Pompe disease, also known as glycogen storage disease type II (GSDII), is an autosomal recessive genetic disorder that progressively causes weakness in the heart and skeletal muscles.¹ This disorder is caused by mutations in the gene responsible for producing an enzyme called acid alpha-glucosidase (GAA) which breaks down glycogen. These mutations cause a deficiency in this enzyme and result in the accumulation of glycogen in the lysosomes and cytoplasm of cells.¹ Understanding the different types of Pompe disease is important for seeking accurate diagnosis, treatment and management. 

Classifications of Pompe Disease

There are two types of Pompe disease: Infactile-Onset Pompe Disease (IOPD) and Late-Onset Pompe Disease (LOPD).¹ Different symptoms occur in each of these types, which follow a distinct progression pathway.

Infancy-onset Pompe Disease (IOPD)

Infantile onset Pompe disease (IOPD) is present in the first few months of life and progresses rapidly. This is because there are little to no enzymes present.² Within the first couple of months, there will be signs of muscular damage to the heart which can cause hypertrophic cardiomyopathy³ (enlargement of heart muscle cells, causing the walls of the heart to thicken). IOPD can also cause respiratory failure due to the weakness of the skeletal muscles affecting the diaphragm. 

To diagnose IOPD, the GAA enzyme activity needs to be measured through genetic testing, to indicate any gene mutations present and to observe the glycogen accumulating in tissues with a muscle biopsy.⁴ 

A method of treatment for Pompe disease is enzyme replacement therapy (ERT),⁵ which improves muscle tone and decreases glycogen storage. This procedure is done by inserting doses of alpha-glucosidase directly into the bloodstream to break down the glycogen in the cells, which helps prevent the buildup.⁶ 

Late-onset Pompe Disease (LOPD)

Late-onset Pompe disease, also known as juvenile or adult-onset Pompe disease, can start at any age from childhood to adulthood and usually progresses slowly. Symptoms can include proximal muscle weakness in the shoulders and hips, or breathing difficulties due to weakness of the intercostal muscles and the diaphragm.² 

There are different methods available to diagnose LOPD. This can include gene sequencing to assess the GAA gene, a creatine kinase⁷ blood test to check for signs of any muscular damage present, or using electron microscopy of muscle biopsy.² MRI (magnetic resonance imaging⁸), is another diagnostic tool for analysing skeletal muscles.⁹ To help diagnose muscular disorders, T1w imaging is used to recognise the patterns of fat infiltration and uses the 3-point Dixon to calculate the percentage of muscle fat and changes that occurred over time.⁹ 

Enzyme replacement therapy (ERT) is used to treat adult-onset Pompe disease by using Alglucosidase alpha¹⁰ (acid alpha-glucosidase). to remove the accumulated glycogen from the lysosomes .² Physical and occupational therapy, the placement of a feeding tube, and mechanical ventilation are supportive therapy methods used for individuals who have LOPD.^1,2

Signs and symptoms of Pompe disease

Infantile-onset Pompe disease in newborns can lead to symptoms such as:⁵ 

• Poor weight gain
• Breathing trouble
• Respiratory failure
• Muscle weakness
• Feeding problems

Adult-onset Pompe disease shows different symptoms such as:¹³

• Lack of appetite
• Hearing loss
• Increased levels of creatine kinase
• Weight loss

Related Conditions

Duchenne Muscular Dystrophy (DMD)

Duchenne muscular dystrophy (DMD) is a neuromuscular genetic disorder caused by a gene mutation in the protein dystrophin.¹¹ This condition is an X-linked recessive disorder, meaning it is located on the X chromosome of the sex chromosomes.¹² 

Becker Muscular Dystrophy (BMD)

Becker muscular dystrophy (BMD) is an inherited condition causing muscle weakness and degeneration due to the presence of a gene mutation. It most commonly affects males due to the X-linked chromosome (passed down directly from the mother who is a carrier).¹⁴ 

FAQ’s

Is there a cure for Pompe disease?

ERT has been shown to increase the life expectancy of patients suffering from infantile-onset Pompe disease. However, the disease does not currently have any cure.² 

How rare is Pompe disease?

Pompe disease affects 1 in 40,000 people in countries such as the United States, Taiwan and the Netherlands.²

Summary

Glycogen storage disease type II is a rare disorder that causes insufficient functioning of the enzyme acid alpha-glucosidase, caused by the mutation of the GAA gene. The prevention of producing enough functional acid alpha-glucosidase results in the buildup of glycogen in both the lysosomes and cytoplasm of the cell, leading to cellular damage. The mutations that occur can lead to symptoms like cardiomyopathy, respiratory difficulties, feeding difficulties and many more.² 

This rare condition affects 1 in 40,000 people and the severity of the condition depends on the age of onset when diagnosed. There are two types of pompe disease; infantile-onset and adult-onset pompe disease.² The signs and symptoms that occur for both diseases are different and could potentially result in death. 

Enzyme replacement therapy (ERT) is known to be the most effective method of treatment but is also known for its limitations. However, there are other alternative treatments available.