Postmortem Findings and Clinical Correlates in Individuals with Infantile-Onset Pompe Disease

Pompe disease (OMIM 232300), a glycogen storage disorder caused by deficiency in the lysosomal enzyme acid alpha-glucosidase (EC 3.2.1.20), results in weakness and cardiomyopathy in infants affected with the classic form. Although the primary disease manifestations are due to glycogen accumulation in skeletal and cardiac muscle, glycogen also accumulates in a variety of additional tissues. To improve our understanding of disease pathogenesis in long-term survivors, we reviewed postmortem results for three infants with the classic form of Pompe disease. We have observed a number of new complications in long-term survivors of infantile-onset Pompe disease, and we focused this postmortem study on pathological correlates. Findings in survivors include cardiac arrhythmias, which may be related to glycogen accumulation in cardiac conduction tissue; urinary incontinence, likely due to glycogen accumulation in smooth muscle; and refractory errors, possibly related to accumulation in ocular structures. These observations provide potential pathophysiologic correlates for complications in long-term survivors of infantile Pompe disease.