Gottfried Schatz Research Center, Molecular Biology and Biochemistry, Medical University of Graz, 8010 Graz, Austria.
Gottfried Schatz Research Center, Molecular Biology and Biochemistry, Medical University of Graz, 8010 Graz, Austria.
Trends Mol Med. 2023 Jun;29(6):425-438. doi: 10.1016/j.molmed.2023.03.001. Epub 2023 Apr 5.
Lysosomal acid lipase (LAL) is the sole enzyme known to degrade neutral lipids in the lysosome. Mutations in the LAL-encoding LIPA gene lead to rare lysosomal lipid storage disorders with complete or partial absence of LAL activity. This review discusses the consequences of defective LAL-mediated lipid hydrolysis on cellular lipid homeostasis, epidemiology, and clinical presentation. Early detection of LAL deficiency (LAL-D) is essential for disease management and survival. LAL-D must be considered in patients with dyslipidemia and elevated aminotransferase concentrations of unknown etiology. Enzyme replacement therapy, sometimes in combination with hematopoietic stem cell transplantation (HSCT), is currently the only therapy for LAL-D. New technologies based on mRNA and viral vector gene transfer are recent efforts to provide other effective therapeutic strategies.
溶酶体酸性脂肪酶 (LAL) 是唯一已知能够降解溶酶体中中性脂质的酶。编码 LAL 的 LIPA 基因突变导致罕见的溶酶体脂质贮积症，LAL 活性完全或部分缺失。本综述讨论了缺陷 LAL 介导的脂水解对细胞脂质动态平衡、流行病学和临床表现的影响。早期发现 LAL 缺乏症 (LAL-D) 对于疾病管理和生存至关重要。对于血脂异常和不明原因的氨基转移酶浓度升高的患者，必须考虑 LAL-D。酶替代疗法，有时联合造血干细胞移植 (HSCT)，是目前治疗 LAL-D 的唯一方法。基于 mRNA 和病毒载体基因转移的新技术是提供其他有效治疗策略的最新尝试。
