HEART AND MUSCLE HEALTH IN FOCUS: POMPE DISEASE’S UNIQUE CHALLENGES

Medically Reviewed by Dr. Sony Sherpa, (MBBS) - August 19, 2024

Pompe disease is a rare genetic disorder affecting the muscles and heart.

The disorder arises due to genetic mutations affecting the GAA gene, which is responsible for encoding the enzyme acid alpha-glucosidase (GAA). This enzyme is responsible for breaking down glycogen, a complex sugar that is stored in the cells, especially in the muscles and heart.

When the Pompe disease enzyme is missing or not working properly, glycogen accumulates in the cells and damages them. This leads to progressive muscle weakness and heart problems, which are the main defining symptoms of the disease.

Other names for Pompe disease include acid alpha-glucosidase deficiency and glycogen storage disease type II.

Types and Symptoms of Pompe Disease

Pompe disease can be classified into two main types based on the age of onset and the severity of symptoms: infantile-onset and late-onset.^[1]

Infantile-onset Pompe Disease

Infantile-onset Pompe disease is the severest form of the disorder. It occurs when there is little or no GAA enzyme activity. Symptoms usually appear within the first year of life, often around 4 months of age. They include:

• Feeding problems and poor weight gain
• Trouble breathing and frequent respiratory infections
• Muscle weakness and floppiness
• Enlarged heart (cardiomegaly) and heart failure
• Enlarged liver (hepatomegaly) and liver dysfunction
• Enlarged tongue (macroglossia) and difficulty swallowing
• Head lag and developmental delay

Without treatment, most infants with Pompe disease die from cardiac or respiratory failure within a year. Newborn screening for Pompe disease is essential for avoiding early mortality.

Late-onset Pompe Disease

Late-onset Pompe disease is a milder form of the disorder. Unlike in early-onset Pompe disease, there is still some residual GAA enzyme activity in the late-onset type. This accounts for Pompe disease symptoms in adults, although the symptoms can appear at any age, from childhood to adulthood. Earlier onset indicates a faster disease progression with more severe symptoms and a worse prognosis.

Symptoms include:^[2]

• Muscle weakness and pain, especially in the legs and trunk
• Difficulty walking, climbing stairs, and rising from a chair
• Breathing problems, especially during sleep (sleep apnea)
• Reduced lung function and respiratory failure
• Scoliosis (curvature of the spine) and osteoporosis (bone loss)
• Hearing loss and speech problems
• Fatigue and exercise intolerance

The progression and severity of late-onset Pompe disease varies from person to person. Some people may have a slow decline in their muscle function, while others may experience rapid deterioration. The heart is usually not affected by late-onset Pompe disease, but some people may develop arrhythmias (irregular heartbeats) or cardiomyopathy (heart muscle disease).

Diagnosis and Treatment of Pompe Disease

Pompe disease can be diagnosed by measuring the GAA enzyme activity in blood, skin, or muscle samples. Genetic testing can also confirm the diagnosis by identifying the mutations in the GAA gene.

Enzyme Replacement Therapy

The main treatment for Pompe disease is enzyme replacement therapy (ERT), which involves infusing synthetic GAA enzyme into the bloodstream. This Pompe disease treatment can help reduce glycogen accumulation in the cells, improve muscle function, and prolong survival. According to some sources, Pompe disease life expectancy with treatment is five times higher on average.^[3]

ERT is available for both infantile-onset and late-onset Pompe disease, consisting of Lumizyme (Myozyme) for adults and avalglucosidase alfa-ngpt (Nexviazyme) for infants.

Supportive Therapies

Aside from enzyme replacement, treatment for Pompe disease is often complex and depends on the symptoms and their severity. Patients tend to require a multidisciplinary team of specialists, including neurologists, cardiologists, pediatricians, physical therapists, and others.

Supportive treatments for Pompe disease may include:

• Respiratory therapy to help with breathing problems
• Physical therapy to maintain muscle strength and mobility
• Occupational therapy to assist with daily activities
• Speech therapy to improve communication skills
• Nutritional support to ensure adequate growth and development
• Cardiac medications to manage heart problems
• Pain medications to relieve muscle pain
• Bone medications to prevent osteoporosis

Prevention and Outlook for Pompe Disease

Pompe disease is an inherited disorder that follows an autosomal recessive pattern. This means that both parents must carry a mutated copy of the GAA gene for a child to inherit it. Each child of such parents has a 25% probability of inheriting two mutated copies of the gene and developing Pompe disease, a 50% chance of inheriting one mutated copy of the gene and being a carrier, and a 25% chance of inheriting two normal copies of the gene and being unaffected.

Genetic counseling can help people who have a family history of Pompe disease or who are carriers of the GAA gene mutation to understand their risk of having a child with Pompe disease. Prenatal testing can also detect Pompe disease in an unborn baby by analyzing cells from amniocentesis or chorionic villus sampling. Newborn screening for Pompe disease can identify babies with Pompe disease shortly after birth by measuring GAA enzyme activity in blood samples.

In some countries and states, newborn screening for Pompe disease is mandatory.^[4] Due to the large number of genetic variations seen in Pompe disease, the severity and prognosis of the disease may be overlooked in some patients carrying unknown mutations of the GAA gene.

The outlook for people with Pompe disease depends on several factors, such as the type and severity of symptoms, the age of onset, the treatment response, and the occurrence of complications. Early diagnosis and treatment can improve the quality of life and extend lifespan.

Conclusion

Pompe disease is a rare hereditary disorder that affects the muscles and heart due to mutations in the GAA gene. It can cause various symptoms depending on the age of onset and the severity of the condition. The main treatment is enzyme replacement therapy, which can improve the symptoms and prolong the survival of people with Pompe disease. Genetic counseling, prenatal testing, and newborn screening can help prevent and diagnose Pompe disease early. People with Pompe disease can live better lives with proper medical care and support.

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