Pompe disease

Also known as: Acid Maltase Deficiency; Alpha 1,4-glucosidase Deficiency; Glycogen Storage disease Type II

Background

Pompe disease is a rare inherited metabolic disorder caused by deficiency of an enzyme that helps in the lysosomal breakdown of glycogen. Glycogen is a complex sugar that is the primary store of glucose for all cells in the body. The accumulation of glycogen in certain organs and tissues, mainly the heart and skeletal muscles, prevents them from functioning normally.

Researchers have described three types of Pompe disease, which differ in severity. These types are known as classic infantile-onset, non-classic infantile-onset and late-onset.

Credits

Medical text written December 2012 by Dr A Broomfield, Specialist Registrar in Metabolic Medicine, Great Ormond Street Hospital, London, UK.

What are the symptoms?

Infantile-onset Pompe disease
This becomes apparent from within a few days to a few months of birth. Infants typically experience myopathy (muscle weakness), hypotonia (poor muscle tone), and a severe thickening of the heart muscle called hypertrophic cardiomyopathy (see entry Cardiomyopathies in Children). The cardiomyopathy results in heart failure (i.e. accumulation of fluids on the lungs) and hepatomegaly (an enlarged liver). The combination of heart failure and with the decreased muscle strength means that children often have with breathing difficulties. Affected infants will also fail to gain weight and grow as expected. They also can suffer from swallowing difficulties. Sadly, if left untreated, this form of Pompe disease can lead to death from heart failure in the first year of life.

Non-classic Infantile-onset Pompe disease
This form of infantile-onset Pompe disease also appears by one year of age. Symptoms are the same as infant-onset except for the absence of the cardiomyopathy.

Late-onset Pompe disease
The late-onset type of Pompe disease may not become apparent until later in childhood, adolescence or more commonly adulthood. Late-onset Pompe disease is usually milder than the infantile-onset forms of this condition and again does not involve the heart. Most individuals with late-onset Pompe disease experience progressive muscle weakness, especially in the legs and the trunk and including the muscles that control breathing. As the condition progresses, breathing problems can become more serious.

What are the causes?

Changes to the GAA gene (known as mutations) cause Pompe disease. The GAA gene provides instructions for producing an enzyme called acid alpha-glucosidase (also known as acid maltase). This enzyme normally breaks down glycogen in a specialised region of the cell that normally recycles worn out cellular components. This part of the cell is called the lysosome.

How is it diagnosed?

In order to diagnose the condition conclusively, an enzyme assay test must be carried out. The test looks at the levels of acid alpha-glucosidase enzyme in the affected child. This can now be done on a simple blood spot test similar to that used in routine newborn screening. All patients will then be referred to a specialised treatment centre for further investigations and assessments.

How is it treated?

An enzyme replacement therapy (ERT), called alglucosidase alfa (Myozyme) has been developed. The ERT is available in England by referral to one of the expert centres for lysosomal storage disease. NHS funding for this very expensive therapy is not assured for every patient and in Scotland it is still proving very difficult for some late-onset patients to access the therapy. It is worth noting that any previous organ damage that occurs prior to treatment is irreversible.

Inheritance patterns and prenatal diagnosis

Inheritance patterns 
The condition is inherited in an autosomal recessive manner.

Prenatal diagnosis 
This is available if the genetic mutation in the family has been identified. Affected families should be referred to a genetic service for further information and support.

Is there support?

Pompe Support Network

Tel: 01730 231554
Email: [email protected]
Website: pompe.uk

The Pompe Support Network are a Charitable Incorporated Organisation (CIO) no. 1186383. The Pompe Support Network aims to benefit the whole Pompe community in many ways including: monitoring and supporting research, sharing information and representing the patient voice across industry, research and the NHS. They also offer several Facebook groups including ones for diet and nutrition, Exercise and Mental Wellbeing.

Group details added December 2019

Information and advice in the UK for Pompe disease is also provided by the Association for Glycogen Storage Diseases (UK) (see entry Glycogen Storage diseases).

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