EP.04A case of late onset multiple acyl-CoA dehydrogenase deficiency with novel ETFDH mutation

Abstract

Multiple acyl-CoA dehydrogenase deficiency (MADD) is a rare disorder of fatty acid and amino acid metabolism characterized by muscle weakness, metabolic acidosis, hepatic dysfunction and encephalopathy. MADD is difficult to diagnose because of its wide range of clinical manifestations. Herein, we report a case of late onset MADD with novel ETFDH gene mutation. A 17-year-old female visited our clinic due to progressive 4-extremity weakness developed 6 months ago. She complained of myalgia and dyspnea. Neurologic examination revealed proximal dominant weakness, which was more severe on the upper extremities. Electromyography showed myopathic patterns. Serum glucose level was low and initial CK level was highly elevated to 5,720 IU/L. Muscle biopsy showed nonspecific myopathic changes with mild mitochondrial abnormality on the electron microscopy. Acid-alpha glucosidase level was normal. After admission, her dyspnea was gradually worsened and she was treated in the ICU after tracheostomy. She showed recurrent generalized tonic-clonic seizure and was treated with antiepileptic drugs. In suspicion of metabolic disease, we screened urine organic acid. Many organic acids levels including glutaric acid, ethylmalonic acid, glycine were increased. The genetic study revealed novel heterogenous mutation in ETFDH gene. She was finally diagnosed as MADD. After flavoprotein supplementation, her symptoms are slowing improving. MADD is an autosomal recessive inherited disease caused by mutations related with electron transfer to respiratory chain by flavoproteins. There is a possibility that it can be treated to some extent by flavoprotein supplementation. Therefore, MADD should be considered in patients with myopathy with progressive respiratory distress.