title: Cerebral lipid accumulation in Chanarin-Dorfman Syndrome.
abstract: Chanarin-Dorfman Syndrome (CDS) is caused by a defect in the CGI-58/ABHD5 gene resulting in a deficiency of CGI-58 and in intracellular accumulation of triacylglycerol in skin and liver. Patients are mainly characterized by congenital ichthyosis, but the clinical phenotype is very heterogeneous. Distinct brain involvement has never been described. We present a clinical description of two patients with congenital ichthyosis. On suspicion of Sjögren-Larsson syndrome (SLS) single-voxel 1H-MR spectroscopy of the brain was performed and biochemical testing of fatty aldehyde dehydrogenase (FALDH) to establish this diagnosis gave normal results. Vacuolisation in a peripheral blood smear has led to the CDS suspicion. In both patients the diagnosis CDS was confirmed by ABHD5 mutation analysis. Interestingly, a clear lipid accumulation in the cerebral white matter, cortex and basal ganglia was demonstrated in both CDS-patients. These results demonstrate, for the first time, cerebral involvement in CDS and give new insights in the complex phenotype. Since the clinical implications of this abnormal cerebral lipid accumulation are still unknown, further studies are warranted.
authors.affiliation: Department of Laboratory Medicine, Translational Metabolic Laboratory, Radboud University Medical Center, Geert Grooteplein zuid 10, route 830, 6525 GA Nijmegen, The Netherlands.
authors.forename: Marleen C D G
authors.initials: MC
authors.lastname: Huigen
authors.affiliation: Department of Radiology, Radboud University Medical Center, Geert Grooteplein zuid 10, route 766, 6525 GA Nijmegen, The Netherlands; Department of Pediatrics, Radboud University Medical Center, Geert Grooteplein zuid 10, route 804, 6525 GA Nijmegen, The Netherlands.
authors.forename: Marinette
authors.initials: M
authors.lastname: van der Graaf
authors.affiliation: Department of Pediatrics, Radboud University Medical Center, Geert Grooteplein zuid 10, route 804, 6525 GA Nijmegen, The Netherlands; Hayward Genetics Center and Department of Pediatrics, Tulane University Medical School, 1430 Tulane Ave, New Orleans, LA 70112, USA.
authors.forename: Eva
authors.initials: E
authors.lastname: Morava
authors.affiliation: Department of Pediatrics, Deventer Hospital, Nico Bolkensteinlaan 75, 7416 SE, Deventer, The Netherlands.
authors.forename: A Carin M
authors.initials: AC
authors.lastname: Dassel
authors.affiliation: Department of Dermatology and GROW School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands; Department of Clinical Genetics, Maastricht University Medical Centre, Maastricht, The Netherlands; Institute of Medical Biology, Immunos, Singapore.
authors.forename: Maurice A M
authors.initials: MA
authors.lastname: van Steensel
authors.affiliation: Department of Dermatology, Radboud University Medical Center, Geert Grooteplein zuid 10, route 370, 6525 GA Nijmegen, The Netherlands.
authors.forename: Marieke M B
authors.initials: MM
authors.lastname: Seyger
authors.affiliation: Department of Laboratory Medicine, Translational Metabolic Laboratory, Radboud University Medical Center, Geert Grooteplein zuid 10, route 830, 6525 GA Nijmegen, The Netherlands.
authors.forename: Ron A
authors.initials: RA
authors.lastname: Wevers
authors.affiliation: Department of Paediatric Neurology, Radboud University Medical Center, Donders Institute for Brain, Cognition, and Behaviour, Geert Grooteplein zuid 10, route 801, 6525 GA Nijmegen, The Netherlands. Electronic address: Michel.Willemsen@radboudumc.nl.
authors.forename: Michèl A
authors.initials: MA
authors.lastname: Willemsen
mesh_terms: D000328:Adult; D001479:Basal Ganglia / Q000737:chemistry; D001923:Brain Chemistry; D002525:Cerebellar Cortex / Q000737:chemistry; D002648:Child; D005260:Female; D006801:Humans; D016113:Ichthyosiform Erythroderma, Congenital / Q000175:diagnosis / Q000378:metabolism*; D007223:Infant; D008052:Lipid Metabolism, Inborn Errors / Q000175:diagnosis / Q000378:metabolism*; D008055:Lipids / Q000032:analysis*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009135:Muscular Diseases / Q000175:diagnosis / Q000378:metabolism*; D016111:Sjogren-Larsson Syndrome / Q000175:diagnosis; D066127:White Matter / Q000737:chemistry
chemical_list: D008055:Lipids
keywords: Cerebral lipid accumulation; Chanarin–Dorfman Syndrome; Inherited metabolic disease; Neutral lipid storage disease with ichthyosis; Proton MRS