A Registration Study for Familial Hypercholesterolemia in Taiwan
A Registration Study for Familial Hypercholesterolemia in Taiwan
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 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.

 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.
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.
Inclusion Criteria:

 -  Taiwan FH Diagnostic Criteria was revised from Dutch Lipid Clinic Network (DLCN)
 Criteria with consensus of experts in cardiology, genetic, and metabolism specialty,
 and published by Taiwan Society of Lipids & Atherosclerosis in 2014.

 Exclusion Criteria:

 -  The main exclusion criteria will be secondary causes of hyperlipidemia other than FH
 (i.e. untreated hypothyroidism, nephrotic syndrome), hemodynamically significant
 valvular or congenital heart disease, life-threatening malignancy, treatment with
 immunosuppressive agents, or any condition or situation which, in the opinion of the
 investigator, might be not suitable for this registration.