Leukodystrophies are a heterogeneous group of inherited disorders with highly variable clinical manifestations and pathogenetic background
Leukodystrophies are characterized by primary glial cell and myelin sheath pathology of variable aetiology; secondary axonal pathology can emerge as the disease progresses
Around 20 distinct disorders are currently defined as adulthood leukodystrophies; additional involvement of grey matter structures or non-cerebral organs distinguishes these conditions from other genetic leukoencephalopathies
Increasing numbers of individual leukodystrophies are being treated using metabolic treatment strategies, enzyme replacement or cell-based options such as allogeneic haematopoietic stem cell transplantation and gene therapy
The leukodystrophies are a group of inherited white matter disorders with a heterogeneous genetic background, considerable phenotypic variability and disease onset at all ages. This Review focuses on leukodystrophies with major prevalence or primary onset in adulthood. We summarize 20 leukodystrophies with adult presentations, providing information on the underlying genetic mutations and on biochemical assays that aid diagnosis, where available. Definitions, clinical characteristics, age of onset, MRI findings and treatment options are all described, providing a comprehensive overview of the current knowledge of the various adulthood leukodystrophies. We highlight the distinction between adult-onset leukodystrophies and other inherited disorders with white matter involvement, and we propose a diagnostic pathway for timely recognition of adulthood leukodystrophies in a routine clinical setting. In addition, we provide detailed clinical information on selected adult-onset leukodystrophies, including X-linked adrenoleukodystrophy, metachromatic leukodystrophy, cerebrotendinous xanthomatosis, hereditary diffuse leukoencephalopathy with axonal spheroids, autosomal dominant adult-onset demyelinating leukodystrophy, adult polyglucosan body disease, and leukoencephalopathy with vanishing white matter. Ultimately, this Review aims to provide helpful suggestions to identify treatable adulthood leukodystrophies at an early stage in the disease course.
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The authors thank the patients and their families for their long-lasting confidence and abundance of patience while waiting for relief from the disease burden and new treatment options. The authors also acknowledge many years of constant support and inspiration from family organizations such as the European Leukodystrophy Association, the Myelin Project, the Adrenoleukodystrophy (ALD) Charity, the Stop ALD Foundation and the United Leukodystrophy Foundation. W.K. received funding from the German Ministry of Education and Research as part of the German LEUKONET Network.
The authors declare no competing financial interests.
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Köhler, W., Curiel, J. & Vanderver, A. Adulthood leukodystrophies. Nat Rev Neurol 14, 94–105 (2018). https://doi.org/10.1038/nrneurol.2017.175
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