Brain Development in Infantile-Onset Pompe Disease Treated by Enzyme Replacement Therapy

Abstract

ABSTRACT: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 infantileonset 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.

Postmortem Findings and Clinical Correlates in Individuals with Infantile-Onset Pompe Disease

“…Interestingly, the oldest patient in the current case series, patient 1, had dilatation of the ventricles on postmortem examination. Ventricular dilatation was also observed in brain MRI in three of five participants who had serial MRI scanning (Chien et al 2006). Finally, serial MRI in a CRIM-negative patient demonstrated white matter abnormalities despite normal myelination (Rohrbach et al 2010).…”

CRIM‐negative infantile Pompe disease: 42‐month treatment outcome

“…Several early and also more recent studies (Burrow et al 2010;Chen et al 2004;Crome et al 1963;Engel et al 1973;Gambetti et al 1971;Lee et al 1996;Mancall et al 1965;Martin et al 1973) point to abnormalities in the CNS and PNS, leading to a slowly progressive neurodegenerative process. Chien et al reported myelination delay on MRI in five patients started on ERT later than 5.5 months of age (Chien et al 2006). However, initial brain MRI was performed late, all but one patient had significant motor developmental delays, and no information regarding CRIM status, speech and language development, or hearing was provided.…”

Neural deficits contribute to respiratory insufficiency in Pompe disease

“…However, a few Pompe case reports have demonstrated CNS glycogen accumulation (9)(10)(11)(12)(13)(14) and absent or diminished deep tendon reflexes (15,16). In particular, spinal motoneurons seem to be susceptible to excessive glycogen accumulation (10,13,15).…”