Diagnosis

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, and/or cardiomegaly while older patients may initially complain of muscle weakness or respiratory distress.

The physical findings in adults may be particularly non-specific and/or suggest more common myopathic disorders. 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 level testing, may aid in definitive diagnosis of Pompe disease.

Regardless of what steps precede it, a conclusive diagnosis generally requires that a biopsy of cultured skin fibroblasts or muscle tissue demonstrate reduced or absent activity for the lysosomal enzyme acid alpha-glucosidase (GAA). For those who learn they are at risk of 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, neurologists, or endocrinologists who may be more familiar with the disease and who use qualified laboratories may help to expedite the diagnosis.