Homozygous familial hypercholesterolemia (HoFH) is an orphan disease characterized
by extremely high levels of plasma levels of LDL-C. Affected patients develop clinical
atherosclerotic cardiovascular disease (ASCVD) in youth and survival > 30 years of
age was unusual until the advent of medications (statins) and extracorporeal LDL filtration
(apheresis) techniques. HoFH is an autosomal co-dominant condition defined as an LDL-C
> 13 mmol/L in adults without treatment and homozygous or compound heterozygous mutations
of the LDLR gene. HoFH has a genetic probability of ∼1/386,000 and the rare diseases
inventory Orphanet estimates its worldwide prevalence at 1/1,000,000 individuals.
Canada is known to have several regions with a founder effect for HoFH and we identified
79 cases across the country. Data from other countries show a median survival of HoFH
patients at <40 years of age. Clinical outcomes in HoFH patients, especially ASCVD
events (fatal and non-fatal myocardial infarctions, strokes and peripheral vascular
disease) and severe calcific aortic stenosis, are difficult to capture, in part because
of the rarity of the disorder and the lack of registry focusing on this disease. The
objective of our project is to obtain a comprehensive registry of HoFH in Canada,
estimate the cost to society caused by HoFH burden of disease in Canada, and implement
changes to advocate access to specialized care for these patients.
METHODS AND RESULTS
Here, we present preliminary data (Table 1) on our Canadian HoFH registry, including
medical history, levels of LDL-C, treatments and outcomes of 21 HoFH patients.
We plan to use this data at provincial and national levels, in help with the Canadian
Organization for Rare Diseases (CORD) and the Réseau Québecois des maladies orphelines
(RQMO), to provide HoFH patients access to care, including PCSK9 inhibitors, orphan
drugs such as lomitapide and evinacumab, and treatment techniques such as extracorporeal
LDL filtration (apheresis). This work will provide important new health-related knowledge
about the determinants of ASCVD risk and phenotypic manifestations of HoFH in Canada
and examine the quality of life and burden to the healthcare system.