[LS6-2B-2] Pompe disease – How can we make a diagnosis?
Pompe disease is caused by primary deficiency of acid α-glucosidase (GAA), the glycogen degrading enzyme in lysosome, which results in the accumulation of glycogen in autophagic vacuoles. The diagnosis should not be missed especially because the enzyme replacement therapy has been proven to be efficacious. Infantile form of Pompe disease is characterized clinically by hypertrophic cardiomyopathy and muscle hypotonia/weakness, in addition to occasional hepatomegaly and tongue hypertrophy, and pathologically by autophagic vacuoles with glycogen accumulation. With this unique clinicopathological presentations, it is usually not difficult to reach the diagnosis in this form. In late-onset form, however, often patients show only unspecific proximal myopathy. Even on muscle pathology, typical vacuoles are sometimes not included in the section especially in adult-onset cases, which makes the diagnosis difficult to make. We have found that a unique global cytoplasmic inclusion with acid phosphatase activity on muscle pathology seem to be a sensitive and specific marker especially in adult cases. In Japan, more than 70% of muscle biopsy cases are diagnosed in our laboratory. Therefore, it is our responsibility that we should not overlook any case. Therefore, more recently, we started GAA activity screening using muscle sections for all muscle biopsy cases we receive, in collaboration with Kumamoto University. Fortunately, so far, we have not found any patient, suggesting that the prevalence of the disease is much lower than other regions such as Taiwan, China and Netherlands.