Infantile acid maltase deficiency

Summary

Infantile acid maltase deficiency (Pompe’s disease, glycogenosis II) is a progressive, severe lysosomal storage disease in which skeletal and cardiac muscle fibers accumulate membrane-bound and free glycogen and are destroyed. New information in this report concerns 1) early hypertrophy of skeletal muscle fibers, 2) absence of size change as glycogen is lost, and 3) the ultrastructure of end-stage fibers empty of glycogen. Muscle fibers enlarge as they accumulate glycogen and then stay large as glycogen is lost. They are so large that, if empty fibers did in fact contain glycogen, over 80% of the muscle would be glycogen instead of 6.3–11.5% (from 37 published determinations). Fibers that have reached “empty” end-stage are shown to be more numerous than all other stages combined in biopsies from infantile acid maltase deficiency. Ultrastructurally, end-stage fibers contain much “empty” space (liquid-filled without fine structure) and various remnants and masses of altered myofibrillar and sarcoplasmic material. Many broken membranes originally enclosing glycogen in storage lysosomes are seen. A single broken membrane can enclose an area larger than the cross section area of a muscle fiber from a normal infant. The results support the proposal of Hers that the disease is due to a deficiency of the single lysosomal enzyme acid maltase. The results also support the lysosomal rupture hypothesis of Griffin, which accounts for muscle fibers being more damaged than are other cells and for the release of glycogen to the sarcoplasm.