Biochemical and Molecular Biology Laboratory, Metabolic Inborn Errors of Metabolism Unit, Groupement Hospitalier Est, CHU de Lyon, Bron, France.
National Reference Centre for Hereditary Metabolic Diseases, Groupement Hospitalier Est, CHU de Lyon, Bron, France.
J Inherit Metab Dis. 2023 Sep;46(5):848-873. doi: 10.1002/jimd.12664.
Since the identification of the first disorder of mitochondrial fatty acid oxidation defects (FAOD) in 1973, more than 20 defects have been identified. Although there are some differences, most FAOD have similar clinical signs, which are mainly due to energy depletion and toxicity of accumulated metabolites. However, some of them have an unusual clinical phenotype or specific clinical signs. This manuscript focuses on what we have learnt so far on the pathophysiology of these disorders, which present with clinical signs that are not typical of categorical FAOD. It also highlights that some disorders have not yet been identified and tries to make assumptions to explain why. It also deals with new treatments under consideration in FAOD, including triheptanoin and similar anaplerotic substrates, ketone body treatments, RNA and gene therapy approaches. Finally, it suggests challenges for the diagnosis of FAOD in the coming years, both for symptomatic patients and for those diagnosed through newborn screening. The ultimate goal would be to identify all the patients born with FAOD and ensure for them the best possible quality of life.
自 1973 年首次发现线粒体脂肪酸氧化缺陷（FAOD）疾病以来，已经鉴定出 20 多种缺陷。尽管存在一些差异，但大多数 FAOD 具有相似的临床特征，主要是由于能量耗竭和累积代谢物的毒性。然而，其中一些具有不寻常的临床表型或特定的临床特征。本文重点介绍了迄今为止我们对这些疾病病理生理学的了解，这些疾病的临床表现与典型的 FAOD 不同。它还强调了一些尚未被发现的疾病，并试图解释原因。它还涉及 FAOD 中正在考虑的新治疗方法，包括三庚酸和类似的补料底物、酮体治疗、RNA 和基因治疗方法。最后，它对未来几年 FAOD 的诊断提出了挑战，包括有症状的患者和通过新生儿筛查诊断的患者。最终目标是识别所有出生时患有 FAOD 的患者，并为他们提供尽可能好的生活质量。
