Overview of Pompe Disease
Diagnosing Pompe
Clinical ManifestationsDiagnosing Pompe
Given the wide range of clinical presentations for Pompe disease -- and the rarity of the disorder -- the clinical paths to diagnosis tend to vary tremendously.
Infants may present with:
- Muscle weakness
- Feeding difficulty
- Cardiomegaly
Late-onset patients (childhood, juvenile, and adult)
- Patients may initially complain of muscle weakness (primarily in the muscles of the trunk, lower limbs, and diaphragm) or respiratory distress
Physical findings in adults may be nonspecific and/or suggest more common myopathic disorders
- Symptoms can also include gait abnormalities, sleep apnea and fatigue, and delayed motor milestones (in children)
Differential diagnosis is especially difficult due to the wide range of symptoms commonly observed in other diseases and because many Pompe disease symptoms are highly variable across patients. As a result, the diagnosis of Pompe disease may first require the elimination of other possible causes.
While diagnosis is challenging, there are various methods to aid in narrowing down the diagnostic investigation from the clinical manifestations observed. Diagnostic workups, such as electromyography (EMG) or electrocardiography (ECG), may help further reveal the functional manifestation. More targeted tests, such as enzyme activity testing, may aid in definitive diagnosis of Pompe disease.
Regardless of what steps precede it, a conclusive diagnosis generally requires an enzyme assay test to demonstrate reduced or absent activity for the lysosomal enzyme acid alpha-glucosidase (GAA), using:
- Cultured skin fibroblasts
- Muscle biopsy
- Lymphocyte testing
- Dried blood spot testing (not yet available; under investigation in the United States)
For those who learn they are at risk for being a Pompe disease carrier during pregnancy, prenatal screening can determine whether an unborn child will be affected by the disease.
At present, no standardized diagnostic protocol has been universally adopted for Pompe disease. Consultation with specialists, such as geneticists, metabolic specialists, and neurologists who may be more familiar with the disease and who use qualified laboratories, may help to expedite the diagnosis.
