Leukoencephalopathy caused by autosomal recessive mutations in the mitochondrial alanyl-tRNA synthetase gene (AARS2 leukoencephalopathy)
General description
Leukoencephalopathy caused by autosomal recessive mutations in the mitochondrial alanyl-tRNA synthetase gene, termed AARS2 leukoencephalopathy, is an adult-onset leukodystrophy that typically begins in the 20s to 30s.
Patients experience rapid deterioration following the onset of symptoms. Psychiatric manifestations, including changes in personality, delusions, anxiety, and depression, often precede neurological symptoms. Neurological dysfunctions consist of motor deterioration, characterized by cerebellar ataxia and pyramidal signs, along with progressive cognitive decline. The cognitive decline exhibits features of frontal lobe dysfunction, such as impaired attention, reduced activity, and other neurological changes, with cognitive decline being the most commonly reported symptom.
Differential diagnosis
The clinical manifestations and imaging findings of AARS2 leukoencephalopathy strongly resemble those of Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP). However, there are notable differences in imaging characteristics; for instance, white matter calcifications, often observed in ALSP, are not typically seen in AARS2 leukoencephalopathy. Unique to AARS2 leukoencephalopathy among leukodystrophies is the exclusive occurrence of ovarian failure, highlighting its distinct association with reproductive health issues.
White matter lesion
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CerebrumFrontal lobeCerebral white matter
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CerebrumParietal lobeCerebral white matter
In AARS2 leukoencephalopathy, bilateral hyperintensity in T2WI and FLAIR affecting the frontal and parietal lobes is commonly observed. Although Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) also presents with similar white matter hyperintensities, the pattern of lesions in ALSP is typically patchy. In contrast, AARS2 leukoencephalopathy exhibits a more diffuse or confluent pattern of lesions.
Corticospinal tract lesion
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Internal capsulePosterior limbCorticospinal tract
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Cerebral peduncleCorticospinal tract
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BrainstemPonsCorticospinal tract
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BrainstemMedullaCorticospinal tract
MRI findings in most cases show bilateral hyperintensity on T2WI and FLAIR sequences affecting the posterior limb of the internal capsule and the pyramidal tract of the brainstem.
Corpus callosum atrophy
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Corpus callosum
Cerebral atrophy
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Cerebrum
In AARS2 leukoencephalopathy, cerebral atrophy is observed but is typically milder compared to that seen in Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP).