Pompe disease [1 gene]

Pompe disease, or glycogenosis type II (MIM#232300), is a lysosomal storage disease characterized by glycogen storage, mainly in muscle tissue. It is caused by biallelic pathogenic variants in the GAA gene that lead to a deficiency in acid α-glucosidase activity.

This disease is divided into two subtypes: infantile onset and late onset. The infantile form is the most severe one and is characterized by an early onset (around 4 months of life on average) with hypotonia, generalized muscle weakness, feeding and growth impairment, hypertrophic cardiomyopathy, and respiratory distress. The late-onset form is characterized by slowly progressing proximal muscle weakness and respiratory failure, and debut can vary widely from childhood to late adulthood.

Patients affected with the infantile form of the disease present with hypotonia, generalized muscle weakness, feeding and growth impairment, hypertrophic cardiomyopathy, and respiratory distress.

Patients with the late-onset form of the disease present with progressive proximal muscle weakness mainly affecting the lower limbs. The reported manifestations mainly include fatigue and difficulty standing up, climbing stairs, and walking.

Its prevalence is estimated at 1 in 40,000 individuals in the European population.

Early detection of the disease is essential, as treatments consisting of enzyme replacement therapies are currently available and significantly improve patients’ quality of life, particularly when treatment is started early.