Lysosomal Storage Disorders

Pompe disease is an inherited glycogen storage disease that affects skeletal and cardiac muscle which has a wide spectrum of severity and that results from a deficiency in a lysosomal enzyme which breaks down glycogen into glucose. It has a severe infantile form that occurs in the first months of life and can be fatal, whereas later onset has a slower progression.

Challenge for rare disease

The most severe cases present in the first year of life, and before ERT was available 90% died before the first birthday. In the pivotal trial, treatment was clearly life saving with most patients surviving beyond one year and into early childhood.

Unfortunately, it became clear with experience that early diagnosis was crucial: patients treated too late might survive, but need 24-hour invasive ventilation for life. Parents and treating clinicians regarded this as very poor outcome of treatment.

Network

The network for lysosomal storage disorders consists of six units which treat adult patients and three which treat children. This network has been meeting twice-yearly for more than 10 years. Patient organisations are full members of the network.

The network has been responsible for developing guidelines for the use of enzyme replacement therapies. These guidelines are discussed and agreed at network meetings. Network meetings are also used to decide when updates are needed. Treatment of Pompe disease with myozyme provides a good example.

Clinical Outcomes

The key outcome of treatment is survival with a good quality of life.

Emerging best practice and innovation from peer learning

The network meetings have been used to develop and update treatment protocols. The first protocol, developed when Myozyme launched commercially, set out guidelines for use. This was updated to set out the situations in which treatment might not be in the patient’s best interest, for example with late diagnosis.

More recently, the collective expertise of the network has been used to debate the place of double-dose therapy in children whose initial response to myozyme is not maintained. Although these changes in treatment protocols may eventually be published in consensus guidelines, network discussion allows for early and full  exploration of the issues.