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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is a recently described disorder with autosomal recessive model of inheritance. Mutations in the DARS2 gene, which encode mitochondrial aspartyl-tRNA synthetase, have been found. We present 31 cases with characteristic clinical and neuroimaging findings of this disorder. Patients have been stratified into two groups (early and late forms) by age-at-onset and clinical symptoms. The early form was characterized clinically by progressive pyramidal dysfunction, cerebellar and intellectual problems appeared later. Patients with the late form had cerebellar and sensitive ataxia, disturbances of muscle tonus, spastic type, mostly in the low extremities, polyneuropathic and rarely - psychoorganic syndrome. The brain MRI of all patients was characterized by inhomogeneous T2W signal abnormalities in the periventricular and deep white matter and a strikingly selective involvement of certain brainstem and spinal tracts. Most of the patients were compound-heterozygous for common mutations in the DARS2. We found 4 new mutations associated with LBSL. This is the first clinical and molecular-genetic investigation of this rare leukoencephalopathy in Russia.
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PMID:[Clinical and molecular genetic diagnosis of leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation in children]. 1977 Aug 27

Leukoencephalopathy with brainstem and spinal cord involvement and elevated lactate (LBSL) is a rare, autosomal recessive disorder caused by mutations in the gene encoding a mitochondrial aspartyl-tRNA synthetase, DARS2. The disease is characterized by progressive spastic ataxia and magnetic resonance imaging (MRI) shows a highly characteristic leukoencephalopathy with multiple long tract involvement. We describe the clinical and radiological features of two new cases of LBSL and report a novel pathogenic mutation in the DARS2 gene. Both patients had typical clinical and radiological findings, although no elevated lactate was found. The severity of MRI changes did not correlate with clinical course and severity suggesting that, although of highly specific diagnostic value, MRI does not necessarily reflect clinical activity and should not be used to assess disease severity or prognosis in LBSL.
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PMID:Leukoencephalopathy with brainstem and spinal cord involvement caused by a novel mutation in the DARS2 gene. 2179 30

Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation is a rare disorder caused by mutations in the gene encoding a mitochondrial aspartyl-tRNA synthetase, DARS2. Clinical features include childhood or adolescent onset, slowly progressive ataxia, spasticity, and dorsal column dysfunction with or without mild cognitive decline. Magnetic resonance (MR) images show a characteristic leukoencephalopathy with multiple long tract involvement. MR spectroscopy shows elevated levels of lactate. We present strikingly different clinical courses and discrepant MR images findings for a pair of brothers. It cannot be excluded that in the cases presented, the different clinical outcome is related to a varicella infection in infancy in the younger brother.
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PMID:Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation: high outcome variation between two siblings. 2440 72

Although mitochondria are ubiquitous, each mitochondrial disease has surprisingly distinctly different pattern of tissue and organ involvement. Congruently, mutations in genes encoding for different mitochondrial tRNA synthetases result in the development of a very flamboyant group of diseases. Mutations in some of these genes, including aspartyl-tRNA synthetase (DARS2), lead to the onset of a white matter disease-leukoencephalopathy with brainstem and spinal cord involvement, and lactate elevation (LBSL) characterized by progressive spastic ataxia and characteristic leukoencephalopathy signature with multiple long-tract involvements. Puzzled by the white matter disease phenotypes caused by DARS2 deficiency when numerous other mutations in the genes encoding proteins involved in mitochondrial translation have a detrimental effect predominantly on neurons, we generated transgenic mice in which DARS2 was specifically depleted in forebrain-hippocampal neurons or myelin-producing cells. Our results now provide the first evidence that loss of DARS2 in adult neurons leads to strong mitochondrial dysfunction and progressive loss of cells. In contrast, myelin-producing cells seem to be resistant to cell death induced by DARS2 depletion despite robust respiratory chain deficiency arguing that LBSL might originate from the primary neuronal and axonal defect. Remarkably, our results also suggest a role for early neuroinflammation in the disease progression, highlighting the possibility for therapeutic interventions of this process.
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PMID:DARS2 protects against neuroinflammation and apoptotic neuronal loss, but is dispensable for myelin producing cells. 2898 37