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Neurology. 2015 Jan 20;84(3):226-30. doi: 10.1212/WNL.0000000000001157. Epub 2014 Dec 19.

DARS-associated leukoencephalopathy can mimic a steroid-responsive neuroinflammatory disorder.

Author information

1
From 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.
2
From 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.

Abstract

OBJECTIVE:

To describe the expanding clinical spectrum of a recently described hereditary leukoencephalopathy, hypomyelination with brainstem and spinal cord involvement and leg spasticity, which is caused by mutations in the aspartyl tRNA-synthetase encoding gene DARS, including patients with an adolescent onset.

METHODS:

Three patients with mutations in DARS were identified by combining MRI pattern recognition and genetic analysis.

RESULTS:

One patient had the typical infantile presentation, but 2 patients with onset in late adolescence had a disease mimicking an acquired inflammatory CNS disorder. Adolescent-onset patients presented with subacute spastic paraplegia and had positive response to steroids. They had only minor focal supratentorial white matter abnormalities, but identical spinal cord changes involving dorsal columns and corticospinal tracts. Clinical presentation included subacute spastic paraplegia with partial improvement on steroids.

CONCLUSIONS:

Focal T2 hyperintense white matter changes on brain MRI in combination with spinal cord signal abnormalities usually suggest acquired inflammatory conditions such as multiple sclerosis, especially in the context of relapsing course and a positive response to steroid treatment. Adolescents with mutations in DARS can present with a comparable clinical picture, broadening the clinical spectrum of hypomyelination with brainstem and spinal cord involvement and leg spasticity.

PMID:
25527264
PMCID:
PMC4335995
DOI:
10.1212/WNL.0000000000001157
[Indexed for MEDLINE]
Free PMC Article

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