Pompe disease is a rare, inherited neuromuscular disorder belonging to the group of lysosomal storage disorders. It is caused by a deficiency in the acid alpha-glucosidase (GAA) enzyme, which normally breaks down glycogen within the cells’ lysosomes. When the GAA enzyme is missing or not working correctly, glycogen builds up to toxic levels, primarily affecting muscle cells throughout the body. This accumulation damages muscle architecture, leading to progressive weakness and wasting.
Symptoms of Infantile-Onset Pompe Disease
Infantile-onset Pompe disease (IOPD) is the most severe and rapidly progressing form of the disorder, typically presenting symptoms within the first few months of life. Affected infants have little to no functional GAA enzyme activity, leading to a swift accumulation of glycogen in the heart and skeletal muscles. A defining early sign is profound muscle weakness, often described as hypotonia or “floppy baby syndrome,” characterized by poor muscle tone and difficulty holding up the head.
The most life-threatening feature of IOPD is severe cardiac involvement, specifically hypertrophic cardiomyopathy, which causes the heart muscle to become abnormally enlarged and thickened. This progressive heart damage often leads to heart failure and is the primary cause of mortality in untreated infants, usually occurring before age two. Respiratory distress is also a serious symptom due to the weakening of breathing muscles.
Infants with this form of Pompe disease frequently struggle with poor feeding and difficulty swallowing, resulting from muscle weakness in the face and tongue. These feeding difficulties contribute to a failure to thrive, causing the baby to struggle to gain weight and grow. Motor skill development is also significantly delayed, with children failing to reach milestones such as rolling over or sitting up.
Other manifestations include an enlarged liver (hepatomegaly) and an enlarged tongue (macroglossia). The rapid onset of severe symptoms, particularly the combination of generalized muscle weakness and progressive heart failure, distinguishes the infantile form from the later-onset counterpart.
Symptoms of Late-Onset Pompe Disease
Late-onset Pompe disease (LOPD) can manifest anytime from childhood to adulthood, characterized by a milder presentation and slower progression than the infantile form. Individuals with LOPD retain some residual GAA enzyme activity, which accounts for the variable and less severe symptom profile. The primary symptom is progressive skeletal muscle weakness, often beginning in the muscles closest to the body’s core, such as the hips, shoulders, and trunk.
This weakness causes increasing difficulty with daily mobility, such as climbing stairs, rising from a chair, or walking long distances. Patients may develop a waddling or swaying gait and report frequent trips and falls. Unlike the infantile form, significant cardiac involvement is typically absent, though some individuals may experience an enlarged heart or minor rhythm disturbances.
Respiratory compromise is a major concern and often the most life-threatening symptom in LOPD, resulting from weakness in the diaphragm and other breathing muscles. Patients may experience shortness of breath during exertion, recurrent respiratory infections, and difficulty breathing while lying flat. Diaphragm weakness can also lead to sleep-disordered breathing, manifesting as morning headaches, daytime sleepiness, and fragmented sleep.
Other common, though less prominent, symptoms include chronic muscle pain, fatigue, and exercise intolerance. The progressive muscle weakness can also lead to secondary skeletal issues, such as scoliosis (a sideways curvature of the spine) and contractures. Because the symptoms are often generalized and progressive, LOPD is sometimes initially misdiagnosed as other forms of muscular dystrophy.
Progression and Functional Impact of Symptoms
The progression of Pompe disease symptoms directly correlates with the age of onset, with earlier presentation indicating a faster and more severe trajectory. In the infantile form, the rapid accumulation of glycogen leads to profound muscle damage and organ dysfunction in a matter of months. Untreated infants face rapid functional decline, with cardiorespiratory failure typically occurring within the first year of life.
For those with LOPD, the functional impact is slower but cumulative, progressively eroding independence and quality of life. The increasing weakness in the legs and trunk eventually impairs ambulation, with many individuals requiring mobility aids like canes, walkers, or wheelchairs over time. Respiratory muscle weakness eventually necessitates chronic ventilatory support, such as a BiPAP or CPAP machine, particularly for breathing assistance during sleep.
The chronic muscle deterioration also affects posture and causes secondary issues like lower back pain and joint stiffness. The cumulative effect of muscle weakness, chronic pain, and respiratory insufficiency contributes significantly to pervasive fatigue, limiting the ability to perform daily activities. The functional outcome depends heavily on the extent of muscle damage and timely treatment initiation.