Tamaki Atsuko, Kuroda Masayuki, Yonaha Ken, Ishiki Yohei, Uehara Moriyuki, Nakayama Yoshiro, Honma Ken-Ichiro, Chinen Rei, Uema Tsugumi, Okamoto Shiki, Miyoshi Junko, Kirinashizawa Mika, Sato Kazuki, Aohara Tsutomu, Yamamoto Misato, Maezawa Yoshiro, Yokote Koutaro, Masuzaki Hiroaki
Division of Endocrinology, Diabetes and Metabolism, Hematology and Rheumatology, Second Department of Internal Medicine, Graduate School of Medicine, University of the Ryukyus.
Center for Advanced Medicine, Chiba University Hospital, Chiba University.
J Atheroscler Thromb. 2025 May 1;32(5):649-659. doi: 10.5551/jat.65298. Epub 2024 Dec 10.
A 59-year-old Japanese woman was referred for an extremely low level of circulating high-density lipoprotein cholesterol (HDL-C). The serum HDL-C level had long been within the normal range but suddenly decreased asymptomatically to 7 mg/dL. She had no typical symptoms associated with familial lecithin, cholesterol acyltransferase deficiency (FLD), including proteinuria, anemia, and corneal opacity. The circulating level of ApoA-1 was also markedly decreased at 48 mg/dL, and the proportion of esterified cholesterol to free cholesterol was irregularly low at 26%. Whole-genome sequencing revealed no apparent pathological mutations in the LCAT gene. Notably, anti-LCAT antibodies were detected in the serum at 146±1.7 ng/mL, resulting in her being diagnosed with acquired LCAT insufficiency (ALCATI) caused by anti-LCAT antibodies. Five years after her HDL-C levels spontaneously decreased, they increased without any identifiable cause. To our knowledge, only six cases of ALCATI caused by anti-LCAT antibodies have been reported to date. In contrast to the present case, previously reported cases of ALCATI manifested proteinuria that improved with steroid therapy. The unique clinical course in the present case highlights the heterogeneity of ALCATI, warranting further research to clarify the molecular pathophysiology of FLD and ALCATI.
一名59岁的日本女性因循环中高密度脂蛋白胆固醇（HDL-C）水平极低而前来就诊。血清HDL-C水平长期处于正常范围，但突然无症状地降至7mg/dL。她没有与家族性卵磷脂胆固醇酰基转移酶缺乏症（FLD）相关的典型症状，如蛋白尿、贫血和角膜混浊。载脂蛋白A-1的循环水平也显著降低，为48mg/dL，酯化胆固醇与游离胆固醇的比例异常低，为26%。全基因组测序未发现LCAT基因有明显的病理性突变。值得注意的是，血清中检测到抗LCAT抗体，浓度为146±1.7ng/mL，导致她被诊断为由抗LCAT抗体引起的获得性LCAT缺乏症（ALCATI）。在她的HDL-C水平自发下降五年后，又无明显原因地升高。据我们所知，迄今为止仅报道了6例由抗LCAT抗体引起的ALCATI病例。与本病例不同的是，先前报道的ALCATI病例表现为蛋白尿，经类固醇治疗后有所改善。本病例独特的临床过程突出了ALCATI的异质性，需要进一步研究以阐明FLD和ALCATI的分子病理生理学。
