Contents
Introduction
Pompe disease, also called glycogen storage disease type II, is a genetically inherited condition caused by insufficient functioning of an enzyme called lysosomal acid alpha-1,4-glucosidase, or just acid alpha-glucosidase, due to a mutation of the GAA gene.
Autosomal recessive (AR) disorder caused by deficiency of the lysosomal enzyme acid-α-glucosidase (GAA), leading to generalized accumulation of lysosomal glycogen especially in the heart, skeletal and smooth muscle, and the nervous system.
- Only glycogen storage disease (GSD II) that is also a lysosomal storage disease (LSD)
History
The disease is named after Joannes Cassianus Pompe, who characterized it in 1932. Pompe described accumulation of glycogen in muscle tissue in some cases of a previously unknown disorder. This accumulation was difficult to explain as the enzymes involved in the usual metabolism of glucose and glycogen were all present and functioning.
The basis for the disease remained a puzzle until Christian de Duve’s discovery of lysosomes in 1955 for which he won the Nobel Prize in 1974. His co-worker Henri G. Hers realised in 1965 that the deficiency of a lysosomal enzyme (α-glucosidase) for the breakdown of glycogen could explain the symptoms of Pompe disease. This discovery led to establishing the concept of lysosomal storage diseases, of which 49 have been described (to date).
Classification
Glycogen storage diseases (GSD):
Inherited metabolic disorders of glycogen metabolism


Pompe’s disease:
- Infantile-onset PD (IOPD): Onset before 12 months with cardiomyopathy (Classic Pompe disease: ) or without cardiomyopathy (Non-classic Pompe disease)
- Late-onset PD (LOPD): Onset after 12 months with cardiomyopathy (childhood, juvenile and adult-onset)
Clinical features
IOPD typical presentation:
- Hypotonia (52-96% cases)
- Progressive weakness
- Macroglossia (29-62% cases)
- Hepatomegaly (29-90% cases)
- Cardiac involvement:
- Left ventricular hypertrophy (83-100% cases)
- Cardiomegaly (92-100% cases)
- Hypertrophic cardiomyopathy (88% cases)
- Murmur (46-75% cases)
- Respiratory distress (41-78% cases)

LOPD presentation:
- Slowly progressive limb-girdle type weakness (95% cases)
- Respiratory insufficiency without significant cardiomyopathy
- Cardiac involvement:
- Wolff-Parkinson-White syndrome
- Left ventricular hypertrophy
- Dilatation of ascending aorta
- Rigid spine syndrome (progressive limitation of the neck and trunk)
- Scoliosis
- Low body weight
Diagnosis
- Muscle biopsies
- GAA mutation analysis
- GAA enzyme activity of muscle, skin fibroblasts, amniocytes
- Dried blood spots (DBS)

Management
- Alglucosidase alfa (Myozyme) (recombinant enzyme)