Background

Pompe disease was the first identified lysosomal storage disorder (inherited metabolic diseases that are characterized by an abnormal build-up of various toxic materials in the body’s cells). It causes damage to muscle by the accumulation of glycogen (which is used as an energy source by the body) within the lysosome due to deficiency of an enzyme called acid alpha-glucosidase (GAA). There is a broad spectrum of Pompe disease types with infantile-onset (starting during childhood) being the most severe. The usual presenting features of the infantile form are worsening weakness of the heart, muscles used in breathing and skeletal muscle. The tongue and the liver may be enlarged. An enlarged liver may be present. This review aims to assess the effectiveness and safety of enzyme replacement therapy in children with infantile-onset Pompe disease.

Search date

The evidence is current to 24 November 2016.

Study characteristics

We searched medical databases for clinical trials of enzyme replacement therapy in children with Pompe disease. We found no randomised trials (where people taking part in the trial have equal chances of being in the treatment or the control group) comparing the effectiveness and safety of enzyme replacement therapy to another intervention, no intervention or placebo (a ‘dummy’ drug). We found one trial (18 children) that compared two doses of recombinant human alglucosidase alfa (an enzyme replacement therapy): 20 mg/kg every two weeks (low dose) and 40 mg/kg every two weeks (high dose). The duration of treatment ranged from 52 weeks (the length of the original study) to up to three years (including the extension phase of the study), with a median (the middle number) duration of treatment being 2.3 years.

Key results

There were very limited numerical results available by dose group, the trial showed no evidence in favour of a high dose as opposed to a low dose. It described that the clinical responses including cardiac function, motor development (development of a child’s muscles and their ability to move around and manipulate their environment), as well as the proportion of children that were free of invasive ventilation,were similar in the two groups (low-quality evidence). Long-term alglucosidase alfa treatment markedly extended survival as well as ventilation-free survival (time without requiring a machine to help with breathing) and improved cardiomyopathy (heart disease) (low-quality evidence). In relation to the number of children experiencing one or more infusion-related events, there was no significant difference between the different dose groups (low-quality evidence), although, of note, at 52 weeks, five children in the low-dose group experienced a total of 41 mild or moderate (none were severe) infusion-related events and the six children in the high dose-group experienced a total of 123 infusion-related events. By the end of the extension phase, five children in the low-dose group experienced a total of 47 infusion-related events and the six children in the high-dose group experienced a total of 177 infusion-related events.

New trials should be undertaken with adequate number of participants to detect effectiveness and safety at different doses of alglucosidase alfa. The main clinical outcomes (i.e. cardiac function, time to ventilation, survival, motor development and side effects) should be standardized when evaluated and reported.

Quality of the evidence

The evidence that this small trial provided to the review was of low quality. The trial was supported by the Genzyme Corporation.