Hypertrophic cardiomyopathy in pompe disease is not limited to the classic infantile-onset phenotype.

Abstract

Pompe disease is a genetic disorder caused by a deficiency of acid α-glucosidase (GAA). Patients with classic infantile-onset Pompe disease usually present with hypertrophic cardiomyopathy and die before 1 year of age, if not treated with enzyme replacement therapy (ERT). In comparison, patients with late-onset Pompe disease typically do not have hypertrophic cardiomyopathy. However, here we describe five patients who presented with hypertrophic cardiomyopathy but did not fit the criteria of classic infantile-onset Pompe disease. Their ages at diagnosis of cardiomyopathy were 1 month in two patients following detection of an audible cardiac murmur and 2-3 years in the three remaining patients. All patients survived for 5-8 years without ERT. Three patients died before the advent of ERT from causes other than congestive heart failure. One patient had a good response to ERT starting at 5 years of age. The sibling of one patient, who did not receive ERT and died at age seven, was diagnosed prenatally. At 3months of age, the sibling had hypertrophic cardiomyopathy, and a muscle biopsy at that time revealed glycogen accumulation.This case series demonstrates that Pompe disease is a continuum of disease, and the development of cardiomyopathy is not limited to classic infantile-onset Pompe disease. These patients do not fit into the discrete phenotypes of infantile- or late-onset Pompe disease, which may suggest reconsidering the nomenclature of Pompe disease.