Cerebral MRI as a valuable diagnostic tool in Zellweger spectrum patients
Abstract
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.
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In some PBD cases, mild initial symptoms are later followed by severe CNS demyelination and death.
“In some cases, mild initial symptoms are later followed by severe CNS demyelination and death of the patient [53,55,56].”
From Peroxisomes in brain development and function (2016) · cites this paper as [53]
Within their first year of life, all patients with Zellweger syndrome display white matter abnormalities in the CNS, observed by histological analyses and brain magnetic resonance tomography.
“In addition to these migration defects, within their first year of life, all patients with Zellweger syndrome display white matter abnormalities in the CNS, which have been observed by histological analyses and brain magnetic resonance tomography (MRT) studies [52–55].”
From Peroxisomes in brain development and function (2016) · cites this paper as [53]
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Peroxisomes in brain development and function
Berger, J., Dorninger, F., Forss-Petter, S., & Kunze, M. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2015.12.005 · Cited by 194 · see citing works
“In some cases, mild initial symptoms are later followed by severe CNS demyelination and death of the patient [53,55,56].”
BackgroundClinical diagnosis, biochemical findings and MRI spectrum of peroxisomal disorders
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- Authors
- Weller, S., Rosewich, H., & Gärtner, J.
- Affiliations
- Department of Pediatrics and Pediatric Neurology Georg August University Robert‐Koch‐Strasse 40 Göttingen 37075 Germany
- University of Göttingen (DE)
- Venue
- Journal of Inherited Metabolic Disease
- Publisher
- Wiley
- Published
- 2008-04
- Volume
- 31
- Issue
- 2
- Pages
- 270-280
- ISSN
- 0141-8955 (ISSN-L)
- 1573-2665
- OpenAlex
- W2050837335
- Cited by
- 58
- References
- 48
- Citations by year
- 2026: 2 · 2024: 2 · 2023: 3 · 2022: 1 · 2021: 6 · 2019: 3 · 2018: 4 · 2017: 3 · 2016: 7 · 2015: 6 · 2014: 3 · 2013: 3 · 2012: 7
- FWCI
- 1.76
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Inherited Metabolic Disease (publishedVersion)
- PubMed (publishedVersion)
- GRO (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (GA354/5–1, 5–2)
- Fritz Thyssen Stiftung (Az.10.05.2.197)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Fetal and Pediatric Neurological Disorders
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Keywords
- peroxisome biogenesis disorders, brain MRI, polymicrogyria, pachygyria, leukoencephalopathy, heterotopia, brain atrophy, delayed myelination, differential diagnosis, mouse model, peroxisomal disorders
- MeSH terms
- Animals, Brain, Child, Preschool, Diagnosis, Differential, Disease Models, Animal, DNA Mutational Analysis, Humans, Infant, Infant, Newborn, Magnetic Resonance Imaging, Mutation, Phenotype, Predictive Value of Tests, Prognosis, Severity of Illness Index, Zellweger Syndrome, Genetic Predisposition to Disease, Mice
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