title: Mitochondrial trifunctional protein deficiency: an adult patient with similar progress to Charcot-Marie-Tooth disease.
abstract: A 45-year-old man presented to us due to slowly progressive muscle weakness and sensory disturbances in his lower limbs since his 40's. He reported multiple episodes of exercise-induced severe muscle fatigue and brown urine in his childhood, which disappeared by age 20. A nerve conduction study showed peripheral axonal neuropathy and then Charcot-Marie-Tooth disease (CMT) was considered as the most likely diagnosis; however, exome sequencing failed to identify a mutation in the known genes of CMTs. Since age 55, he recurrently developed severe rhabdomyolysis that required hospitalization. On suspicion of lipid metabolism disorders, we performed serum acylcarnitine analysis, and which revealed mildly elevated long-chain fatty acids. We re-examined variants obtained via exome sequencing and found a mutation in HADHB. Mitochondrial trifunctional protein (MTP) deficiency is a rare autosomal recessive disorder of mitochondrial fatty acid beta-oxidation caused by HADHA or HADHB mutation. It can be a life-threatening multiorgan disorder with early infantile onset, but it can also present in childhood or adolescence with peripheral neuropathy and recurrent rhabdomyolysis. This case of adult-diagnosed MTP deficiency was characterized by slowly progressive peripheral neuropathy masquerading CMT in addition to muscular symptoms. MTP deficiency should be considered in patients with the combination of peripheral neuropathy and recurrent rhabdomyolysis.
authors.affiliation: Department of Clinical Neuroscience, Institute of Biomedical Sciences, Tokushima University Graduate School.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Naoko
authors.initials: N
authors.lastname: Matsui
authors.forename: Yu
authors.initials: Y
authors.lastname: Hiramatsu
authors.forename: Yoshimichi
authors.initials: Y
authors.lastname: Miyazaki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nodera
authors.forename: Yuishin
authors.initials: Y
authors.lastname: Izumi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takashima
authors.forename: Ryuji
authors.initials: R
authors.lastname: Kaji
mesh_terms: D015415:Biomarkers / Q000097:blood; D009202:Cardiomyopathies / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D002331:Carnitine / Q000031:analogs & derivatives / Q000097:blood; D002607:Charcot-Marie-Tooth Disease; D003937:Diagnosis, Differential; D018450:Disease Progression; D005820:Genetic Testing; D006801:Humans; D008052:Lipid Metabolism, Inborn Errors / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D017240:Mitochondrial Myopathies / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D063991:Mitochondrial Trifunctional Protein / Q000172:deficiency* / Q000235:genetics; D063993:Mitochondrial Trifunctional Protein, beta Subunit / Q000235:genetics; D009154:Mutation; D009422:Nervous System Diseases / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D010523:Peripheral Nervous System Diseases / Q000209:etiology; D012008:Recurrence; D012206:Rhabdomyolysis / Q000150:complications / Q000175:diagnosis* / Q000209:etiology / Q000235:genetics
chemical_list: D015415:Biomarkers; C116917:acylcarnitine; C576206:HADHB protein, human; D063991:Mitochondrial Trifunctional Protein; D063993:Mitochondrial Trifunctional Protein, beta Subunit; D002331:Carnitine