What is the hallmark feature of Pompe disease in infants?

• A. Progressive muscle weakness with pes cavus
• B. Distal weakness with foot drop
• C. Hypertonia with spasticity
• D. Hypotonia with hypertrophic cardiomyopathy and poor respiratory effort

Answer: (D)

Infantile Pompe disease is defined by early, severe generalized muscle weakness (hypotonia) and prominent heart involvement due to glycogen buildup in muscle cells. The enzyme deficiency—acid alpha-glucosidase—causes lysosomal glycogen accumulation, with the heart being particularly affected. In infants, this leads to hypertrophic cardiomyopathy, which thickens the heart walls and impairs function, contributing to poor cardiac output and respiratory effort. The combination of floppy (hypotonic) muscles and a failing, thickened heart often results in difficult or poor respiratory effort early in life. This distinctive trio—hypotonia with hypertrophic cardiomyopathy and respiratory weakness—defines the infantile presentation.

Other patterns don’t fit as well: hypertonia with spasticity points toward upper motor neuron or central causes; distal weakness with foot drop suggests a neuropathic or distal myopathy pattern; and weakness with pes cavus can appear in several neuromuscular disorders but does not capture the hallmark heart involvement seen in infantile Pompe.