Understanding HoFH

Dr. Brunham is an Associate Professor in the Department of Medicine at the University of British Columbia, a Canada Research Chair in Precision Cardiovascular Disease Prevention, and the Medical Lead of the Healthy Heart Program Prevention Clinic at St. Paul’s Hospital.

_1.What is HoFH? How does it differ from heterozygous familial hypercholesterolemia (HeFH) and familial hypercholesterolemia (FH)?

 Homozygous familial hypercholesterolemia (HoFH) is a very rare and serious disorder of cholesterol metabolism that affects around 1 in 275,000 to 1 in 300,000 people in Canada. Children with HoFH have two DNA variants, or mutations – one inherited from their mother and one from their father.

Children with HoFH are born with extremely high levels of cholesterol in their blood. The earliest signs of the disease are often visible skin manifestations (xanthomas) caused by an accumulation of cholesterol in the skin. What’s beneath the surface is the cholesterol accumulating in the blood vessels of the heart, brain, and major heart valves, leading to early-onset heart disease. Without intervention, HoFH is uniformly lethal by age 30.

Heterozygous familial hypercholesterolemia (HeFH), or FH for short, is much more common (it affects about 1 in 300 people in Canada). Those affected have one mutated copy of this gene, which results in high levels of cholesterol and an increased risk of early-onset heart disease. HeFH is a serious medical condition that requires treatment, but, it’s nowhere near as severe as HoFH.

_2.Why is early diagnosis important for HoFH patients?

Early diagnosis is critical because of how severe the disease is. Without treatment, children with HoFH can have heart attacks by the age of 10 because of clogged heart vessels. If untreated, this will lead to progression of the disease and ultimately death.

Identifying patients with HoFH is essential so that treatment can be initiated, but the diagnosis isn’t always straightforward. While the skin manifestations can help diagnose children, HoFH often goes unrecognized because it’s such a rare disease and health care practitioners aren’t used to checking cholesterol levels in children. Any delay means a lost opportunity to lower cholesterol levels, which is essential for improving outcomes for patients.

“What’s beneath the surface is the cholesterol accumulating in the blood vessels of the heart, brain, and major heart valves, leading to early-onset heart disease. Without intervention, HoFH is uniformly lethal by age 30.”

_3.You’ve been diagnosed with HoFH. Now what?

Because it’s such a rare condition and the treatment is highly specialized, it’s essential that newly diagnosed patients get connected to a specialist who has expertise in the management of HoFH. That generally means being connected with a specialized centre for lipid management so they can get started on treatment as well as the other supports that are essential to these patients, including dietary counselling and lifestyle modifications.

_4.What kinds of challenges are associated with caring for and developing novel therapeutics for rare patient populations?

Children with HoFH require significant, lifelong treatment approaches, which place a high burden on caregivers. This includes attending appointments, maintaining medication regimens, and managing the consequences of their child being on a number of different medications.

For children and adults, treatment can require travel to specialized centres (of which there are only a handful in Canada), where they must undergo several hour-long sessions of blood cleaning, or apheresis. We have patients who live outside of major centres who have to travel in, sometimes by plane, to receive these treatments. Attending these sessions on a regular basis is very disruptive to a family’s lifestyle and there are significant social and emotional implications for both patients and caregivers.

Last but not least, there are challenges associated with the research and development of novel treatments. We must continue to encourage companies to make treatment accessible to, and affordable for, Canadians living with ultra-rare conditions like HoFH.

_5.Why is it a hopeful time for Canada’s HoFH community?

There are a couple of reasons to be optimistic. One is that we’re seeing increased recognition and engagement of the patient community. Having patients come together and advocate for themselves is an extremely beneficial and important aspect of raising awareness and ensuring that there’s appropriate and equitable access to diagnostics and therapies. 

At the same time, we’re seeing the development of some exciting new therapies for treating HoFH. There are a number of medications that have been developed specifically to treat this condition. This represents a major advance over what we previously had in terms of our ability to lower cholesterol levels for patients with genetic mutations. In some cases, it means that patients aren’t required to undergo invasive blood cleaning treatment sessions as frequently and some patients may no longer require them at all. These therapies are a real breakthrough and game-changer for patients, but there’s still work to be done to ensure that all patients in Canada have access to them once they’re approved.

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This initiative was supported by Ultragenyx. This page and the editorial themes covered were developed by Patient Voice.