Patients with classic infantile-onset Pompe disease (IOPD) often demonstrate widespread white matter brain abnormalities and cognitive impairments compared to patients with late-onset Pompe disease (LOPD), as published in the Journal of Inherited Metabolic Disorders.

Researchers were prompted to examine brain structure and cognitive function in patients with LOPD since the currently approved enzyme replacement therapy (ERT) with recombinant human acid alpha-glucosidase is unable to cross the blood-brain barrier. This would render ERT ineffective in preventing brain abnormalities and cognitive impairment because of the glycogen accumulation caused by the disease.

Investigators conducted this single-center cohort study by enrolling 19 children and adults diagnosed with LOPD aged between 11 and 56 years. Leukocyte and/or fibroblast enzyme analyses and gene mutation analyses confirmed the LOPD diagnoses. Brain magnetic resonance imaging (MRI) included coronal T1, sagittal T2, T2 fluid-attenuated inversion recovery, susceptibility-weighted images, and magnetic resonance angiography-time of flight scanning.

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The angiography scanned for vascular abnormalities within the circle of Willis and the internal carotid arteries. A seasoned neuroradiologist interpreted all study images using the Fazekas scale to quantify white matter abnormalities, and the global cortical atrophy (GCA) scale and medial temporal lobe atrophy (MTA) scale to rate generalized brain and hippocampal atrophy, respectively.

The researchers observed normal MRI and MRA scans in 12 out of the 19 patients. Three patients demonstrated nonspecific focal punctate white matter abnormalities, 2 demonstrated mild punctate white matter abnormalities with Fazekas scores of 1 to 2, and 1 demonstrated mild-to-moderate supratentorial and infratentorial atrophy with GCA scores of 1 to 2 and an MTA score of 1. Two patients demonstrated slight vertebrobasilar dolichoectasias without aneurysms, dissections, or other vascular problems.

The 19 patients also underwent a battery of cognitive tests within 24 hours of the MRI scans. Most patients obtained age-adjusted normal scores for the Intelligence Quotient and neuropsychological tests with a subset of patients (9 of 19) demonstrating the most difficulty with the visuospatial domain copy trial tests.

“Confounding due to motor weakness is unlikely, since none of the included patients exhibited muscle weakness of the hands,” the authors said in response to the unexpected finding of visuospatial drawing difficulties. They suggested future research using larger cohorts with different imaging or neuropsychological testing methods to improve comprehension of this study’s findings.


Van den Dorpel JJA, van der Vlugt WMC, Dremmen MHG, et al. Is the brain involved in patients with late-onset Pompe disease? J Inherit Metab Dis. Published online December 20, 2021. doi:10.1002/jimd.12469