Lessons Learned From the Long-Term Use of Enzyme Replacement Therapy in the Treatment of Lysosomal Acid Lipase Deficiency.
Lessons Learned From the Long-Term Use of Enzyme Replacement Therapy in the Treatment of Lysosomal Acid Lipase Deficiency.
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DOI：
10.1097/mpg.0000000000003453
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发表时间：
2022-06-01
影响因子：
2.9
通讯作者：
Ficicioglu, Can
中科院分区：
文献类型：
--
作者：
Strong, Alanna;Ficicioglu, Can
Lysosomal acid lipase deficiency (LALD, OMIM# 278000) is an inborn error of lipid metabolism caused by biallelic pathogenic variants in LIPA, which encodes the enzyme lysosomal acid lipase (LAL). LAL deficiency impairs the intra-lysosomal hydrolysis of cholesteryl esters and triglycerides, resulting in their intracellular accumulation. LAL deficiency also impairs liberation of free fatty acids and free cholesterol leading to perceived cholesterol paucity and inappropriate activation of de novo cholesterol biosynthesis and inhibition of cholesterol efflux (Fig. 1)(1). Disease severity is dictated by residual enzyme activity and ranges from infantile Wolman disease (WD) to cholesteryl ester storage disease (CESD). WD is characterized by failure to thrive, malabsorption, hepatosplenomegaly, cholestasis, elevated aminotransferases, hepatic fibrosis, and adrenal insufficiency and was historically fatal without bone marrow transplantation. CESD is characterized by childhood to adult-onset hepatomegaly, elevated aminotransferases, liver dysfunction, cirrhosis, dyslipidemia, premature atherosclerotic cardiovascular disease, and hepatocellular carcinoma (2, 3).In 2015, the Food and Drug Administration approved the enzyme replacement therapy (ERT) sebelipase alfa for the treatment of LALD. Early studies showed improved survival for infants with WD and improved dyslipidemia, aminotransferases, and liver volumes in individuals with CESD receiving recombinant enzyme (4–6). Long-term efficacy studies and the effect of ERT in individuals who failed liver or bone marrow transplant have not been done.
