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From the Department of Pediatrics (Drs. Barth, Vreken, and Wanders, and J. Gootjes), and the Laboratory of Genetic Metabolic Disease (Drs. Vreken and Wanders, and J. Gootjes), Emma Children’s Hospital/AMC, and the Department of Radiology (Dr. Majoie), Academic Medical Center (AMC), University of Amsterdam, The Netherlands; and Sozialpädiatrisches Zentrum und Kinderneurologie (Dr. Bode), Universitätskinderklinik und Poliklinik, Ulm, Germany.
Address correspondence and reprint requests to Prof. Dr. Peter G. Barth, Department of Pediatric Neurology, Emma Children’s Hospital/AMC, Room H8-241, P.O. Box 22700, 1100 DE Amsterdam, the Netherlands; e-mail: p.g.barth{at}amc.uva.nl
Objective:— To report late onset cerebral white matter disease as a distinctive phenotype in peroxisome biogenesis disorder (PBD).
Background:— There is phenotypic and genetic overlap among the PBD known as Zellweger syndrome (ZS), infantile Refsum disease (IRD), and neonatal adrenoleukodystrophy (NALD). Distinctive external features are variable among these three disorders, and neurologic deficit has its onset at birth or in infancy. In a structured follow-up cohort of 25 patients with PBD, not including ZS, three patients had an unusual pattern of cerebral white matter disease with onset past the age of 1, not conforming to any of the classic PBD phenotypes.
Methods:— Clinical phenotyping and follow-up, peroxisomal biochemical determinations in body fluids and fibroblasts, identification of affected PEX gene by genetic complementation in fibroblasts, and MRI studies.
Results:— Two unrelated patients with PBD without distinctive external features had normal neurodevelopmental milestones during their first year, followed by rapid deterioration including severe hypotonic pareses, seizures, retinopathy, and deafness. A third patient initially diagnosed with IRD developed cerebral white matter degeneration in the third year of life, complicating the original diagnosis. MRI in all three patients showed cerebral demyelination with sparing of subcortical fibers and pronounced central cerebellar demyelination.
Conclusions:— Late-onset cerebral white matter disease may occur in PBD, either following IRD or following normal early development and in the absence of distinctive external features. Peroxisome biogenesis disorder should be included in the differential diagnosis of post-infantile onset of cerebral white matter disease.
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  B. S. M. ter Rahe, C. B. L. M. Majoie, E. M. Akkerman, G. J. den Heeten, B. T. Poll-The, and P. G. Barth Peroxisomal Biogenesis Disorder: Comparison of Conventional MR Imaging with Diffusion-Weighted and Diffusion-Tensor Imaging Findings AJNR Am. J. Neuroradiol., June 1, 2004; 25(6): 1022 - 1027. [Abstract] [Full Text] [PDF]
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 P. G. Barth, C. B.L.M. Majoie, J. Gootjes, R. J.A. Wanders, H. R. Waterham, M. S. van der Knaap, J. B.C. de Klerk, J. Smeitink, and B. T. Poll-The Neuroimaging of peroxisome biogenesis disorders (Zellweger spectrum) with prolonged survival Neurology, February 10, 2004; 62(3): 439 - 444. [Abstract] [Full Text] [PDF]
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J. Gootjes, P.A.W. Mooijer, C. Dekker, P.G. Barth, B.T. Poll-The, H.R. Waterham, and R.J.A. Wanders Biochemical markers predicting survival in peroxisome biogenesis disorders Neurology, December 10, 2002; 59(11): 1746 - 1749. [Abstract] [Full Text] [PDF]
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