Title |
A clinical approach to the diagnosis of patients with leukodystrophies and genetic leukoencephelopathies
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Published in |
Molecular Genetics & Metabolism, December 2014
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DOI | 10.1016/j.ymgme.2014.12.434 |
Pubmed ID | |
Authors |
Sumit Parikh, Geneviève Bernard, Richard J. Leventer, Marjo S. van der Knaap, Johan van Hove, Amy Pizzino, Nathan H. McNeill, Guy Helman, Cas Simons, Johanna L. Schmidt, William B. Rizzo, Marc C. Patterson, Ryan J. Taft, Adeline Vanderver, on behalf of the GLIA Consortium |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 2 | 29% |
Italy | 1 | 14% |
United Kingdom | 1 | 14% |
India | 1 | 14% |
Unknown | 2 | 29% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 7 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Colombia | 1 | <1% |
Italy | 1 | <1% |
South Africa | 1 | <1% |
Spain | 1 | <1% |
United States | 1 | <1% |
Unknown | 229 | 98% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 30 | 13% |
Student > Ph. D. Student | 25 | 11% |
Student > Bachelor | 24 | 10% |
Other | 23 | 10% |
Student > Postgraduate | 22 | 9% |
Other | 67 | 29% |
Unknown | 43 | 18% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 98 | 42% |
Neuroscience | 37 | 16% |
Biochemistry, Genetics and Molecular Biology | 17 | 7% |
Agricultural and Biological Sciences | 10 | 4% |
Nursing and Health Professions | 4 | 2% |
Other | 12 | 5% |
Unknown | 56 | 24% |