Pompe disease is a rare, inherited disorder that causes the progressive weakening of muscles throughout the body. It is a type of lysosomal storage disorder caused by a mutation in the GAA gene, which produces the acid alpha-glucosidase (GAA) enzyme. Normally, GAA breaks down glycogen into glucose. However, a deficiency or lack of functional GAA leads to a toxic buildup of glycogen primarily in the heart and skeletal muscles. This accumulation damages muscle cells, and the severity of symptoms depends on the remaining enzyme activity and the age of onset.
Symptoms of Infantile-Onset Pompe Disease
Infantile-onset Pompe disease (IOPD) is the most severe form, typically presenting within the first few months of life. Infants experience profound, generalized muscle weakness, often described as hypotonia or “floppy baby syndrome.” This severe lack of muscle tone affects their ability to meet early developmental milestones, such as lifting their head or sitting up.
A defining and life-threatening feature of IOPD is significant cardiac involvement, specifically hypertrophic cardiomyopathy, where the heart muscle becomes abnormally thick and enlarged. Compromised heart function rapidly leads to heart failure. Historically, this, along with respiratory failure, caused death for most untreated babies before age two.
Affected infants also struggle with feeding due to muscle weakness in the face and tongue, leading to poor sucking and swallowing. This contributes to a failure to thrive, meaning they do not gain weight and grow as expected. Respiratory distress is common due to weakness in the diaphragm and breathing muscles, making them vulnerable to frequent lung infections.
Symptoms of Late-Onset Pompe Disease
Late-onset Pompe disease (LOPD) can manifest anytime from late childhood to adulthood. Symptoms are generally less severe and progress more slowly than the infantile form because individuals with LOPD retain some residual GAA enzyme activity. The most prominent feature is progressive skeletal muscle weakness, particularly affecting the limb-girdle muscles of the hips, shoulders, and trunk.
This muscle weakness causes difficulty with mobility tasks, such as climbing stairs, walking long distances, or getting up from a chair. Chronic fatigue and exercise intolerance are common complaints. The loss of muscle support around the spine can also lead to skeletal issues like scoliosis (sideways curvature) or lordosis (inward curvature of the lower back).
Respiratory compromise is a significant concern, stemming from weakness of the diaphragm and other chest muscles. Early signs can be subtle, including morning headaches, daytime sleepiness, or shortness of breath that worsens when lying down. Unlike the infantile form, the heart is typically spared from significant damage, though some patients may experience an enlarged heart or irregular rhythms.
How Symptoms Progress Over Time
Pompe disease is a progressive disorder, meaning symptoms steadily worsen over time as glycogen accumulates and damages muscle tissue. Even in late-onset cases, the loss of muscle function is continuous without therapeutic intervention. The rate of decline is much faster in the infantile form, where rapid deterioration of cardiac and respiratory function can be observed within months.
The most debilitating long-term consequence across both types is the decline of respiratory function, which is the primary cause of severe illness and death. Weakness of the diaphragm makes breathing increasingly difficult, particularly during sleep. This often necessitates the use of a mechanical ventilator, sometimes starting only at night.
As skeletal muscle weakness advances, it severely restricts mobility and independence, causing individuals to rely on various assistive devices. Patients frequently progress from needing a cane or walker to requiring a wheelchair. This weakness and fatigue significantly impact a person’s quality of life, underscoring the importance of early diagnosis and intervention to slow the disease’s trajectory.