FH is a lipoprotein disorder resulting from defects in the hepatic uptake and degradation of LDL via the LDL-receptor pathway, commonly caused by a loss-of-function mutation in the LDL-receptor gene (LDLR) or by a mutation in the gene encoding apolipoprotein B (APOB). Causative mutations for FH can also lie within several secondary genes such as PCSK9, ARH, APOE, and LIPA. Affected individuals are characterized by elevations of LDL-Cholesterol > 95th percentile for age and gender and may show clinical manifestations (xanthomas, xanthelasmas and premature arcus corneus) although these manifestations are seen less frequently with early diagnosis and treatment. Untreated, FH will lead to premature atherosclerotic cardiovascular disease, primarily coronary artery disease, so early detection of affected individuals is a cornerstone of cardiovascular prevention. There are at least three accepted definitions for FH: the Simon-Broome criteria, the MedPed criteria, and the FH Dutch Lipid Clinic Criteria.
In Canada, there is no “gold standard” for the diagnosis of FH. Most of the FH patients are diagnosed on clinical and biochemical features:
1) very high LDL-C (typically > 5 mmol/L);
2) personal history of early cardiovascular disease;
3) typical physical findings (stigmata), xanthelasmas, arcus corneus, tendon xanthomas;
4) family history of early cardiovascular disease or of marked hyperlipidemia, often requiring treatment.
The Canadian Cardiovascular Society position statement on FH suggest that until standardized diagnosis criteria for FH are available in Canada, the diagnosis of FH should rely on the Simon Broome or Dutch Lipid Clinic criteria. A standardized diagnostic is under discussion and should be available in the upcoming years, with the help from the FH Canada registry data for its validation, and will greatly facilitate diagnosis of FH in the primary care setting. Please note that molecular testing for FH is rarely performed in Canada, due to lack of availability, non-standardization of methods and expense. The FH Canada registry initiative will help to make DNA testing more available, at least in cases of diagnostic uncertainty, family screening and in cases where therapeutic managements will be determined by the results of such testing.