- 著者
- Masayuki Kuroda Hideaki Bujo Koutaro Yokote Takeyoshi Murano Takashi Yamaguchi Masatsune Ogura Katsunori Ikewaki Masahiro Koseki Yasuo Takeuchi Atsuko Nakatsuka Mika Hori Kota Matsuki Takashi Miida Shinji Yokoyama Jun Wada Mariko Harada-Shiba on behalf of the Committee on Primary Dyslipidemia under the Research Program on Rare and Intractable Disease of the Ministry of Health Labour and Welfare of Japan
- 出版者
- Japan Atherosclerosis Society
- 雑誌
- Journal of Atherosclerosis and Thrombosis (ISSN:13403478)
- 巻号頁・発行日
- pp.RV17051, (Released:2021-04-18)
- 参考文献数
- 68
- 被引用文献数
- 6
Lecithin cholesterol acyltransferase (LCAT) is a lipid-modification enzyme that catalyzes the transfer of the acyl chain from the second position of lecithin to the hydroxyl group of cholesterol (FC) on plasma lipoproteins to form cholesteryl acylester and lysolecithin. Familial LCAT deficiency is an intractable autosomal recessive disorder caused by inherited dysfunction of the LCAT enzyme. The disease appears in two different phenotypes depending on the position of the gene mutation: familial LCAT deficiency (FLD, OMIM 245900) that lacks esterification activity on both HDL and ApoB-containing lipoproteins, and fish-eye disease (FED, OMIM 136120) that lacks activity only on HDL. Impaired metabolism of cholesterol and phospholipids due to LCAT dysfunction results in abnormal concentrations, composition and morphology of plasma lipoproteins and further causes ectopic lipid accumulation and/or abnormal lipid composition in certain tissues/cells, and serious dysfunction and complications in certain organs. Marked reduction of plasma HDL-cholesterol (HDL-C) and corneal opacity are common clinical manifestations of FLD and FED. FLD is also accompanied by anemia, proteinuria and progressive renal failure that eventually requires hemodialysis. Replacement therapy with the LCAT enzyme should prevent progression of serious complications, particularly renal dysfunction and corneal opacity. A clinical research project aiming at gene/cell therapy is currently underway.