JIMD Reports, Volume 39

Broomfield, A., Fletcher, J., Hensman, P., Wright, R., Prunty, H., Pavaine, J., Jones, S.A., A. Broomfield, J. Fletcher, P. Hensman, R. Wright, H. Prunty, J. Pavaine, S. A. Jones, Jones, S. A.

Glycogen accumulation in the central nervous system of patients with classical infantile onset Pompe disease (IOPD) has been a consistent finding on the few post-mortems performed. While delays in myelination and a possible reduction in processing speed have previously been noted, it has only been recently that the potential for clinically significant progressive white matter disease has been noted. The limited reports thus far published infer that in some IOPD patients, this manifests as intellectual decline in the second decade of life. We present a CRIM negative patient, immunomodulated with rituximab and methotrexate at birth, who despite an initial good clinical response to ERT, at the age of just under 4 years, presented with evolving spasticity in the lower limbs. The investigation of which revealed progressive central nervous system involvement. Given both the earlier onset of the symptoms and consanguineous familial pedigree, extensive biochemical and genetic investigation was undertaken to ensure no alternative pathology was elucidated. In light of these findings, we review the radiology and post-mortems of previous cases and discuss the potential mechanisms that may underlie this presentation.