Brain development in infantile-onset Pompe disease treated by enzyme replacement therapy.

The primary manifestations of Pompe disease are muscle weakness and cardiomyopathy. Although accumulation of glycogen has also been seen in the nervous system in patients, the significance of brain involvement in infantile-onset Pompe disease is not clear. In this study, brain development in five cases of infantile-onset Pompe disease, whose survivals have been prolonged by enzyme replacement therapy (ERT), were studied by brain magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). The results revealed delay in myelination milestones in all patients at a median age of 6 mo upon the initiation of treatment. After ERT, four of the five cases showed good progression in myelination, even though mild dilatation of the ventricles was still observed. In the case with no response to ERT in the muscles, however, brain myelination was slow and follow-up MRI and MRS studies suggested both neuron and myelination loss. Therefore, myelination defects are common in infantile-onset Pompe disease. Improvement in brain myelination could be seen in those who survive by effective treatment, although we do not know whether ERT does have a direct therapeutic effect on the brain.