title: Diagnostic and prognostic value of in vivo proton MR spectroscopy for Zellweger syndrome spectrum patients.
abstract: Defects in the biogenesis of peroxisomes cause a clinically and genetically heterogeneous group of neurometabolic disorders, the Zellweger syndrome spectrum (ZSS). Diagnosis predominantly is based on characteristic clinical symptoms, a typical biochemical profile, as well as on identification of the molecular defect in any of the 12 known human PEX genes. The diagnostic workup can be hindered if the typical clinical symptoms are missing and predicting the clinical course of a given patient is almost unfeasible. As a safe and noninvasive method to analyze specific chemical compounds in localized brain regions, in vivo proton magnetic resonance spectroscopy (MRS) can provide an indication in this diagnostic process and may help predict the clinical course. However, to date, there are very few reports on this topic. In this study, we performed localized in vivo proton MRS without confounding contributions from T1- and T2-relaxation effects at 2 Tesla in a comparably large group of seven ZSS patients. Patients' absolute metabolite concentrations in cortical gray matter, white matter, and basal ganglia were assessed and compared with age-matched control values. Our results confirm and extend knowledge about in vivo MRS findings in ZSS patients. Besides affirmation of nonspecific reduction of N-acetylaspartate + N-acetylaspartylglutamate (tNAA) in combination with lipid accumulation as a diagnostic hint for this disease group, the amount of tNAA loss seems to reflect disease burden and may prove to be of prognostic value regarding the clinical course of an already diagnosed patient.
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Division of Pediatric Neurology, University Medical Center Göttingen, Georg August University Göttingen, Robert-Koch-Strasse 40, 37085, Göttingen, Germany. hendrik.rosewich@med.uni-goettingen.de.
authors.forename: H
authors.identifier: 0000-0003-4692-5511
authors.initials: H
authors.lastname: Rosewich
authors.affiliation: Department of Cognitive Neurology, MR-Research in Neurology and Psychiatry, Georg-August-University of Göttingen, Göttingen, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Dechent
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Division of Pediatric Neurology, University Medical Center Göttingen, Georg August University Göttingen, Robert-Koch-Strasse 40, 37085, Göttingen, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Krause
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Division of Pediatric Neurology, University Medical Center Göttingen, Georg August University Göttingen, Robert-Koch-Strasse 40, 37085, Göttingen, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Ohlenbusch
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Division of Pediatric Neurology, University Medical Center Göttingen, Georg August University Göttingen, Robert-Koch-Strasse 40, 37085, Göttingen, Germany.|Department of Pediatrics and Adolescent Medicine, Interdisciplinary Pediatric Center for Children with Developmental Disabilities and Severe Chronic Disorders, University Medical Center Göttingen, Georg August University Göttingen, Göttingen, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Brockmann
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Division of Pediatric Neurology, University Medical Center Göttingen, Georg August University Göttingen, Robert-Koch-Strasse 40, 37085, Göttingen, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Gärtner
mesh_terms: D000293:Adolescent; D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001479:Basal Ganglia / Q000378:metabolism / Q000473:pathology; D002648:Child; D004151:Dipeptides / Q000378:metabolism; D005260:Female; D066128:Gray Matter / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007223:Infant; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D020675:Peroxisomes / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D011522:Protons; D066127:White Matter / Q000378:metabolism / Q000473:pathology; D055815:Young Adult; D015211:Zellweger Syndrome / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology*
chemical_list: D004151:Dipeptides; D011522:Protons; C027172:isospaglumic acid; D001224:Aspartic Acid; C000179:N-acetylaspartate