<i>DARS</i>
            -associated leukoencephalopathy can mimic a steroid-responsive neuroinflammatory disorder

Wolf, Nicole I.; Toro, Camilo; Kister, Ilya; Latif, Kartikasalwah Abd; Leventer, Richard J.; Pizzino, Amy; Simons, Cas; Abbink, Truus E.M.; Taft, Ryan J.; Knaap, Marjo S. van der; Vanderver, Adeline

doi:10.1212/wnl.0000000000001157

Cited by 64 publications

(75 citation statements)

References 11 publications

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“…The disease, called hypomyelination with brainstem and spinal involvement and leg spasticity, was initially reported in children,9 but an adult patient with subacute-onset spastic paraplegia and partial responsiveness to steroid was described, suggesting that DARS -related disease may mimic an acquired inflammatory disease 10…”

Section: Genetic and Metabolic Causes Of Medullary Signal Alterationsmentioning

confidence: 99%

Spinal cord involvement in adult-onset metabolic and genetic diseases

Marelli

Salsano

Politi

et al. 2018

J Neurol Neurosurg Psychiatry

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In adulthood, spinal cord MRI abnormalities such as T2-weighted hyperintensities and atrophy are commonly associated with a large variety of causes (inflammation, infections, neoplasms, vascular and spondylotic diseases). Occasionally, they can be due to rare metabolic or genetic diseases, in which the spinal cord involvement can be a prominent or even predominant feature, or a secondary one. This review focuses on these rare diseases and associated spinal cord abnormalities, which can provide important but over-ridden clues for the diagnosis. The review was based on a PubMed search (search terms: 'spinal cord' AND 'leukoencephalopathy' OR 'leukodystrophy'; 'spinal cord' AND 'vitamin'), further integrated according to the authors' personal experience and knowledge. The genetic and metabolic diseases of adulthood causing spinal cord signal alterations were identified and classified into four groups: (1) leukodystrophies; (2) deficiency-related metabolic diseases; (3) genetic and acquired toxic/metabolic causes; and (4) mitochondrial diseases. A number of genetic and metabolic diseases of adulthood causing spinal cord atrophy without signal alterations were also identified. Finally, a classification based on spinal MRI findings is presented, as well as indications about the diagnostic work-up and differential diagnosis. Some of these diseases are potentially treatable (especially if promptly recognised), while others are inherited as autosomal dominant trait. Therefore, a timely diagnosis is needed for a timely therapy and genetic counselling. In addition, spinal cord may be the main site of pathology in many of these diseases, suggesting a tempting role for spinal cord abnormalities as surrogate MRI biomarkers.

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Section: Genetic and Metabolic Causes Of Medullary Signal Alterationsmentioning

confidence: 99%

Spinal cord involvement in adult-onset metabolic and genetic diseases

Marelli

Salsano

Politi

et al. 2018

J Neurol Neurosurg Psychiatry

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“…Mutations in this gene have been found in patients who exhibit hypomyelination with brainstem and spinal cord involvement and leg spasticity [21, 22]. Homsy et al [23] used exome sequencing analysis in 1,213 CHD parent-offspring trios to identify several protein-damaging de novo mutations, particularly in genes that are highly expressed in the developing heart and brain.…”

Section: Discussionmentioning

confidence: 99%

Association of DARS gene polymorphisms with the risk of isolated ventricular septal defects in the Chinese Han population

Feng

Chen

2016

Ital J Pediatr

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BackgroundVentricular septal defects (VSD) are the most common subtype of congenital heart defects (CHD) and are estimated to account for 20 to 30% of all cases of CHD. The etiology of isolated VSD remains poorly understood. Eight core aminoacyl-tRNA synthetases (ARSs) (EPRS, MARS, QARS, RARS, IARS, LARS, KARS, and DARS) combine with three nonenzymatic components to form a complex known as the multisynthetase complex (MSC). Four single nucleotide polymorphisms (SNPs) in EPRS have been reported to be associated with risks of CHD in Chinese populations.MethodsIn this study, we hypothesize that SNPs of the DARS gene might influence susceptibility to sporadic isolated VSD. Therefore, we conducted a case-control study of 841 patients with isolated VSD and 2953 non-CHD controls from the Chinese Han population to evaluate how 4 potentially functional SNPs within the DARS gene were associated with the risk of VSD.ResultsWe observed that the risk of VSD was significantly associated with rs2164331 [G/A; odds ratio (OR) = 0.78, 95% confidence interval (CI) = 0.69-0.91; P = 3.17 × 10-3], rs6738266 [G/A; OR = 1.17, 95% CI = 1.05-1.29, P = 1.83 × 10-3], and rs309143 [G/A; OR = 1.09, 95% CI = 1.01-1.17; P = 3.12 × 10-2]. Additionally, compared with individuals with 0-2 risk alleles, individuals carrying 3, 4, and 5 or more risk alleles had 1.01-, 1.22- and 1.46-fold greater risks of VSD, respectively. These findings revealed a significant dose-response effect for VSD risk among individuals carrying different numbers of risk alleles (Ptrend = 6.37 × 10-4).ConclusionsThese findings indicate that genetic variants of the DARS gene may influence individual susceptibility to isolated VSD in the Chinese Han population.

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“…On the other hand, LARS is not linked to T2DM like LARS2. Instead, LARS endorses homozygous missense mutation in infantile hepatopathy, a life-threatening liver-disorder [84]. That apart, CharcotMarie-Tooth, CMT, disease has a widespread association to many ARS mutations.…”

Section: Ars/ars2 Gene Mutation Causing Diseasesmentioning

confidence: 99%