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A new metabolite contributing to N-acetyl signal in 1H MRS of the brain in Salla disease

From the Departments of Medical Genetics (Drs. Varho and Aula), Pediatric Neurology (Drs. Varho, Holopainen, and Sillanpää), Diagnostic Radiology (Drs. Komu, Sonninen, and Lundbom, and S. Nyman), and Anesthesiology (Dr. Manner), University of Turku, Finland.

Address correspondence and reprint requests to Dr. Tarja Varho, Department of Medical Genetics, University of Turku, Kiinamyllynkatu 10, FIN-20520 Turku, Finland.

OBJECTIVE: To determine whether N-acetylaspartate (NAA) is reduced in patients with Salla disease, a neurodegenerative disorder.

BACKGROUND: ^{1H MRS allows the brain metabolism to be studied noninvasively in vivo. N-acetyl (NA) is composed primarily of NAA, which is regarded as a neuronal marker. The NA signal in 1}H MRS is reduced in several neurodegenerative disorders. Increased NA signal has thus far only been found in Canavan’s disease as a result of NAA accumulation in the brain tissue. In Salla disease, an autosomal recessive free sialic acid storage disorder, N-acetylneuraminic acid (NANA), accumulates in lysosomes of brain tissue.

METHODS: The authors studied eight patients with Salla disease (age range, 6 to 44 years) and eight age-matched healthy volunteers using quantitative ¹H MRS. The spectra were obtained from two selected 8-cm³ volumes of interest localized in the basal ganglia and in the parietal white matter using conventional 1.5-T MRI equipment. The spectral resonance lines of NA groups, creatine and phosphocreatine (Cr), and choline-containing compounds (Cho) were analyzed quantitatively. All MR images were evaluated to verify the state of myelination.

RESULTS: ¹H MRS from parietal white matter revealed 34% higher NA and 47% higher Cr concentrations, and a 35% lower Cho concentration in the patients with Salla disease compared with the age-matched control subjects. The patients had a 22% higher water content in their parietal white matter, whereas in the basal ganglia the water concentrations did not differ significantly. In the patients’ basal ganglia the Cr concentration was 53% higher.

CONCLUSIONS: NAA is considered to be a neuronal marker that, except for Canavan’s disease, has been found or assumed to be either stable or reduced. However, in Salla disease the high NA signal may have a contribution from accumulated lysosomal NANA, which offsets the possible loss of NAA. The high Cr is in line with the increased glucose uptake found in our earlier 2-fluoro-2-deoxy-D-glucose-PET study, reflecting increased energy demand. It is worth noting that in a conventional ¹H MRS ratio-based analysis these underlying abnormalities would have remained undetected. Our study thus emphasizes the importance of a quantitative assessment of metabolite concentrations in ¹H MRS for detecting altered brain metabolism.

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