Familial hypercholesterolemia (FH) is an inherited disorder of lipoprotein metabolism, transmitted in an autosomal dominant manner and clinically characterized by elevated levels of total cholesterol (TC) and low-density lipoprotein (LDL) cholesterol, the presence of tendon xanthomas, and premature atherosclerosis.The genetic basis of FH is a large array of point mutations and large gene rearrangements in the LDL receptor (LDLR) gene, resulting in defective functional receptors for LDL on the cell surface, which are unable to clear plasma LDL and result in increased plasma LDL levels. Similarly, point mutations in the gene coding for apolipoprotein B (APOB) also reduce LDL clearance, resulting in the disorder familial defective apolipoprotein B, which is clinically indistinguishable from FH. In 2003, a third FH locus located on chromosome 1, encoding proprotein convertase subtilisin/kexin 9 (PCSK9) was identified. The phenotypes caused by mutations in LDLR, APOB, or PCSK9 are clinically indistinguishable and all characterized by elevated levels of plasma LDL cholesterol and premature coronary artery disease.

The homozygous form of familial hypercholesterolemia (HoFH) with autosomal dominant transmission, in which case both alleles of either LDLR, APOB, or PCSK9 gene are defective, is a rare genetic disorder with prevalence estimated to be one per million population. Patients with HoFH have an extremely rapid accumulation of atherosclerosis with most experiencing xanthomas and severe vascular disease by adolescence or early adulthood despite interventions, including LDL apheresis, which led to the recent Food and Drug Administration approval of 2 novel therapies, lomitapide and mipomersen, specifically for HoFH. Heterozygous familial hypercholesterolemia (HeFH), in which only one allele of LDLR, APOB or PCSK9 gene is defective, has a prevalence of approximately one in 500 individuals, making it one of the most common inherited disorders. Reduction of elevated cholesterol levels in FH individuals can result in a significant reduction of cardiovascular mortality and morbidity, as a large number of landmark clinical trials with cholesterol synthesis inhibitors have clearly demonstrated. However, less than 10% of patients with HeFH are diagnosed and less than 25% are treated with LDL-lowering medications.

Large scale genetic screening for active FH cases finding has been performed in the Netherlands, Spain, Norway and Wales. However, the FH population and prevalence in Taiwan have never been formally studied. Patients are usually not under appropriate treatment owing to lack of standardized diagnostic tool and treatment strategy for FH. Moreover, with the emerging of new classes of LLTs, including microsomal triglyceride transfer protein (MTP) inhibitor, antisense oligonucleotide inhibitor, and PCSK9 inhibitors, even homozygous FH patients now have better chance to be treated to reach recommended treatment goals. Therefore, A National FH registry is needed to collect contemporary data on diagnosis, treatment and outcomes with long- term goals of improving diagnosis, management, and reduction of unnecessary cardiovascular events in FH population in Taiwan.