Yang Liu, Xiao Yan-Yan, Shao Liang, Ouyang Chang-Sheng, Hu Yao, Li Bin, Lei Li-Feng, Wang Hong
Department of Cardiology, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang 330006, Jiangxi Province, China.
Postgraduate School of Jiangxi University of Traditional Chinese Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang 330008, Jiangxi Province, China.
World J Clin Cases. 2022 Jul 6;10(19):6728-6735. doi: 10.12998/wjcc.v10.i19.6728.
Familial hypercholesterolemia (FH) is an autosomal dominant disorder that is characterized by severely increased low-density lipoprotein (LDL) cholesterol levels. At the same time, elevated LDL levels accelerated the development of coronary heart disease. Several classes of drugs are currently in use to treat FH. Proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) is novel one of these.
This manuscript reports a case of FH that responded modestly after treatment with PCSK9i and statin drugs. Of even more concern is that the patient frequently admitted to the hospital during a 12-year follow-up period. Subsequently, we identified a heterozygous mutation, 1448G>A (W483X) of the LDL receptor (LDLR) in this patient. The serum levels of PCSK9 (proprotein convertase subtilisin/kexin type 9) in the patient was 71.30 ± 26.66 ng/mL, which is close the average level reported in the literature. This LDLR mutation affects LDLR metabolism or structure, which may make it unsuitable for use of PCSK9i.
Our outcome demonstrates that LDLR-W483X represents a partial loss-of-function LDLR and may contribute to PCSK9i ineffective. In the meanwhile, additional measures are therefore required (particularly with gene sequencing or change the treatment plan) must be initiated as early as possible. Genetic testing for clinically challenging cases who do not respond to PCSK9i therapy is very helpful.
家族性高胆固醇血症（FH）是一种常染色体显性疾病，其特征是低密度脂蛋白（LDL）胆固醇水平严重升高。同时，升高的LDL水平加速了冠心病的发展。目前有几类药物用于治疗FH。前蛋白转化酶枯草溶菌素/kexin 9型抑制剂（PCSK9i）是其中的新型药物。
本手稿报告了一例FH患者，在用PCSK9i和他汀类药物治疗后反应一般。更令人担忧的是，该患者在12年的随访期内频繁住院。随后，我们在该患者中鉴定出低密度脂蛋白受体（LDLR）的杂合突变1448G>A（W483X）。该患者的PCSK9（前蛋白转化酶枯草溶菌素/kexin 9型）血清水平为71.30±26.66 ng/mL，接近文献报道的平均水平。这种LDLR突变影响LDLR的代谢或结构，这可能使其不适用于PCSK9i。
我们的结果表明，LDLR-W483X代表功能部分丧失的LDLR，可能导致PCSK9i无效。同时，因此需要尽早采取额外措施（特别是进行基因测序或改变治疗方案）。对PCSK9i治疗无反应的临床疑难病例进行基因检测非常有帮助。
