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Detecting Glycogen in Peripheral Blood Mononuclear Cells with Periodic Acid Schiff Staining
Published on: December 23, 2014
Brain glycogen build-up measured by magnetic resonance spectroscopy in classic infantile Pompe disease
Chloé Najac1, Nadine A M E van der Beek2, Vincent O Boer3
1C.J. Gorter MRI Center, Department of Radiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
Insights
Classic infantile Pompe disease causes brain glycogen buildup and cognitive decline. Magnetic resonance spectroscopy non-invasively detected this glycogen accumulation and neuronal damage in patients, offering a new diagnostic tool.
Area of Science:
- Neuroscience
- Biochemistry
- Medical Imaging
Background:
- Classic infantile Pompe disease involves lysosomal glycogen accumulation due to acid α-glucosidase deficiency.
- Current treatments improve survival but do not cross the blood-brain barrier, leading to progressive neurological deficits in patients.
- Cognitive deficits and white matter lesions are common in surviving patients, highlighting the need for brain-specific monitoring.
Purpose of the Study:
- To assess the feasibility of non-invasively measuring brain glycogen buildup and metabolic changes in classic infantile Pompe disease.
- To investigate the utility of advanced MRI techniques for detecting neuropathology in affected children.
- To establish a potential imaging biomarker for disease progression and cognitive decline.
Main Methods:
- Utilized a 7 Tesla MRI scanner for high-resolution imaging.
- Employed T2-weighted MRI to identify white matter lesions.
- Applied 1H magnetic resonance spectroscopy (MRS) and MRS imaging (MRSI) to determine neurochemical profiles and their spatial distribution.
Main Results:
- All Pompe disease patients exhibited widespread white matter lesions on T2-weighted MRI.
- MRS and MRSI revealed significantly increased brain glycogen and decreased N-acetyl-aspartate (neuronal marker) in patients compared to controls.
- These findings indicate a clear shift in the brain's neurochemical profile consistent with the disease pathology.
Conclusions:
- 1H magnetic resonance spectroscopy (imaging) shows significant potential as a non-invasive tool to visualize Pompe disease brain pathology.
- This technique could enable monitoring of disease progression and correlation with cognitive decline in affected individuals.
- Further research is warranted to validate MRS/MRSI for clinical use in Pompe disease management.
Abstract:
Classic infantile Pompe disease is caused by abnormal lysosomal glycogen accumulation in multiple tissues, including the brain due to a deficit in acid α-glucosidase. Although treatment with recombinant human acid α-glucosidase has dramatically improved survival, recombinant human acid α-glucosidase does not reach the brain, and surviving classic infantile Pompe patients develop progressive cognitive deficits and white matter lesions. We investigated the feasibility of measuring non-invasively glycogen build-up and other metabolic alterations in the brain of classic infantile Pompe patients. Four classic infantile patients (8-16 years old) and 4 age-matched healthy controls were scanned on a 7 T MRI scanner. We used T2-weighted MRI to assess the presence of white matter lesions as well as 1H magnetic resonance spectroscopy and magnetic resonance spectroscopy imaging to obtain the neurochemical profile and its spatial distribution, respectively. All patients had widespread white matter lesions on T2-weighted images. Magnetic resonance spectroscopy data from a single volume of interest positioned in the periventricular white matter showed a clear shift in the neurochemical profile, particularly a significant increase in glycogen (result of acid α-glucosidase deficiency) and decrease in N-acetyl-aspartate (marker of neuronal damage) in patients. Magnetic resonance spectroscopy imaging results were in line and showed a widespread accumulation of glycogen and a significant lower level of N-acetyl-aspartate in patients. Our results illustrate the unique potential of 1H magnetic resonance spectroscopy (imaging) to provide a non-invasive readout of the disease pathology in the brain. Further study will assess its potential to monitor disease progression and the correlation with cognitive decline.
