It is Time to Screen for Homozygous Familial Hypercholesterolemia in the United States

Area of Science:

• Genetics and Cardiovascular Disease
• Metabolic Disorders
• Public Health Policy

Background:

• Homozygous familial hypercholesterolemia (HoFH) is an ultra-rare inherited disorder affecting ~1 in 300,000 individuals.
• Characterized by extremely high LDL cholesterol from birth, HoFH leads to severe premature cardiovascular morbidity and mortality if untreated.
• HoFH is significantly underdiagnosed and undertreated in the US, despite existing pediatric screening guidelines.

Purpose of the Study:

• To highlight the urgent need for improved diagnosis and treatment of HoFH in the US.
• To advocate for policy implementation ensuring timely HoFH detection, especially in infants.
• To propose actionable measures for states to reduce the HoFH burden and address policy gaps for universal newborn screening.

Main Methods:

• Review of current HoFH diagnosis and treatment landscape in the US.
• Analysis of European pilot studies on newborn screening for HoFH.
• Development of policy recommendations for state-level implementation.

Main Results:

• HoFH diagnosis is often delayed, occurring after major cardiovascular events.
• Current pediatric screening guidelines (ages 9-11) miss early-onset HoFH.
• European recommendations suggest broadening guidelines to include newborn screening for HoFH.

Conclusions:

• Timely diagnosis and treatment are critical to avert premature cardiovascular disease in HoFH patients.
• Universal newborn screening for HoFH is a necessary policy to address underdiagnosis.
• Further research and policy development are needed to implement effective newborn screening strategies for HoFH in the US.