Pompe disease is a rare genetic disorder impacting the body’s ability to break down glycogen. This leads to glycogen accumulation within cells, especially muscle tissues. While it can manifest at any age, its presentation in adults, known as late-onset Pompe disease, involves progressive weakening of muscles and other systems.
The Underlying Cause
Pompe disease stems from a genetic alteration in the GAA gene, located on chromosome 17. This gene provides instructions for producing an enzyme called acid alpha-glucosidase (GAA). The GAA enzyme normally resides within lysosomes, cellular compartments responsible for breaking down substances, including glycogen.
When mutations occur in the GAA gene, the body produces a reduced amount of functional GAA enzyme or none at all. Glycogen then accumulates within the lysosomes, disrupting normal cellular function, particularly in muscle cells, and leading to tissue damage.
Pompe disease is inherited in an autosomal recessive pattern, meaning an individual must inherit two copies of the mutated GAA gene, one from each parent. Infantile-onset Pompe disease involves a complete or near-complete absence of the GAA enzyme and manifests in the first few months of life. Late-onset Pompe disease (LOPD), which affects adults, is characterized by lower levels of GAA enzyme activity.
How Pompe Disease Affects Adults
Late-onset Pompe disease (LOPD) in adults presents with varied symptoms. Muscle weakness is a prominent feature, often beginning in muscles closest to the body’s core, such as the hips, legs, shoulders, and torso. This leads to difficulty with activities like walking, climbing stairs, lifting objects, and performing daily tasks.
Respiratory issues are common in LOPD due to weakening of breathing muscles, particularly the diaphragm. Individuals may experience shortness of breath, especially with exertion, frequent respiratory infections, and morning headaches. Sleep apnea, where breathing repeatedly stops and starts during sleep, can also occur.
Adults with Pompe disease may also experience generalized muscle pain, fatigue, and unintended weight loss. While cardiac involvement is less common and less severe in LOPD compared to infantile-onset forms, some individuals may develop an irregular heartbeat. The progression of symptoms in LOPD is slower than in infantile forms, but it can still lead to significant disability over time.
Diagnosing Pompe Disease in Adults
Diagnosis of Pompe disease in adults often begins with suspicion based on characteristic clinical symptoms, such as unexplained progressive muscle weakness and respiratory difficulties. Since symptoms can be vague and overlap with other neuromuscular conditions, a thorough medical history and physical examination are important.
Once suspected, specific laboratory tests confirm the diagnosis. A primary test measures the activity of the acid alpha-glucosidase (GAA) enzyme. This can be done using a dried blood spot test or through a muscle biopsy. A significantly reduced or absent GAA enzyme activity level indicates Pompe disease.
Genetic testing also identifies mutations in the GAA gene, providing definitive confirmation. Identifying specific genetic mutations can offer insights into the likely progression and severity of the disease. The combination of clinical suspicion, enzyme activity measurement, and genetic testing helps diagnose Pompe disease in adults.
Managing Pompe Disease
The primary treatment for Pompe disease in adults is Enzyme Replacement Therapy (ERT). This therapy involves intravenously administering a manufactured version of the acid alpha-glucosidase (GAA) enzyme, which the body lacks. The goal of ERT is to replenish the deficient enzyme, allowing for the breakdown of accumulated glycogen in cells, reducing muscle damage, and slowing disease progression. ERT infusions are typically given every two weeks.
Supportive care plays a key role in managing Pompe disease in adults. Physical therapy is often recommended to maintain muscle strength, improve mobility, and manage pain. Respiratory support, such as non-invasive ventilation, may be necessary to assist breathing, especially during sleep. Devices like cough assist machines can also help clear airways.
Nutritional counseling is also important, ensuring individuals receive adequate nutrients to support muscle health. A multidisciplinary healthcare team, including neurologists, metabolic specialists, cardiologists, respiratory specialists, physiotherapists, and dietitians, provides comprehensive care for individuals living with Pompe disease.