Recent insights into lysosomal acid lipase deficiency

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 concen-trations of unknown etiology. Enzyme replacement therapy, sometimes in combina-tion 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.

Automated summary

Lysosomal acid lipase (LAL) is an essential enzyme for degrading neutral lipids in the lysosome. Mutations in the LAL-encoding LIPA gene can cause rare lysosomal lipid storage disorders, leading to reduced or absent LAL activity. This review discusses the impact of defective LAL-mediated lipid hydrolysis on cellular lipid homeostasis, epidemiology, and clinical presentation. Early detection of LAL deficiency (LAL-D) is crucial for disease management and survival. Enzyme replacement therapy, sometimes in combination with hematopoietic stem cell transplantation (HSCT), is currently the only therapy available for LAL-D. New technologies such as mRNA and viral vector gene transfer are being explored as potential therapeutic strategies.