Isolated peripheral neuropathy in a young adult: the role of comprehensive genetic testing

Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation is a disorder with an autosomal recessive mode of inheritance. It is caused by mutations of the DARS2 gene that encodes aspartyl-transfer RNA (tRNA) synthetase enzymes responsible for the accurate charging of aspartate-specific tRNA with aspartate. Clinical features include seizures, cognitive impairment, cerebellar signs, upper motor neuron type of weakness, peripheral neuropathy, muscle weakness, cramps and deformities. Exclusive involvement of the peripheral nervous system has not been reported so far. We describe a case in which the patient presented with peripheral neuropathy mimicking hereditary motor and sensory neuropathy type 1, and genetic analysis revealed a DARS2 mutation. This case highlights the potential phenotypic variability that can be associated with a DARS2 mutation and the importance of comprehensive genetic testing in unexplained neuropathies, while acknowledging the limitations, as it is a variant of uncertain significance. More research is necessary to establish definite causation.