“I'm fine; I'm just waiting for my disease” The new and growing class of presymptomatic patients

This issue of Neurology ® contains a case report1 describing a young man with Pompe disease, a lysosomal/glycogen storage disorder caused by deficiency of the acid α-glucosidase enzyme (GAA). As a clinical case, it provides a prospective history of the early and asymptomatic years of a patient with late-onset Pompe disease. The patient described is also emblematic of a new trend that neurologists, medical geneticists, and other clinicians are facing in patient diagnosis—that is, the presymptomatic diagnosis of a serious and progressive disorder in an individual who is currently healthy. When Pompe disease presents in infancy, the classic form results in cardiomyopathy, hypotonia, and respiratory insufficiency leading to death, usually before 12 months. Enzyme replacement therapy (ERT) has been available for these infants since 2006, and early initiation can improve cardiac and motor function in a subset of affected patients, allowing these children to survive what previously had been a fatal disease. Later-onset forms of Pompe disease are generally restricted to skeletal and respiratory muscles with slow progression, but also with potential early death. In these patients, ERT can further slow disease progression but the benefits appear to be less dramatic than those observed in some infants. ERT is exceedingly expensive and must be continued lifelong, at least until alternative treatments are developed. In this report, a serendipitous and early …