Proton MRS of a child with Sandhoff disease reveals elevated brain hexosamine
B Wilken1, P Dechent, F Hanefeld
1Abteilung Neuropädiatrie, Department of Pediatric Neurology, Klinikum Kassel, Mönchebergstr. 41-43, 34125 Kassel, Germany. wilken@klinikum-kassel.de
Insights
Sandhoff disease, a severe neurodegenerative disorder, shows specific brain metabolite changes on proton MR spectroscopy. N-acetylhexosamine accumulation is identified as a potential biomarker for this gangliosidosis.
Area of Science:
- Biochemistry
- Neuroscience
- Medical Imaging
Background:
- Sandhoff disease (gangliosidosis type 0) is a fatal lysosomal storage disorder caused by deficient hexosaminidases A and B.
- Affected children experience initially normal development followed by severe, rapid neurodegeneration, including spastic tetraparesis and seizures.
Observation:
- Brain MRI in a 10-month-old girl revealed signal abnormalities in white matter, basal ganglia, and cerebellum.
- Proton MR spectroscopy (MRS) showed reduced N-acetylaspartate and elevated inositol in various brain regions.
- A novel resonance at 2.07 ppm, identified as N-acetylhexosamine, was detected in all examined brain areas.
Findings:
- Conventional MRS findings indicate neuroaxonal damage and astrocytosis, consistent with Sandhoff disease pathology.
- The detected N-acetylhexosamine resonance suggests accumulation of hexosamine-containing oligosaccharides, a specific indicator for Sandhoff disease.
- These findings align with in vitro studies on Sandhoff mouse models.
Implications:
- Proton MRS provides crucial insights into the pathophysiology of Sandhoff disease in children.
- N-acetylhexosamine detected via MRS may serve as a disease-specific biomarker for Sandhoff disease.
- MRS could establish a unique spectral pattern for diagnosing Sandhoff disease in the brain.
Abstract:
Sandhoff disease (gangliosidosis type 0) is a lysosomal storage disorder with a deficiency of hexosaminidases A and B. After an initially normal development the clinical course of affected children is severe and rapidly progressive leading to spastic tetraparesis, epileptic seizures and early death. In a 10-month-old girl with enzymatically established diagnosis of Sandhoff disease MRI of the brain showed signal changes in the periventricular white matter, pyramidal tract, basal ganglia, and cerebellar hemispheres. Proton MR spectroscopy (MRS) at the age of 13 months revealed a reduction of total N-acetylaspartate (neuroaxonal marker) as well as strongly elevated inositol (glial marker) in white matter, gray matter, and basal ganglia. A new resonance at 2.07 ppm was detected in all regions and ascribed to N-acetylhexosamine with highest concentrations in white matter and thalamus. While conventional MRS findings are in line with neuroaxaonal damage and pronounced astrocytosis, the observation of N-acetylhexosamine appears as a specific marker of Sandhoff disease indicating accumulation of hexosamine-containing oligosaccharides. This interpretation is supported by a recent in vitro MRS study of a Sandhoff mouse model. In conclusion, proton MRS of cerebral metabolites offers specific insights into the pathopysiologic processes of children with Sandhoff disease and may prove to represent another disease specific MRS pattern of the brain.
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