Rinsho Shinkeigaku (Clinical Neurology)

Case Report

Mitochondrial trifunctional protein deficiency: an adult patient with similar progress to Charcot-Marie-Tooth disease

Yuki Yamamoto, M.D.1), Naoko Matsui, M.D.1), Yu Hiramatsu, M.D.2), Yoshimichi Miyazaki, M.D.1)3), Hiroyuki Nodera, M.D.1), Yuishin Izumi, M.D.1), Hiroshi Takashima, M.D.2) and Ryuji Kaji, M.D.1)

1)Department of Clinical Neuroscience, Institute of Biomedical Sciences, Tokushima University Graduate School
2)Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences
3)Department of Neurology, Hyogo Prefectural Awaji Medical Center

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.
Full Text of this Article in Japanese PDF (905K)

(CLINICA NEUROL, 57: 82－87, 2017)
key words: mitochondrial trifunctional protein (MTP) deficiency, HADHB gene, long-chain fatty acid, peripheral neuropathy, rhabdomyolysis

(Received: 25-Oct-16)