DARS2encodes mitochondrial aspartyl-tRNA synthetase. Nearly all patients are compound heterozygous; very often one allele is a splice-site variant in intron 2 that affects splicing of exon 3 in a cell-type-dependent manner. MRI shows inhomogeneous signal abnormalities of the cerebral white matter with characteristic involvement of the dorsal columns and lateral corticospinal tracts of the spinal cord, cerebellar peduncles and other brain stem tracts; MR spectroscopy can show elevated lactate in the abnormal white matter. The combination of clinical features and this MRI pattern is highly specific. Molecular diagnosis is established by demonstrating biallelic pathogenic DARS2variants; enzyme activity can be assayed in lymphoblasts.
DARS2