Abstract
Leukodystrophies (adrenoleukodystrophy, metachromatic leukodystrophy, Krabbe disease, polyglucosan body disease, etc.) are a highly heterogeneous group of hereditary diseases primarily affecting the white matter of the central nervous system.
Adult-onset (≥16 years) leukodystrophies are characterized by relentless progression. For the diseases that usually have infantile or childhood onset, the prognosis is very severe, while it is typically better for the adult-onset forms.
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References
van der Knaap MS, Volk J. Magnetic resonance of myelination and myelin disorders. Berlin/New York: Springer; 2005.
Ahmed RM, Murphy E, Davagnanam I, et al. A practical approach to diagnosing adult onset leukodystrophies. J Neurol Neurosurg Psychiatry. 2014;85:770–81.
Costello DJ, Eichler AF, Eichler FS. Leukodystrophies: classification, diagnosis and treatment. Neurologist. 2009;15:319–28.
Dobyns WB, Filauro A, Tomson BN, et al. Inheritance of most X-linked traits is not dominant or recessive, just X-linked. Am J Med Genet A. 2004;129A:136–43.
Engelen M, Barbier M, Dijkstra IM, et al. X-linked adrenoleukodystrophy in women: a cross-sectional cohort study. Brain. 2014;137:693–706.
Salsano E, Tabano S, Sirchia SM, et al. Preferential expression of mutant ABCD1 allele is common in adrenoleukodystrophy female carriers but unrelated to clinical symptoms. Orphanet J Rare Dis. 2012;7:10.
Semmler A, Köhler W, Jung HH, Weller M, Linnebank M. Therapy of X-linked adrenoleukodystrophy. Expert Rev Neurother. 2008;8:1367–79.
Cartier N, Aubourg P. Hematopoietic stem cell transplantation and hematopoietic stem cell gene therapy in X-linked adrenoleukodystrophy. Brain Pathol. 2010;20:857–62.
van Geel BM, Poll-The BT, Verrips A, et al. Hematopoietic cell transplantation does not prevent myelopathy in X-linked adrenoleukodystrophy: a retrospective study. J Inherit Metab Dis. 2015;38:359–61.
van Geel BM, Bezman L, Loes DJ, Moser HW, Raymond GV. Evolution of phenotypes in adult male patients with X-linked adrenoleukodystrophy. Ann Neurol. 2001;49:186–94.
de Beer M, Engelen M, van Geel BM. Frequent occurrence of cerebral demyelination in adrenomyeloneuropathy. Neurology. 2014;83:2227–31.
Rauschka H, Colsch B, Baumann N, et al. Late-onset metachromatic leukodystrophy: genotype strongly influences phenotype. Neurology. 2006;67:859–63.
Solders M, Martin DA, Andersson C, et al. Hematopoietic SCT: a useful treatment for late metachromatic leukodystrophy. Bone Marrow Transplant. 2014;49:1046–51.
Biffi A, Montini E, Lorioli L, Cesani M, et al. Lentiviral hematopoietic stem cell gene therapy benefits metachromatic leukodystrophy. Science. 2013;341(6148):1233158.
Debs R, Froissart R, Aubourg P, et al. Krabbe disease in adults: phenotypic and genotypic update from a series of 11 cases and a review. J Inherit Metab Dis. 2013;36:859–68.
Krivit W, Shapiro EG, Peters C, et al. Hematopoietic stem-cell transplantation in globoid-cell leukodystrophy. N Engl J Med. 1998;338:1119–26.
Mochel F, Schiffmann R, Steenweg ME, et al. Adult polyglucosan body disease: Natural History and Key Magnetic Resonance Imaging Findings. Ann Neurol. 2012;72:433–41.
Padiath QS, Fu YH. Autosomal dominant leukodystrophy caused by lamin B1 duplications a clinical and molecular case study of altered nuclear function and disease. Methods Cell Biol. 2010;98:337–57.
Potic A, Pavlovic AM, Uziel G, et al. Adult-onset autosomal dominant leukodystrophy without early autonomic dysfunctions linked to lamin B1 duplication: a phenotypic variant. J Neurol. 2013;260:2124–9.
Baba Y, Ghetti B, Baker MC, et al. Hereditary diffuse leukoencephalopathy with spheroids: clinical, pathologic and genetic studies of a new kindred. Acta Neuropathol. 2006;111:300–11.
Sundal C, Wszolek Z. CSF1R-related hereditary diffuse leukoencephalopathy with spheroids. 2012. [updated 2013 Jan 17]. In: Pagon RA, Adam MP, Ardinger HH, Bird TD, Dolan CR, et al., editors. GeneReviews® [Internet]. Seattle: University of Washington, Seattle; 1993–2014. Available from http://www.ncbi.nlm.nih.gov/books/NBK100239/PubMed.
Guerreiro RJ, Lohmann E, Brás JM, et al. Using exome sequencing to reveal mutations in TREM2 presenting as a frontotemporal dementia-like syndrome without bone involvement. JAMA Neurol. 2013;70:78–84.
Kaneko M, Sano K, Nakayama J, Amano N. Nasu-Hakola disease: The first case reported by Nasu and review: The 50th Anniversary of Japanese Society of Neuropathology. Neuropathology. 2010;30:463–70.
Haruta K, Matsunaga S, Ito H, et al. Membranous lipodystrophy (Nasu-Hakola disease) presenting an unusually benign clinical course. Oncol Rep. 2003;10:1007–10.
van der Knaap MS, Pronk JC, Scheper GC. Vanishing white matter disease. Lancet Neurol. 2006;5:413–23.
Labauge P, Horzinski L, Ayrignac X, et al. Natural history of adult-onset eIF2B-related disorders: a multi-centric survey of 16 cases. Brain. 2009;132:2161–9.
Schiffmann R, Fogli A, Van der Knaap MS, Boespflug-Tanguy O. Childhood ataxia with central nervous system hypomyelination/vanishing white matter. 2003. [updated 2012 Aug 09]. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong CT, Stephens K, editors. GeneReviews™ [Internet]. Seattle: University of Washington, Seattle; 1993–2013. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1258/PubMed.
Prust M, Wang J, Morizono H, Messing A, et al. GFAP mutations, age at onset, and clinical subtypes in Alexander disease. Neurology. 2011;77:1287–94.
Pareyson D, Fancellu R, Mariotti C, et al. Adult-onset alexander disease: a series of eleven unrelated cases with review of the literature. Brain. 2008;131:2321–31.
van Berge L, Hamilton EM, Linnankivi T, et al. Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation: clinical and genetic characterization and target for therapy. Brain. 2014;137:1019–29.
Hobson GM, Garbern JY. Pelizaeus-Merzbacher disease, Pelizaeus-Merzbacher-like disease 1, and related hypomyelinating disorders. Semin Neurol. 2012;32:62–7.
Grossi S, Regis S, Biancheri R, Mort M, et al. Molecular genetic analysis of the PLP1 gene in 38 families with PLP1-related disorders: identification and functional characterization of 11 novel PLP1 mutations. Orphanet J Rare Dis. 2011;6:40.
Orthmann-Murphy JL, Salsano E, Abrams CK, Bizzi A, Uziel G, Freidin MM, Lamantea E, Zeviani M, Scherer SS, Pareyson D. Hereditary spastic paraplegia is a novel phenotype for GJA12/GJC2 mutations. Brain. 2009;132:426–38.
Abrams CK, Scherer SS, Flores-Obando R, Freidin MM, Wong S, Lamantea E, Farina L, Scaioli V, Pareyson D, Salsano E. A new mutation in GJC2 associated with subclinical leukodystrophy. J Neurol. 2014;261:1929–38.
Depienne C, Bugiani M, Dupuits C, et al. Brain white matter oedema due to ClC-2 chloride channel deficiency: an observational analytical study. Lancet Neurol. 2013;12:659–68.
Di Bella D, Pareyson D, Savoiardo M, Farina L, Ciano C, Caldarazzo S, Sagnelli A, Bonato S, Nava S, Bresolin N, Tedeschi G, Taroni F, Salsano E. Subclinical leukodystrophy and infertility in a man with a novel homozygous CLCN2 mutation. Neurology. 2014;83:1217–8.
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Salsano, E., Pareyson, D. (2015). Leukodystrophies. In: Sghirlanzoni, A., Lauria, G., Chiapparini, L. (eds) Prognosis of Neurological Diseases. Springer, Milano. https://doi.org/10.1007/978-88-470-5755-5_14
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DOI: https://doi.org/10.1007/978-88-470-5755-5_14
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