Cerebral MRI as a valuable diagnostic tool in Zellweger spectrum patients
Patients with defects in the biogenesis of peroxisomes include those with Zellweger syndrome spectrum (ZSS), a developmental and progressive metabolic disease with a distinct dysmorphic phenotype and varying severity. The diagnosis of ZSS relies on the clinical presentation and the biochemical evaluation of peroxisomal metabolites. Mutation detection in one out of twelve genes coding for proteins involved in the biogenesis of peroxisomes confirms the diagnosis. In the absence of pronounced clinical features of ZSS, neuroradiological findings may lead the way to the diagnosis. Cerebral magnetic resonance imaging (cMRI) pathology in ZSS consists of abnormal gyration pattern including polymicrogyria and pachygyria, leukencephalopathy, germinolytic cysts and heterotopias as reported by previous systematic studies including cMRI of a total of 34 ZSS patients, only five of whom had a severe phenotype. The present study evaluated the cMRI results of additional 18 patients, 6 with a severe and 12 with a milder ZSS phenotype. It confirms and extends knowledge of the characteristic cMRI pattern in ZSS patients. Besides an abnormal gyration pattern and delayed myelination or leukencephalopathy, brain atrophy was a common finding. Polymicrogyria and pachygyria were more common in patients with severe ZSS, while leukencephalopathy increases with age in patients with longer survival. Nevertheless, an abnormal gyration pattern might be more frequent in patients with a mild ZSS than deduced from previous studies. In addition, we discuss the differential diagnosis of the ZSS cMRI pattern and review investigations on the pathogenesis of the ZSS cerebral phenotype in mouse models of the disease.
KeywordsBrain Atrophy Zellweger Syndrome Refsum Disease Rhizomelic Chondrodysplasia Punctata Infantile Refsum Disease
cerebral magnetic resonance imaging
infantile Refsum disease
magnetic resonance spectroscopy
peroxisome biogenesis disorder
rhizomelic chondrodysplasia punctata
very long-chain fatty acid
Zellweger syndrome spectrum
We thank Professor Volkher Engelbrecht, Department of Radiology, Klinikum St. Marien Amberg, Germany, for help in evaluating part of the cMRIs. This work was supported by the Deutsche Forschungsgemeinschaft, grants nos. GA354/5–1 and 5–2 (J.G.), the Fritz Thyssen-Stiftung grant no. Az.10.05.2.197 (S.W.) and the Faculty of Medicine research grant from the Georg August University Göttingen (S.W., H.R.).
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