Spinal Cord Involvement in Patients with Adult-Onset Multiple Acyl-CoA Dehydrogenase Deficiency

Riboflavin responsive multiple acyl-CoA dehydrogenase deficiency (RR-MADD) is an inherited metabolic disorder which is good responsive to riboflavin treatment. The phenotypic spectrum of adult-onset RR-MADD is highly heterogeneous. In this study, we described three patients with adult-onset RR-MADD presented with muscle weakness and spinal cord involvement. These three patients presented with adult-onset limb weakness, dyspnea, along with sensory levels changes (patient 1 below T2 level, patient 2 below T6 level, and patient 3 below T12 level, respectively). All patients displayed elevated acylcarnitine and urinary organic acids. Muscle biopsies in patient 1 and patient 2 revealed the presence of lipid vacuoles and COX-negative fibers. Genetic analysis identified ETFDH mutation (c.524G > A (p.R175H)) in patient 1, and a compound heterozygous ETFDH mutation (c.34G > C (p.A12P)/c.736G > A (p.E246K)) in patient 2. Spinal-cord MRI excluded structural lesions, whereas muscle MRI indicated fatty infiltration. Short-term riboflavin treatment proved effective in alleviating muscle weakness, while long-term administration of riboflavin, coenzyme Q10, and vitamin B12 demonstrated efficacy in alleviating spinal cord involvement. Inconclusion, our findings suggest that spinal cord involvement may manifest in certain patients with adult-onset RR-MADD, which expand the neurological spectrum of adult-onset RR-MADD.