Adult glycogenosis type II (Pompe’s disease): morphological abnormalities in muscle and skin biopsies compared with acid alpha-glucosidase activity

Glycogen storage disease type II (GSD II) is an autosomal recessive deficiency of acid alpha-1,4-glucosidase (GAA) caused by mutations in the GAA gene located on human chromosome 17 (17q 25.2-q 25.3). Although its pathophysiology is partially understood, it has not yet been elucidated whether the level of GAA deficiency is directly proportional to the level of glycogen storage, vacuolar degeneration and/or GSD II severity. Muscle and skin biopsies were taken from three female patients with symptoms of progressive muscle weakness and respiratory failure: patient 1 aged 19, as well as patients 2 and 3 (two sisters) aged 31 and 29, respectively. Initial clinical manifestations, respiratory failure and muscle weakness, were similar in all the examined patients, while their character and intensity differed. For each examined patient, the activity of lysosomal GAA (at pH 3.8) was measured fluorometrically in isolated blood leukocytes (L) and dried blood spots (DBS). Biopsy samples were studied histologically, immunohistologically and ultrastructurally. Each of them displayed similar morphological features, although with different intensity. Muscle fibres were irregular in size with smaller non-rounded fibres and vacuolar degeneration. In vacuoles, we observed glycogen and intense positive ubiquitin reaction. Myofibrils were almost completely destroyed by the accumulation of glycogen granules in lysosomes and those free, without limiting membranes as well as by vacuoles of various size. Autophagic vacuoles were visible occasionally. Excess glycogen was also present in the walls of muscle and skin capillaries. All three patients showed reduced GAA activity ratios measured at pH 3.8 with and without acarbose (patient 1 – 0.12 in DBS and 0.07 in L; patient 2 – 0.05 in DBS and 0.07 in L; and patient 3 – 0.12 in DBS and 0.09 in L). Based on the study results, we concluded that GAA deficiency in vitro in late-onset type II glycogenosis was not directly proportional to the amount of glycogen storage, vacuolar degeneration and disease severity.