Infantile acid maltase deficiency

Summary

The loss of normal ultrastructure of skeletal muscle during the relentless course of infantile acid maltase deficiency (AMD) is re-examined in the light of the lysosomal rupture hypothesis. This hypothesis suggests that movement and increased myofibril rigidity during contraction cause lysosomes in muscle to rupture and release glycogen and other lysosomal contents to a much greater extent than do lysosomes in other cell types in cases of infantile AMD. Muscle fibers are destroyed, while macrophages and other cells mostly accumulate glycogen in storage lysosomes without being destroyed. When morphological stages of fiber destruction are placed in a sequential series, from fibers most like normal infant muscle to those with only remnants of muscle ultrastructure, the earliest stages seen contain intact storage lysosomes. Intermediate stages exhibit ruptured lysosomal membranes and free glycogen as well as glycogen in lysosomes. Loss of myofibrillar material and loss of glycogen occur in later stages of fiber destruction.

Membrane-enclosed glycogen and mitochondria are relatively protected from the process of destruction. The electron-microscopic observations support the lysosomal rupture hypothesis and are compatible with the original proposal of Hers, that the disease results from a deficiency of a single lysosomal enzyme. Secondary changes other than muscle fiber destruction probably relate to disrupted control mechanisms and the nature of muscle as a specialized cell. At least two different mechanisms could contribute to the loss of contractile activity and myofibrillar structure.