The emerging neurological spectrum of AARS2-associated disorders

Abstract Background The AARS2 gene encodes a mitochondrial alanyl-transfer RNA synthetase. Defects in this gene have been linked with autosomal recessive inheritance of a variety of different clinical phenotypes. Case A 13 year-old boy developed behavioral and psychiatric problems following a mild head injury. At age 21 he developed tremor, parkinsonism, and eye nystagmus. MRI revealed white matter changes consistent with a leukoencephalopathy. Genetic studies revealed two pathogenic mutations in the AARS2 gene (c.647dupG and c.595C > T). Literature review Only 47 cases of AARS2 -associated disorders have been reported, with equal numbers of males and females, and age at onset ranging from infancy to 44 years. The most common clinical problems include movement disorders (71%), cognitive impairment (67%), corticospinal signs (64%), behavioral or psychiatric features (46%), and eye signs (34%). Imaging evidence suggestive of leukoencephalopathy is common, but not invariant. Premature ovarian failure is frequent in females, but not universal. Conclusions Defects in the AARS2 gene are a rare cause for a variety of movement disorders, often associated with brain imaging evidence suggestive of leukoencephalopathy.