Progress in Enzyme Replacement Therapy in Glycogen Storage Disease Type II

Abstract

Glycogen storage disease type II (GSDII) is an autosomal recessive lysosomal disorder caused by mutations in the gene encoding alpha-glucosidase (GAA). The disease can be clinically classified into three types: a severe infantile form, a juvenile and an adultonset form. Cases with juvenile or adult onset GSDII mimic limb-girdle muscular dystrophy or polymyositis and are often characterized by respiratory involvement. GSDII patients are diagnosed by biochemical assay and by molecular characterization of the GAA gene. Ascertaining a natural history of patients with heterogeneous late-onset GSDII is useful for evaluating their progressive functional disability. A significant decline is observed over the years in skeletal and respiratory muscle function. Enzyme replacement therapy (ERT) has provided encouraging results in the infantile form. It is not yet known if ERT is effective in late-onset GSDII. We examined a series of 11 patients before and after ERT evaluating muscle strength by MRC, timed and graded functional tests, 6-minute walk test (6MWT), respiratory function by spirometric parameters and quality of life. We observed a partial improvement during a prolonged follow-up from 3 to 18 months. The use of different clinical parameters in the proposed protocol seems crucial to determine the efficacy of ERT, since not all late-onset patients respond similarly to ERT.

Keywords: glycogen storage disease type II; protocol; trial.

Figure 1.

Patient 8, a 50-year-old woman, trying to raise from a chair (A) using both hands on the table or one hand on her thigh (B).

Figure 2.

Muscle biopsies from patients with GSDII might show evident fibre vacuolization (panel A, patient 7) or few atrophic fibres or central nuclei but nonevident vacuoles (panel B, patient 8). Hematoxylin and eosin stain. Microscope magnification x400.

Figure 3.

6MWT of 11 patients treated with ERT for 3 to 18 months. T₀ indicates initial treatment. Patient 8 stopped treatment for adverse reaction. Normal range of healthy controls = 400-700 m. Two patients were unable to walk.

Figure 4.

Time to complete functional performances in GSGC score of patient 7. T₀ indicates initial treatment. The patient fell accidentally after 10 months of therapy and was subsequently unable to raise from bed for 1 month. At the last examination her motor function was still affected by the month of forced immobility.

Figure 5.

Forced vital capacity (FVC) in sitting position in 11 patients treated with ERT for 3 to 18 months. T₀ indicates initial treatment.

Figure 6.

SF-36 scale in two treated patients before and after ERT. PF, physical functioning; RP, role physical; BP, bodily pain; GH, general health; VT, vitality; SF, social functioning; RE, role emotional; MH, mental health.