Pompe disease (or glycogenosis type II) is an autosomal recessive inherited disease and belongs to the group of lysosomal glycogen storage diseases. A reduced activity of the enzyme 1,4-α-glucosidase (GAA, acid maltase) leads to a dysfunction of glycogen degradation in the lysosomes. The disease is caused by pathogenic variants in the GAA gene.
The enzyme defect leads to a progressive systemic accumulation of glycogen in the lysosomes. Heart cells and type II muscle cells are predominantly affected. Pompe disease is classified into two forms based on the occurrence of the first symptoms of the disease:
- In the infantile course, there is a homogeneous clinical picture with marked muscle weakness ("floppy infants"), respiratory insufficiency and developmental delay. If untreated, most children die of heart failure within the first year of life.
- In the late-onset form with a highly variable course, differentiation from other muscle diseases is difficult. Symptoms may include progressive muscle weakness, especially of the muscles close to the trunk, back pain, scoliosis, dyspnea, sleep apnea, morning headaches, and daytime fatigue.
Molecular genetic testing of the GAA gene should be performed before enzyme activity determination of 1,4-α-glucosidase. The disease is inherited in an autosomal recessive pattern, meaning that both alleles must be affected for the enzyme deficiency to manifest clinically. It is a rare disease with a worldwide prevalence of approximately 1:40,000. In addition to symptomatic treatment, enzyme replacement therapy has been available in Europe since 2006.
Tarnopolsky et al. 2016, Can J Neurol Sci 43:472-85 / ACMG Practice Guideline, Wang et al. 2011, Genetics In Medicine 13:457 / Parkinson-Lawrence et al. 2010, Physiology, 25:102 / Schoser 2007, Akt Neurol 34:283 / ACMG Practice Guideline, Kishnani et al. 2006, Genetics IN Medicine 8:267 / Vellodi 2004, Brit J of Haematology, 128:413