Infantile acid maltase deficiency

Abstract

In infantile acid maltase deficiency (AMD), masses of glycogen accumulate in muscle fibers and are then gradually digested. The metachromatic material found in some glycogen-filled fibers, not previously studied with the electron microscope, has two different fine structural appearances. Some is similar in shape and size to glycogen beta granules, but is more intensely stained, and some is in larger granules, irregular in shape, and has even higher stain affinity. Since acid maltase deficiency was identified by Hers, others have proposed that more than one genetic defect or additional extralysosomal factors are required to account for massive glycogen accumulation and metachromasia. There is no direct evidence of additional rare genetic defects. Presented herein are two simple proposals consistent with the primary deficiency. The first is that some partly digested glycogen is condensed and that this concentrates the sites that bind dye, producing metachromasia and other differences from normal glycogen. The second is that the massive accumulation of glycogen in muscle fibers involves, in addition to previously recognized lysosomal storage and lysosomal rupture, inactivation of sarcoplasmic phosphorylase caused by disruption of excitation-contraction linkages. These two proposals are physiologically plausible and potentially testable and do not invoke the coincidence of two or more rare genetic mutations.