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.

线粒体三功能蛋白（TFP）缺乏症是一种罕见的遗传性代谢紊乱，由长链脂肪酸的脂肪酸β-氧化（FAO）缺陷引起，导致能量产生受损。建议避免饮食，禁食脂肪酸和补充中链甘油三酸酯作为治疗方法，但是目前尚无有效的药物治疗方法。苯扎贝特可增强粮农组织酵素的转录，是解决粮农组织疾病（FAOD）的一种有前途的治疗选择。在一些临床试验中已经报道了苯扎贝特对FAOD的有效性，但是很少有临床研究调查其对TFP缺乏症的体内功效。

在这里，我们描述了两名日本人TFP缺乏症。自1岁起，患者1出现了复发性肌痛。实验室检查结果显示，他的皮肤成纤维细胞血清中长链脂肪酸水平升高，TFPα和TFPβ表达降低。基于这些发现，他被诊断出患有TFP缺乏症的肌病型。患者2在出生后一天突然出现心肺骤停。观察到肌酸激酶和长链酰基肉碱水平升高。遗传分析鉴定了HADHB中的复合杂合变体（c.1175C> T / c.1364T> G）。他被诊断为致命性TFP缺乏症。虽然这两个患者进行饮食疗法和治疗升补充肉碱后，他们经常发生与呼吸道感染和运动有关的肌病发作。苯扎贝特开始治疗后，它们的肌病表现显着降低，从而改善了生活质量，而没有任何副作用。

我们的临床发现表明，苯扎贝特与其他治疗方法（如饮食疗法）结合可以有效改善TFP缺乏症的肌病表现。