Myozyme demonstrated the product’s safety and efficacy. Initiated in 2003, the trial enrolled 18 patients with infantile-onset Pompe disease, who began receiving therapy at approximately six months of age. In the study, 83 per cent of individuals treated with Myozyme were both alive and free of invasive ventilator support at 18 months of age.By comparison, only 2 per cent of individuals in an untreated historical group were alive at 18 months.

6
About Myozyme

The development of Myozyme from recombinant DNA technology is a process that takes many months in specially built bio-reactors. Genetically modified cells are grown in large tanks over several months. Kept in constant motion, the cells multiply in this living production facility and begin to express the recombinant human protein. Liquid is drawn off daily and the enzyme is collected for a multi-stage purification process to isolate and purify the desired protein.

Genzyme began developing a treatment for Pompe disease in 1998. Today, more than 450 individuals in 30 countries are being treated with Myozyme through clinical trials,expanded access programs, charitable access programs, pre-approval regulatory mechanisms, or commercially

7.
About the Pompe Disease Registry

To further global understanding and awareness of Pompe disease, Genzyme created the Pompe Disease Registry, which documents the natural course of the disease,significant clinical outcomes, and disease management practices. More than 150 physicians and healthcare associates from around the world actively participate in the Pompe Registry, which has enrolled more than 250 people with Pompe disease.

About Genzyme

Genzyme Corporation is a biotechnology and health care products company that develops innovative products and services for major unmet medical needs. Celebrating ten years in this country, Genzyme Canada Inc., located in Mississauga, Ontario is the Canadian affiliate of Genzyme Corp., headquartered in Cambridge, Massachusetts.Myozyme is the fourth enzyme replacement therapy developed by Genzyme for a rare genetic disease. Genzyme has developed

PrFabrazyme® (agalsidase beta) for Fabry disease, PrCerezyme® (imiglucerase) for Type 1 and Type 3 Gaucher disease and, in collaboration with BioMarin Pharmaceutical Inc., PrAldurazyme® (laronidase) for MPS I.
1 Acid Maltase Deficiency Association (AMDA). Accessed November 30, 2006.

2 www.pompecanada.com

4 Study # AGLU01602; Randomized, Open-label, Multicenter, Safety, Efficacy, Pharmacokinetic and pharmacodynamic, Dose Ranging Study of Myozyme in 18 Pompe patients with a mean age of 4.6 months

5 Kishnani P, Corzo D, Nicolino M, et al. Recombinant human acid a-glucosidase: major clinical benefits in infantile-onset