Open AccessAARS 2 leukoencephalopathy: A new variant of mitochondrial encephalomyopathy
Author(s) -
Tang Yi,
Qin Qi,
Xing Yi,
Guo Dongmei,
Di Li,
Jia Jianping
Publication year - 2019
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.582
Subject(s) - leukoencephalopathy , medicine , ataxia , white matter , pathology , corticospinal tract , mitochondrial encephalomyopathy , magnetic resonance imaging , mutation , biology , genetics , disease , gene , radiology , psychiatry , diffusion mri
Background Mutations in the mitochondrial alanyl‐transfer (t) RNA synthetase 2 ( AARS 2 , OMIM :612035) have been linked to leukoencephalopathy recently. Till now, there have been 19 cases reported so far. However, the clinical and genetic characteristics of this disease are not fully understood. We reported an adult‐onset male leukoencephalopathy patient related to novel AARS 2 gene mutations and reviewed all previous cases regarding the clinical and genetic features of AARS 2 leukoencephalopathy. Methods The spectrum of clinical symptoms and the genetic analysis of the presented patient were identified and investigated. Besides this case, we assessed previously reported cases with AARS 2 gene mutations. Results Here, we present a 30‐year‐old man with progressive motor deficits in the right lower limb and severe cerebellar ataxia for one year. MRI revealed extensive white matter lesions in periventricular regions and along the corticospinal tract. Genetic analysis revealed two new heterogeneous missense mutations in AARS 2 : c.179C>A and c.1703_1704del. We described the ragged red fiber ( RRF ) for the first time, suggesting that AARS 2 ‐related leukoencephalopathy be a new variant of mitochondrial encephalomyopathy. Gradual improvement in motor function was observed with intravenous coenzyme complex treatment. We also summarized our case and all previously reported cases to provide an overview of AARS 2 ‐related late‐onset leukoencephalopathy. Then, we compared clinical and neuroimaging features of AARS 2 ‐related leukoencephalopathy with three other frequently diagnosed types of adult‐onset leukoencephalopathy to provide insight into diagnostic strategies. Conclusion The characteristic MRI abnormalities and clinical symptoms described here may help to distinguish AARS 2 ‐related leukoencephalopathy from other adult‐onset leukoencephalopathies. The combination of encephalopathy and myopathy strongly suggest that AARS 2 ‐related leukoencephalopathy is a new variant of mitochondrial encephalomyopathy. The response to coenzyme complex will shed light on future therapy investigation.