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DARS-associated leukoencephalopathy can mimic a steroid-responsive neuroinflammatory disorder
Nicole I Wolf1, Camilo Toro2, Ilya Kister2
1From the Department of Child Neurology (N.I.W., T.E.M.A., M.S.v.d.K.), VU University Medical Center, Amsterdam; the Neuroscience Campus Amsterdam (N.I.W., T.E.M.A., M.S.v.d.K.), the Netherlands; the NIH Undiagnosed Diseases Program (C.T.), National Institutes of Health, Bethesda, MD; the NYU Multiple Sclerosis Center (I.K.), Department of Neurology, NYU School of Medicine, New York; the Department of Radiology (K.A.L.), Hospital Kuala Lumpur, Malaysia; the Department of Neurology (R.L.), Royal Children's Hospital; Murdoch Children's Research Institute (R.L.); the Department of Pediatrics (R.L.), University of Melbourne, Australia; the Department of Neurology (A.P., A.V.), Children's National Medical Center, Washington, DC; the Institute for Molecular Bioscience (C.S., R.J.T.), University of Queensland, St Lucia, Queensland, Australia; the Departments of Integrative Systems Biology and Pediatrics (R.J.T.), George Washington University School of Medicine, Washington, DC; Illumina Inc. (R.J.T.), San Diego, CA; and the Department of Functional Genomics (M.S.v.d.K.), Center for Neurogenomics and Cognitive Research, VU University, Amsterdam, the Netherlands. n.wolf@vumc.nl.
Hypomyelination with brainstem and spinal cord involvement and leg spasticity (HBSL) caused by DARS gene mutations can present in adolescents. These patients may mimic acquired inflammatory central nervous system disorders, responding to steroids.
Area of Science:
- Neurogenetics
- Neuroimmunology
- Leukodystrophy research
Background:
- Hypomyelination with brainstem and spinal cord involvement and leg spasticity (HBSL) is a rare hereditary leukoencephalopathy.
- Mutations in the aspartyl-tRNA synthetase (DARS) gene cause HBSL.
- The clinical spectrum of HBSL is still being defined.
Purpose of the Study:
- To delineate the expanding clinical spectrum of DARS-associated HBSL.
- To identify and characterize patients with adolescent-onset HBSL.
- To compare the presentation of infantile and adolescent-onset HBSL.
Main Methods:
- Case identification through MRI pattern recognition and genetic analysis.
- Clinical data collection and neuroimaging review.
- Analysis of genotype-phenotype correlations.
Main Results:
- One patient presented with typical infantile HBSL.
- Two adolescent-onset patients mimicked acquired inflammatory CNS disorders.
- Adolescent-onset HBSL featured subacute spastic paraplegia and responded to steroids, with distinct spinal cord and minor supratentorial white matter changes.
Conclusions:
- DARS mutations can cause HBSL with adolescent onset, presenting similarly to acquired inflammatory conditions like multiple sclerosis.
- Adolescent-onset HBSL broadens the known clinical spectrum of this leukodystrophy.
- MRI findings of white matter and spinal cord abnormalities in adolescents warrant consideration of genetic leukoencephalopathies.
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