Leukoencephalopathy due to autosomal recessive mutations in the mitochondrial alanyl-transfer RNA (tRNA) synthetase gene (AARS2-L) refers to a rare, adult-onset leukodystrophy ¹. AARS2-L strongly resembles adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP).

Epidemiology

Compared to ALSP, AARS2-L is even rarer and tends to present at a younger age, with a mean age of 26 years (14 to 44 years according to one study) ².

Clinical presentation

Cognitive findings are invariably present and accompanied by motor and gait disturbances. Ovarian failure is seen in all female patients ^1,2.

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 ². 

Radiographic features

AARS2-L strongly resembles ALSP on imaging, but there are subtle differences ^2-4.

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

There exists no accepted specific therapy and thus treatment is supportive ⁵.

Differential diagnosis

• adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP)