Pompe disease

WHAT IS POMPE DISEASE?

Pompe disease is a severe neuromuscular disorder characterized by the deterioration of skeletal, respiratory, and cardiac muscles. It is caused by mutations in the GAA gene, which lead to a deficiency or complete absence of a specific enzyme. This deficiency allows glycogen to accumulate in the muscles, further impairing their function. To manage this condition, patients with Pompe disease typically receive enzyme replacement therapy, which supplements the missing GAA enzyme.

TYPES OF POMPE DISEASE

Pompe disease is classified into two types:

  1. Infantile Onset Pompe Disease (IOPD): This type appears within the first few months of life, characterized by general muscle weakness, including the respiratory and heart muscles (cardiomyopathy). Without enzyme replacement therapy (ERT), affected infants typically do not survive beyond their first year.
  2. Late Onset Pompe Disease (LOPD): This variant can begin in childhood or adulthood, predominantly affecting skeletal and respiratory muscles, often leading to dependency on wheelchairs or ventilators. The heart is usually not affected. The earlier Pompe disease manifests, the more severe the outcomes.

WHAT IS THE INCIDENCE?

Pompe disease is a rare disorder, incidence is approximately one every 40,000 births.

CAUSES

Pompe disease results from a metabolic disturbance in the skeletal, respiratory, and heart muscles due to a deficiency of the enzyme acid alpha-glucosidase (GAA). This enzyme is responsible for breaking down glycogen into glucose, which serves as energy for the body. Without sufficient GAA, glycogen accumulates in the muscle cells, causing damage and leading to muscle weakness.

SYMPTOMS

Pompe disease symptoms primarily include muscle weakness affecting lower limbs, respiratory muscles, and, in infants, the heart muscle. This leads to fatigue, pain, and varying complications depending on the disease type.
Classic form affects infants with severe muscle weakness, feeding difficulties, respiratory issues, and enlarged organs such as the heart and liver.
Non-classic form develops more gradually, starting in childhood or adulthood. Symptoms include lower limb and hip weakness causing waddling gait and frequent falls, progression may lead to dependency on wheelchairs and ventilators due to progressive muscular involvement.

DIAGNOSIS AND TESTING

Pompe disease is diagnosed through symptoms of muscle weakness and confirmed with additional tests. Diagnosis can be delayed due to symptom overlap with other conditions such as Spinal Muscular Atrophy and various muscular dystrophies.

Key diagnostic tests include:

– Blood tests to measure creatine phosphokinase (CPK) and transaminase levels.

– Blood tests to measure the enzymatic activity of acid alpha-glucosidase (GAA).

– Skin biopsy may be performed if blood tests are inconclusive, allowing for measurement of GAA activity in cultured skin cells.

– Electromyography

– Muscle biopsy under local anesthesia is indicated to rule out other muscle diseases and to make the diagnosis by looking for glycogen-filled lysosomes

– DNA genetic testing to identify mutations in the GAA gene responsible for the enzyme deficiency.

Diagnostic approaches may include neonatal screening to enable early treatment, especially for infants with the classic form of the disease. Prenatal testing through chorionic villus sampling and amniocentesis is also available.

HIGH-LEVEL EXPERTISE IN POMPE DISEASE

Pompe disease is a severe neuromuscular disorder in which the skeletal, respiratory and cardiac muscles deteriorate. It is a complex disorder that requires specific expertise. Centro Dino Ferrari (CDF) focuses on patients with Pompe disease and is one of the major centers in Italy with this specific expertise. CDF has been working on Pompe disease research for 40 years, has contributed to the development of the available treatments and has been treating patients for over 20 years. Meanwhile, to improve the patient’s future, the center is also working on improving current treatments and developing new treatments. Within the CDF, we work together structurally on scientific research, education and especially patient care. In addition, the Center works closely with other centers around the world, and it is member of the European Reference Networks (ERN) namely EURO-NMD.

TREATMENT

The primary treatment for Pompe disease is enzyme replacement therapy (ERT) with alglucosidase alfa (Myozyme), a lifelong regimen that alleviates symptoms and stabilizes or improves patient health. This therapy has shown significant benefits in survival rates among children with the classic form, primarily by enhancing heart function.

ERT is administered through intravenous infusions at our Center, with treatments varying in frequency between weekly for the classic form and biweekly for the non-classic form. Long-term patients may also receive home-based ERT under medical supervision.

Supportive treatments include physiotherapy, occupational therapy, speech therapy, nutritional support, management of cardiac symptoms and respiratory assistance. Research efforts to find a cure continue at both the Pompe Center and globally.

NEWS OF ENZYME THERAPY IN POMPE DISEASE

Several laboratories continue to make strides in developing recombinant enzymes to treat Pompe disease. Sanofi-Genzyme, known for pioneering enzyme replacement therapy with alglucosidase alfa, has developed a new enzyme called avalglucosidase alfa, also referred to as Nexviadyme. Amicus Therapeutics has taken a novel approach by combining a  new recombinant enzyme, cipaglucosidase alfa (marketed as Pombiliti), with a chaperone molecule, miglustat (known as Opfolda), as an enzyme stabilizer to minimize the inactivation of cipaglucosidase alfa in the circulation to enhance the treatment’s effectiveness. Research into gene therapy as a potential treatment for Pompe disease is also underway. For information on current clinical trials, contact us.

WHICH SPECIALIST WILL I BE IN CONTACT WITH?

In our Center, adults with Pompe disease are primarily treated by neurologists, while pediatricians and child neurologists oversee care for children. The treatment team also includes nurses, nurse specialists, dieticians, physiotherapists, psychologists, and social workers. Specialists such as ENT doctors for swallowing issues or pulmonologists for respiratory problems may be involved as needed. The main practitioner, who acts as a coordinator, maintains a comprehensive overview and monitors the patients’ ongoing treatment.

EXEMPTION CODE

Type 2 Glycogenosis: Code RCG060

What to do

To book FIRST LEVEL visits, contact the regional toll free call center:
Tel. 800638638

For SECOND LEVEL visits, with a specialised physician contact these numbers:
Tel. 0255038645
Tel. 0255038646

Before booking the visit, please make sure you have your physician’s (Specialists or GP) Health Service Authorization that specifically certifies a request for a visit to Neurologist.