Folate metabolism disorder presenting as an opticospinal syndrome

Opticospinal syndrome (concurrent involvement of the optic nerve and spinal cord) in young adults is usually caused by an immune-mediated disease, such as multiple sclerosis, neuromyelitis optica spectrum disorder or myelin oligodendrocyte glycoprotein antibody-associated disease. These conditions typically respond to corticosteroids and follow a relapsing-remitting course. We report a man with opticospinal syndrome, who initially appeared steroid-responsive, but was subsequently found to have a pathogenic mutation in the methylenetetrahydrofolate reductase ( MTHFR ) gene, causing folate deficiency and associated neurological complications. Skin hyperpigmentation had suggested a metabolic cause, such as adrenoleukodystrophy or a disorder of cobalamin metabolism. Importantly, steroid responsiveness alone is not diagnostic for inflammatory and demyelinating disorders.