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

• Published in: Global heart 2024-05, Vol.19 (1), p.43-43
• Main Authors: Gidding, Samuel S, Ballantyne, Christie M, Cuchel, Marina, de Ferranti, Sarah, Hudgins, Lisa, Jamison, Allison, McGowan, Mary P, Peterson, Amy L, Steiner, Robert D, Uveges, Melissa K, Wang, Yunshu
• Format: Article
• Language: English
• Subjects: best screening practices; Child; Cholesterol, LDL - blood; Homozygote; homozygous familial hypercholesterolemia; Humans; Hyperlipoproteinemia Type II - diagnosis; Hyperlipoproteinemia Type II - epidemiology; Hyperlipoproteinemia Type II - genetics; Infant, Newborn; Mass Screening - methods; Neonatal Screening - methods; newborn screening; United States - epidemiology; universal
• ISSN: 2211-8179; 2211-8179
• DOI: 10.5334/gh.1316

Homozygous familial hypercholesterolemia (HoFH) is an ultra-rare inherited condition that affects approximately one in 300,000 people. The disorder is characterized by extremely high, life-threatening levels of low-density lipoprotein (LDL) cholesterol from birth, leading to significant premature cardiovascular morbidity and mortality, if left untreated. Homozygous familial hypercholesterolemia is severely underdiagnosed and undertreated in the United States (US), despite guidelines recommendations for universal pediatric lipid screening in children aged 9-11. Early diagnosis and adequate treatment are critical in averting premature cardiovascular disease in individuals affected by HoFH. Yet, an unacceptably high number of people living with HoFH remain undiagnosed, misdiagnosed, and/or receive a late diagnosis, often after a major cardiovascular event. The emergence of novel lipid-lowering therapies, along with the realization that diagnosis is too often delayed, have highlighted an urgency to implement policies that ensure timely detection of HoFH in the US. Evidence from around the world suggests that a combination of universal pediatric screening and cascade screening strategies constitutes an effective approach to identifying heterozygous familial hypercholesterolemia (HeFH). Nevertheless, HoFH and its complications manifest much earlier in life compared to HeFH. To date, little focus has been placed on the detection of HoFH in very young children and/or infants. The 2023 Updated European Atherosclerosis Society Consensus Statement on HoFH has recommended, for the first time, broadening pediatric guidelines to include lipid screening of newborn infants. Some unique aspects of HoFH need to be considered before implementing newborn screening. As such, insights from pilot studies conducted in Europe may provide some preliminary guidance. Our paper proposes a set of actionable measures that states can implement to reduce the burden of HoFH. It also outlines key research and policy gaps that need to be addressed in order to pave the way for universal newborn screening of HoFH in the US.