Published online Jul 6, 2022. doi: 10.12998/wjcc.v10.i19.6728
Peer-review started: February 12, 2022
First decision: March 25, 2022
Revised: April 7, 2022
Accepted: April 30, 2022
Article in press: April 30 2022
Published online: July 6, 2022
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.
Core Tip: We report a male Chinese patient diagnosed with Familial hypercholesterolemia with a heterozygous mutation, 1448G>A (W483X), of the low-density lipoprotein receptor (LDLR). By reviewing the literature, we speculate that the mutation may affect LDLR metabolism or structure and may lead to that responded modestly after treatment with Proprotein convertase subtilisin/kexin type 9 inhibitor.