Acquired Multiple Acyl‐Coenzyme A Dehydrogenase Deficiency Associated With Sertraline in Sweden—A Nationwide Population‐Based Study

BACKGROUND: Recent studies describe an association between sertraline and acquired late-onset multiple acyl coenzyme A dehydrogenase deficiency (MADD), a rare disorder affecting fatty acid metabolism. MADD was previously considered solely a genetic disorder caused by recessive pathogenic variants mainly in the ETFDH gene. METHODS: A nationwide population-based registry search was conducted to identify adult patients with sertraline-associated MADD in Sweden 2014-2024. Patients with muscle biopsy reports of lipid storage myopathy or biochemical investigations showing acylcarnitine profile suggesting MADD were included. Medical records were retrospectively reviewed. RESULTS: We identified 40 (30/10 female/male) patients using sertraline when diagnosed with MADD. Median age at symptom onset was 42 years and muscle weakness was the most common first symptom. All patients reported muscle symptoms during the disease course. Extra-muscular symptoms, including sensory disturbance (29 patients) and fatigue (18 patients), were common. Most had lipid accumulation in muscle fibers, an abnormal acylcarnitine profile, a myopathic electromyography pattern, and elevated creatine kinase. Cyanocobalamin, folic acid, and proton-pump inhibitors were the most frequent other medications at diagnosis. Five patients carried a heterozygous ETFDH variant. All patients were treated with riboflavin. Almost all (38/39) experienced clinical improvement. Acylcarnitine profile improved in all patients (31/31) with available data. The mean incidence was 1.24 patients per 100,000 adults receiving sertraline treatment per year. CONCLUSIONS: Acquired MADD associated with sertraline is the most common type of adult-onset MADD in Sweden. The disease is generally responsive to riboflavin treatment. Patients presenting with muscle symptoms during sertraline therapy should undergo adequate evaluation to exclude MADD.