CAUSE OF ACID MALTASE DEFICIENCY OR POMPE DISEASE
Pompe disease is caused by a complete or partial deficiency of the lysosomal enzyme, alpha-glucosidase. This enzyme is necessary to break down glycogen and to convert it into glucose. Without this enzyme, glycogen, a thick sticky substance, accumulates in the lysosomes (sacs within the muscle cells) and leads to severe muscle degradation. It predominately affects the heart, skeletal, and respiratory muscles of the patient.
Pompe disease was first described by Dr. Joannes Pompe (of the Netherlands) in 1936. Pompe patient Joseph Walter created the following presentation on Dr. Pompe:
PROGRESSION OF POMPE DISEASE
Patients with the infantile form of the disease are the most severely affected. These babies appear normal at birth, but exhibit symptoms by 2-3 months of age (or earlier). Progression is rapid. These patients are so severely affected that they become “limp” unable to feed or move. Their hearts become massively enlarged, and they typically die of cardio-respiratory failure before reaching 12 months of age.
In the delayed onset form progression of the disease is less rapid. Symptoms can manifest at any age of life and can greatly affect the quality of life as well as the life span of the afflicted person. Delayed onset patients that develop symptoms in childhood are more severely affected and typically die by the second or third decade of life. As the disease progresses, patients lose mobility, become wheelchair bound or bedridden. Respiratory functions greatly diminish and mechanical ventilation becomes necessary. Death results from cardio-respiratory complications.
CLINICAL FORMS OF POMPE DISEASE
Clinical forms of the disease vary according to the age of onset and percent of enzyme activity.
The Infantile Form – appears in the first few months after birth and is characterized by a rapid build-up of glycogen in muscle tissue causing severe muscle weakness and enlargement of the heart and liver. Respiratory and heart complications lead to death by the age of 12 months. The infantile form is characterized by a total lack of the alpha-glucosidase enzyme or by total inactivity of the enzyme.
The Delayed Onset Form – can present at any age. Delayed onset patients produce a minimal amount of enzyme. Progression and severity of the disease is probably attributable to the amount of enzyme produced and to the age of onset of symptoms. Glycogen build up is not as rapid as in the infantile form but the disease is progressive and can greatly decrease the life span of the afflicted person. In the delayed onset form deterioration of muscle is mainly confined to the skeletal muscles, the diaphragm, the limb-girdle, and the trunk. Respiratory complications are the main cause of death. Delayed onset patients that present symptoms early in life are usually more severely affected and rarely survive past the second or third decade of life. Patients that experience onset later in life generally progress at a slower pace.
ENZYME REPLACEMENT THERAPY
In 1999 the first human clinical trials for Pompe disease with enzyme replacement therapy began in the Netherlands with four infantile patients at Sophia Children’s Hospital in Rotterdam. Six months later another clinical trial was started in the Netherlands with three delayed onset patients. At the same time Duke University Medical Center in the US initiated a new infantile clinical trial with three patients.
Genzyme Corporation, the sponsor of these first clinical trials, received FDA and EMEA approval for enzyme replacement therapy for all Pompe patients in 2006.
GENE REPLACEMENT THERAPY.....
Gene replacement therapy will eventually be the cure for Pompe disease and other rare disorders. But until this dream is realized, enzyme replacement therapy offers hope in the near future for those affected by the devastation of Pompe disease.