摘要：Mitochondrial trifunctional protein (TFP) deficiency is a rare inherited metabolic disorder caused by defects in fatty acid β-oxidation (FAO) of long-chain fatty acids, leading to impaired energy production. Fasting avoidance, fatty acid-restricted diets, and supplementation with medium-chain triglycerides are recommended as a treatment, but there are no pharmaceutical treatments available with strong evidence of efficacy. Bezafibrate, which enhances the transcription of FAO enzymes, is a promising therapeutic option for FAO disorders (FAODs). The effectiveness of bezafibrate for FAODs has been reported in some clinical trials, but few clinical studies have investigated its in vivo efficacy toward TFP deficiency. Herein, we describe two Japanese patients with TFP deficiency. Patient 1 presented with recurrent myalgia since the age of 5 years. Laboratory findings showed increased serum levels of long-chain fatty acids and reduced expression of TFPα and TFPβ in his skin fibroblasts. Based on these findings, he was diagnosed with the myopathic type of TFP deficiency. Patient 2 suddenly exhibited cardiopulmonary arrest one day after birth. Elevated levels of creatine kinase and long-chain acylcarnitines were observed. Genetic analysis identified compound heterozygous variants in HADHB (c.1175C>T/c.1364T>G). He was diagnosed with the lethal type of TFP deficiency. Although both patients were treated with dietary therapy and l -carnitine supplementation, they experienced frequent myopathic attacks associated with respiratory infections and exercise. After the initiation of bezafibrate, their myopathic manifestations were markedly reduced, leading to an improvement in quality of life without any side effects. Our clinical findings indicate that bezafibrate combined with other treatments such as dietary therapy may be effective in improving myopathic manifestations in TFP deficiency.
关键词：Bezafibrate ; TFP deficiency ; Myalgia ; Rhabdomyolysis ; Fatty acid β-oxidation disorders (FAODs) ; l -carnitine ; TFP trifunctional protein ; FAO fatty acid β-oxidation ; FAODs fatty acid β-oxidation disorders ; VLCAD very-long-chain acyl-CoA dehydrogenase ; LCHAD long-chain 3-hydroxyacyl-CoA dehydrogenase ; MCT medium-chain triglycerides ; CPT2 carnitine palmitoyltransferase II ; CK creatine kinase ; AST aspartate aminotransferase ; ALT alanine aminotransferase ; CPA cardiopulmonary arrest ; QOL quality of life
