Case definition and classification of leukodystrophies and leukoencephalopathies

Adeline Vanderver; Morgan Prust; Davide Tonduti; Fanny Mochel; Heather M Hussey; Guy Helman; James Garbern; Florian Eichler; Pierre Labauge; Patrick Aubourg; Diana Rodriguez; Marc C Patterson; Johan L K Van Hove; Johanna Schmidt; Nicole I Wolf; Odile Boespflug-Tanguy; Raphael Schiffmann; Marjo S van der Knaap; GLIA Consortium

doi:10.1016/j.ymgme.2015.01.006

Case definition and classification of leukodystrophies and leukoencephalopathies

Mol Genet Metab. 2015 Apr;114(4):494-500. doi: 10.1016/j.ymgme.2015.01.006. Epub 2015 Jan 29.

Authors

Adeline Vanderver¹, Morgan Prust², Davide Tonduti³, Fanny Mochel⁴, Heather M Hussey⁵, Guy Helman², James Garbern⁶, Florian Eichler⁷, Pierre Labauge⁸, Patrick Aubourg⁹, Diana Rodriguez¹⁰, Marc C Patterson¹¹, Johan L K Van Hove¹², Johanna Schmidt², Nicole I Wolf¹³, Odile Boespflug-Tanguy¹⁴, Raphael Schiffmann¹⁵, Marjo S van der Knaap¹³; GLIA Consortium

Affiliations

¹ Department of Neurology and Center for Genetic Medicine Research, Children's National Health System, Washington DC, USA; Department of Integrated Systems Biology, George Washington University School of Medicine, Washington DC, USA. Electronic address: avanderv@childrensnational.org.
² Department of Neurology and Center for Genetic Medicine Research, Children's National Health System, Washington DC, USA.
³ Child Neuropsychiatry Unit, Department of Brain and Behavioral Sciences, University of Pavia, Italy; Department of Child Neurology, Fondazione IRCCS Istituto Neurologico "Carlo Besta", Milan, Italy.
⁴ INSERM U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM and APHP, Department of Genetics, Groupement Hospitalier Pitié-Salpêtrière-Charles Foix, Paris, France.
⁵ Milken Institute School of Public Health, The George Washington University, Washington DC, USA.
⁶ University of Rochester, Rochester, NY, USA.
⁷ Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁸ Department of Neurology, CHU Montpellier, Montpellier, France.
⁹ Department of Pediatric Neurology-Inserm U986, Hôpital Bicêtre, 78 avenue du Général Leclerc, 94275 Le Kremlin-Bicêtre, France.
¹⁰ APHP, Service de Neuropédiatrie, Hôpital Armand Trousseau, UPMC Universite, Paris 06, Inserm U676, Paris, France.
¹¹ Departments of Neurology, Pediatrics and Medical Genetics, Mayo Clinic, Rochester, MN, USA.
¹² Section of Genetics, Department of Pediatrics, University of Colorado, Aurora, CO, USA.
¹³ Department of Child Neurology, VU University Medical Center and Neuroscience Campus, Amsterdam, The Netherlands.
¹⁴ Department of Pediatric Neurology and Metabolic Disorders, French Reference Center for Leukodystrophies, Robert Debré Hospital, Paris, France; Inserm UMR1141 Neuroprotect, Paris Diderot University, Sorbonne Cite, Paris, France.
¹⁵ Institute of Metabolic Disease, Baylor Research Institute, Dallas, TX, USA.

Abstract

Objective: An approved definition of the term leukodystrophy does not currently exist. The lack of a precise case definition hampers efforts to study the epidemiology and the relevance of genetic white matter disorders to public health.

Method: Thirteen experts at multiple institutions participated in iterative consensus building surveys to achieve definition and classification of disorders as leukodystrophies using a modified Delphi approach.

Results: A case definition for the leukodystrophies was achieved, and a total of 30 disorders were classified under this definition. In addition, a separate set of disorders with heritable white matter abnormalities but not meeting criteria for leukodystrophy, due to presumed primary neuronal involvement and prominent systemic manifestations, was classified as genetic leukoencephalopathies (gLE).

Interpretation: A case definition of leukodystrophies and classification of heritable white matter disorders will permit more detailed epidemiologic studies of these disorders.

Keywords: Genetic leukoencephalopathy; Glia; Leukodystrophy; Myelin.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

MeSH terms

Brain Diseases / classification
Demyelinating Diseases* / classification
Humans
Leukoencephalopathies* / classification
Leukoencephalopathies* / genetics
Lysosomal Storage Diseases* / classification
Myelin Sheath / physiology
Neuroglia / physiology

Abstract

Publication types

MeSH terms

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