Pompe disease

Overview

Pompe disease develops when the body lacks, or doesn't properly produce, an enzyme called acid alpha-glucosidase (GAA), whose normal job is breaking down glycogen inside cells. Without enough working GAA, glycogen accumulates in muscle cells and progressively damages them. There are two recognised forms: infantile-onset Pompe disease (IOPD), where GAA activity is very low or absent, and late-onset Pompe disease (LOPD), where some GAA activity remains and symptoms appear anywhere from childhood to adulthood.

Symptoms

IOPD begins within the first few months of life, with low muscle tone, weakness that worsens quickly, feeding difficulties and poor growth, an enlarged heart, breathing problems, an enlarged tongue, delayed motor milestones, and changes to bone development. Left untreated, survival beyond age two is rare — but enzyme replacement therapy has substantially improved outcomes for children with this form.

LOPD is far more variable in both severity and timing. Weakness typically starts in the core — hips, shoulders and torso — and gradually spreads, making stairs, lifting and everyday tasks progressively harder. Breathing muscles can weaken to the point of needing non-invasive ventilation, though heart involvement is uncommon in this form.

Inheritance

Pompe disease is autosomal recessive: a person needs two changed copies of the GAA gene, one inherited from each parent, to be affected. Parents who carry just one changed copy are unaffected carriers.

Getting a diagnosis

A GP refers to a neurologist or metabolic specialist. Diagnosis typically starts with a dried blood spot test measuring GAA enzyme activity, alongside blood tests for GAA and creatine kinase levels, genetic testing to confirm the specific GAA gene change, and a muscle MRI.

Management and outlook

Care involves a multidisciplinary team — metabolic specialists, neurologists, cardiologists, respiratory specialists, physiotherapists and dietitians. The main treatment is enzyme replacement therapy (ERT), which supplies an artificial version of the missing GAA enzyme by intravenous infusion every two weeks; current options include Myozyme and Nexviazyme (both forms) and Pombiliti (for LOPD in adults aged 18 and over).

Regular monitoring of the heart, breathing and swallowing is essential throughout. Aerobic exercise kept below around 70% of maximum capacity is generally recommended, along with a healthy diet and attention to weight management. Before any surgery, careful pre-operative planning matters, and non-invasive ventilation may be needed during and after the procedure.