Mutations in the HADHB gene lead to Mitochondrial Trifunctional Protein (MTP) deficiency. MTP deficiency is a rare autosomal recessive disorder affecting long-chain fatty acid oxidation. Patients affected by MTP deficiency are unable to metabolize long-chain fatty-acids and suffer a variety of symptoms exacerbated during fasting. The three phenotypes associated with complete MTP deficiency are an early-onset cardiomyopathy and early death, an intermediate form with recurrent hypoketotic hypoglycemia and a sensorimotor neuropathy with episodic rhabdomyolysis with small amount of residual enzyme activities. This review aims to discuss the pathophysiological mechanisms and clinical manifestations of each phenotype, which appears different and linked to HADHB expression levels. Notably, the pathophysiology of the sensorimotor neuropathy is relatively unknown and we provide a hypothesis on the qualitative aspect of the role of acylcarnitine buildup in Schwann cells in MTP deficiency patients. We propose that acylcarnitine may exit the Schwann cell and alter membrane properties of nearby axons leading to axonal degeneration based on recent findings in different metabolic disorders.

HADHB 基因突变导致线粒体三功能蛋白 (MTP) 缺乏。MTP缺乏症是一种罕见的常染色体隐性遗传病，影响长链脂肪酸氧化。受 MTP 缺乏影响的患者无法代谢长链脂肪酸，并且在禁食期间会出现多种症状。与完全 MTP 缺乏相关的三种表型是早发性心肌病和早死、复发性低酮性低血糖的中间型和伴有少量残留酶活性的偶发性横纹肌溶解的感觉运动神经病。本综述旨在讨论每个表型的病理生理机制和临床表现，这些表型似乎不同并与 HADHB 表达水平有关。值得注意的是，感觉运动神经病的病理生理学相对未知，我们提供了一个关于酰基肉碱积聚在 MTP 缺乏患者雪旺细胞中作用的定性方面的假设。根据最近在不同代谢紊乱中的发现，我们提出酰基肉碱可能会离开雪旺氏细胞并改变附近轴突的膜特性，导致轴突变性。