A clinical approach to the diagnosis of patients with leukodystrophies and genetic leukoencephelopathies

Parikh, Sumit, Bernard, Geneviève, Leventer, Richard J., van der Knaap, Marjo S., van Hove, Johan, Pizzino, Amy, McNeill, Nathan H., Helman, Guy, Simons, Cas, Schmidt, Johanna L., Rizzo, William B., Patterson, Marc C., Taft, Ryan J., Vanderver, Adeline and on behalf of the GLIA Consortium (2015) A clinical approach to the diagnosis of patients with leukodystrophies and genetic leukoencephelopathies. Molecular Genetics and Metabolism, 114 4: 501-515. doi:10.1016/j.ymgme.2014.12.434

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Author Parikh, Sumit
Bernard, Geneviève
Leventer, Richard J.
van der Knaap, Marjo S.
van Hove, Johan
Pizzino, Amy
McNeill, Nathan H.
Helman, Guy
Simons, Cas
Schmidt, Johanna L.
Rizzo, William B.
Patterson, Marc C.
Taft, Ryan J.
Vanderver, Adeline
on behalf of the GLIA Consortium
Total Author Count Override 14
Title A clinical approach to the diagnosis of patients with leukodystrophies and genetic leukoencephelopathies
Journal name Molecular Genetics and Metabolism   Check publisher's open access policy
ISSN 1096-7206
Publication date 2015-04-01
Year available 2014
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1016/j.ymgme.2014.12.434
Open Access Status
Volume 114
Issue 4
Start page 501
End page 515
Total pages 15
Place of publication Waltham, MA United States
Publisher Academic Press
Collection year 2015
Language eng
Abstract Leukodystrophies (LD) and genetic leukoencephalopathies (gLE) are disorders that result in white matter abnormalities in the central nervous system (CNS). Magnetic resonance (MR) imaging (MRI) has dramatically improved and systematized the diagnosis of LDs and gLEs, and in combination with specific clinical features, such as Addison’s disease in Adrenoleukodystrophy or hypodontia in Pol-III related or 4H leukodystrophy, can often resolve a case with a minimum of testing. The diagnostic odyssey for the majority LD and gLE patients, however, remains extensive – many patients will wait nearly a decade for a definitive diagnosis and at least half will remain unresolved. The combination of MRI, careful clinical evaluation and next generation genetic sequencing holds promise for both expediting the diagnostic process and dramatically reducing the number of unresolved cases. Here we present a workflow detailing the Global Leukodystrophy Initiative (GLIA) consensus recommendations for an approach to clinical diagnosis, including salient clinical features suggesting a specific diagnosis, neuroimaging features and molecular genetic testing. We also discuss recommendations on the use of broad-spectrum next-generation sequencing in instances of ambiguous MRI or clinical findings. We conclude with a proposal for systematic trials of genome-wide agnostic testing as a first line diagnostic in LDs and gLEs given the increasing number of genes associated with these disorders.
Keyword Glia
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: Official 2015 Collection
Institute for Molecular Bioscience - Publications
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