Leukoencephalopathy due to autosomal recessive mutations in the mitochondrial alanyl-transfer RNA (tRNA) synthetase gene (AARS2-L)
Leukoencephalopathy due to autosomal recessive mutations in the mitochondrial alanyl-transfer RNA (tRNA) synthetase gene (AARS2-L) refers to a rare, adult-onset leukodystrophy . AARS2-L strongly resembles adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP).
Epidemiology
Compared to ALSP, AARS2-L is even more rare and tends to present at a younger age with a mean age of 26 years (14 to 44 years according to one study) .
Clinical presentation
Cognitive findings are invariably present and accompanied by motor and gait disturbances. Ovarian failure is seen in all female patients.
Pathology
Histopathologic findings are near-identical to those in ALSP. Therefore, a brain biopsy in the absence of the correct genetic test may be misleading.
Radiographic features
AARS2-L strongly resembles ALSP on imaging, but there are subtle differences .
CT
White matter calcifications, while often seen in ALSP, are not seen in AARS2-L.
MRI
Like ALSP, AARS2-L presents with brain volume loss and hyperintense changes on FLAIR and DWI in the periventricular and subcortical white matter. Compared to the more ’band- and dot-like’ white matter changes in patients with ALSP, white matter signal abnormalities typically appear more confluent in AARS2-L. The corpus callosum is always involved, and the pyramidal tracts also are more often involved than in ALSP. Atrophy is present to a lesser degree than in ALSP and the corpus callosum shows milder thinning.
- T2/FLAIR: hyperintense
- DWI: persistent DWI hyperintense white matter lesions are a typical finding, and, as opposed to ALSP, occur in all patients
- T1: affected areas are low in signal
- T1 C+ (Gd): no enhancement is visible
Treatment and prognosis
Currently, there exists no accepted specific therapy and thus treatment is supportive .
Differential diagnosis
