P.17.6 Globular inclusions are a frequent finding in infantile Pompe’s disease

Abstract

Pompe’s disease is a clinically and pathologically heterogeneous glycogen storage disease due to mutations in the a-glucosidase gene (GAA). It can be classified into infantile, childhood and adult onset forms. We describe the clinical and pathological spectrum in 4 patients with Pompe’s disease. The first patient presented in the first years of life with hypotonia and respiratory complications. The muscle features contained large vacuoles with increase glycogen and acid phosphatase activity. The second case presented at 13 months with proximal muscle weakness. His muscle biopsy showed small vacuoles in few fibres.Vacuolated fibres showed acid phosphatase activity and contained increased glycogen. These findings were confirmed with electron-microscopy. In addition we observed acid phosphatase positive globular inclusions. The third patient presented with mild hypotonia and hyperlaxity of proximal joints at the age of one. At this age muscle biopsy showed acid phosphatase positive/PAS negative inclusions as the main pathological sign in 3% of muscle fibres on average although it varied from one area to another of the section. In addition it showed small vacuoles in a few isolated fibers. There was some glycogen accumulation in some fibres although it did not always correspond to the vacuolated areas. The fourth case was asymptomatic apart from elevated CK levels which were detected on a routine analysis. His muscle biopsy did not show abnormalities at the light or ultrastructural levels. These data show that globular inclusions, previously only described in adults, can also be frequently observed in infantile Pompe’s patients and that they can be found by their own or in combination with vacuoles. The presence of these inclusions may be associated with the disease progression or with the specific mutations. Further studies are needed to elucidate the formation of these inclusions and how their relationship with a-glucosidase deficiency.