Why Early Detection is Key to Improving HoFH Outcomes, with Samuel Gidding, MD

Samuel Gidding, MD

Credit: Homework for Health

Homozygous familial hypercholesterolemia (HoFH), an ultra-rare inherited condition that causes life-threatening levels of low-density lipoprotein (LDL) cholesterol from birth. In an interview with The Educated Patient, Samuel Gidding, MD, discusses a recently published study that proposed a set of measures to reduce the burden of HoFH and advocated for universal newborn screening for the condition in the United States (US).

In addition to being the lead investigator of the paper, Gidding currently serves on the World Heart Federation’s Science Committee and has dedicated his career to studying pediatric preventive cardiology.

In your opinion, why is there an urgent need to increase awareness and screening for HoFH in the medical community?

Samuel Gidding, MD: There are two main reasons. First, the longer you delay diagnosis, the worse the patient outcomes. This condition leads to lifelong exposure to extremely high cholesterol, and any delay is harmful to the patient. Second, unlike 10 or even five years ago, we now have a range of new treatments available.

However, because of delayed diagnoses, we lack data on how effective these treatments could be in very young patients. Without identifying people early, we can't start treatment soon enough or gather the necessary safety data to confirm these new medications are as effective as we hope. So, early identification is crucial not only for the individuals diagnosed but also for the future of the entire HoFH community.

What are some of the long-term consequences of delayed diagnosis?

SG: The cardiovascular consequences would simply occur much earlier in life—heart attacks, aortic valve disease, for instance. We're not yet sure how well we can prevent aortic valve complications in individuals with HoFH, but for heart attacks, the data are clear: the lower you keep cholesterol levels, the longer you can delay these events.

How would universal newborn screening change the landscape of early diagnosis and treatment in the US?

SG: It would be transformative. Right now, the typical age of diagnosis is over five years. Occasionally, some children are diagnosed between ages two and five, but these tend to be very severe cases with physical signs of cholesterol deposits on the skin, eyes or tendons. By that point, they already have significant cholesterol buildup. Universal newborn screening would change that entirely.

What are the current barriers, both policy- and research-related, to implementing widespread screening programs, and how can these gaps be addressed?

SG: There are many rules and regulations around newborn screening, which is appropriate because the condition being screened for needs to be actionable and benefit from early diagnosis. Conditions like hypothyroidism and phenylketonuria are classic examples where early diagnosis prevents significant cognitive impairment, and effective treatments are available. I believe a similar case can be made for FH, and researchers are currently working to validate the use of cholesterol levels in the same dried blood spots used for other screenings.

Although there are issues with genetic testing, as it becomes more accessible, many are advocating for this. In the United Kingdom, for example, they’re considering adding FH genetic testing to a potential newborn screening panel for actionable genetic conditions. There’s worldwide momentum, with newborn screening programs already operating in Germany and the Czech Republic. As we gather more data from these programs, it will help inform decision-making in the US.

Is there anything else you’d like our audience to know?

SG: Screening not only helps identify individuals with HoFH or homozygous FH but also detects severe forms of heterozygous FH, which can also benefit from early treatment and recognition. While you might not start treatment at birth for heterozygous FH, in severe cases, early treatment in childhood could make a significant difference.

This transcript was edited for clarity.