title: Severe sensory neuropathy in patients with adult-onset multiple acyl-CoA dehydrogenase deficiency.
abstract: Multiple Acyl-CoA dehydrogenase deficiency (MADD) is an autosomal recessive disorder of fatty acid oxidation. Most patients with late-onset MADD are clinically characterized by lipid storage myopathy with dramatic responsiveness to riboflavin treatment. Abnormalities of peripheral neuropathy have rarely been reported in patients with late-onset MADD. We describe six patients who presented with proximal limb weakness and loss of sensation in the distal limbs. Muscle biopsy revealed typical myopathological patterns of lipid storage myopathy and blood acylcarnitine profiles showed a combined elevation of multiple acylcarnitines supporting the diagnosis of MADD. However, nerve conduction investigations and sural nerve biopsies in these patients indicated severe axonal sensory neuropathy. Causative ETFDH gene mutations were found in all six cases. No other causative gene mutations were identified in mitochondrial DNA and genes associated with hereditary neuropathies through next-generation-sequencing panel. Late-onset patients with ETFDH mutations can present with proximal muscle weakness and distal sensory neuropathy, which might be a new phenotypic variation, but the precise underlying pathogenesis remains to be elucidated.
authors.affiliation: Department of Neurology, Peking University First Hospital, Beijing, China.
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Nanchang University, Nanchang, China.
authors.forename: Daojun
authors.initials: D
authors.lastname: Hong
authors.affiliation: Department of Neurology, Peking University First Hospital, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
authors.forename: Wurong
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Neurology, Peking University First Hospital, Beijing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Shi
authors.affiliation: Department of Neurology, Peking University First Hospital, Beijing, China.
authors.forename: Danhua
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Department of Neurology, The Central Hospital of China Aerospace Corporation, Beijing, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Neurology, Peking University First Hospital, Beijing, China.
authors.forename: He
authors.initials: H
authors.lastname: Lv
authors.affiliation: Department of Neurology, Peking University First Hospital, Beijing, China. Electronic address: yuanyun2002@sohu.com.
authors.forename: Yun
authors.initials: Y
authors.lastname: Yuan
mesh_terms: D000328:Adult; D017668:Age of Onset; D044927:Electron-Transferring Flavoproteins / Q000235:genetics*; D005260:Female; D006801:Humans; D007506:Iron-Sulfur Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D054069:Multiple Acyl Coenzyme A Dehydrogenase Deficiency / Q000097:blood / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D009154:Mutation; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*; D010523:Peripheral Nervous System Diseases / Q000097:blood / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D010641:Phenotype
chemical_list: D044927:Electron-Transferring Flavoproteins; D007506:Iron-Sulfur Proteins; D000587:Oxidoreductases Acting on CH-NH Group Donors; C023120:electron-transferring-flavoprotein dehydrogenase
keywords: ETFDH; Multiple Acyl-CoA dehydrogenase deficiency; Phenotype; Sensory neuropathy