LBSL is caused by biallelic pathogenic variants in DARS2, encoding mitochondrial aspartyl-tRNA synthetase (mtAspRS). Fewer than 100 patients have been published, but the disease is probably underdiagnosed. Inheritance is autosomal recessive.
Onset is typically in late childhood or adolescence with slowly progressive cerebellar ataxia, spasticity and dorsal column dysfunction. The phenotypic spectrum is broad, ranging from a severe antenatal/neonatal presentation with profound developmental delay and early death to mild adult-onset disease. The diagnosis rests on a highly characteristic MRI pattern combined with genetic confirmation.
DARS2