EP.09Hypersomnia-featured very long-chain acyl-coenzyme a dehydrogenase deficiency caused by a homozygous R428H mutation of ACADVL

Abstract

Very long-chain acyl-coenzyme a dehydrogenase deficiency (VLCADD) is an autosomal recessive inherited disorder of mitochondrial fatty-acid β-oxidation. It can be severe infantile-onset cardiac, childhood-onset hypoglycemic, and adolescent/adult-onset myopathic. The myopathic VLCADD as shown in present patient usually presents with muscle pain and myoglobinuria after fasting or exercise, but to our knowledge, hypersomnia as a main symptom in any type of VLCADD has never been reported before. We report an unusual case involving a patient with hypersomnia. A 52-year-old man presented with recurrent myalgia, weakness, myoglobinuria and hypersomnia triggered by excessive exercise. Muscle pathology showed mild necrosis and regeneration. A homozygous mutation c. 1283G>A (p.R428H) in the very long chain acyl-coenzyme dehydrogenase (VLCAD) gene was found by next-generation sequencing, which has been proved pathogenic. Given that R428H mutation caused the loss of the catalytic ability of VLCAD and that the accumulation of acyl-carnitine reduces the carnitine level as a consequence of the defect of VLCAD, the impairment of the FAO process resulting in low level of free carnitine in VLCADD may plausibly explain the hypersomnia in our patient, though further studies are required for the molecular basis of the hypersomnia in VLCADD. Our report, therefore, broadens the phenotypic spectrum of VLCADD and suggests an awareness of VLCADD as a causative factor in the differential diagnosis and treatment of hypersomnia disorder.