Taking another look: LBSL diagnosed in adulthood masquerading as multiple sclerosis

Abstract

Background: Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is a rare autosomal recessive leukodystrophy typically diagnosed in early childhood and can mimic changes seen in demyelinating disorders. Objectives: To describe a case of LBSL diagnosed in adulthood presenting with mild neurological findings and abnormal neuroimaging, highlighting phenotypic variability and diagnostic challenges. Results: A woman in her 20s was referred for demyelinating disease based on white matter lesions on magnetic resonance imaging (MRI). She was found to have mild pyramidal signs and was diagnosed with LBSL following whole exome sequencing (WES)—biallelic likely pathogenic DARS2 variants (c.228-21_228-20delinsC and c.788G > A [p.Arg263Gln])—after an initially nondiagnostic leukodystrophy gene panel. Conclusions: This case illustrates LBSL can present in adulthood with relatively mild symptoms, radiographic features may overlap with demyelinating disease, and expanded genetic testing should be considered if the clinical suspicion is high despite initial non-diagnostic results.