Differential diagnosis and misdiagnosis of Pompe disease in adults

Abstract

Traditionally, Pompe disease has been defined as a storage disease, which is reflected in the synonyms glycogen storage disease type II and glycogenosis type II used for this rare autosomal recessive condition. The definition was based on the discovery of accumulation in tissue samples, particularly in skeletal muscle, of the first characterized patients.! For these historical reasons, the diagnosis of Pompe disease in a patient with limb-girdle weakness was generally only considered when accumulation was noted in the muscle biopsy. With improved diagnostic tests based on mutation analysis and the assessment of enzymatic activity of acid a-glucosidase (GAA), it became obvious that accumulation and autophagic vacuoles in skeletal muscle, previously assumed to be pathological hallmarks of the disease, were not essential for the diagnosis of Pompe disease.s In recent years, the spectrum of muscle biopsy findings in adults with Pompe disease has been extended from mild myopathic changes to dystrophic and even neurogenic changes, with and without accumulation and vacuoles. It is clear that there are no pathognomonic changes common to all biopsies; pathology depends on the age of the patient, the severity of the disease, and the site of the muscle biopsy. Improved diagnostic tests have similarly illustrated that the spectrum of clinical presentations is also much broader than was originally assumed and that muscle weakness, a very nonspecific symptom, is the most common complaint in adult patients.l As the spectrum of clinical and pathological findings in adult Pompe patients became broader, new diseases were characterized that shared some of the more characteristic clinical and pathological findings of Pompe disease. There are a number of diseases, including the limb-girdle muscular dystrophies and myofibrillar myopathies, that show limb-girdle weakness, respiratory distress, and vacuoles in skeletal muscle biopsies and thus make the differential diagnosis of Pompe disease more challenging. As a result of this diagnostic challenge, the diagnostic algorithm for adult Pompe disease should include an easy-to-use and highly specific and sensitive screening test for the condition, such as the currently available dried blood spot test that measures GAA activity, With better treatment options available, all patients with Pompe disease deserve an accurate diagnosis.