Medical experts illustrate an array of characteristics presented in patients with HoFH.
Erin Michos, MD, MHS: In homozygous FH [familial hypercholesterolemia], the LDL [low-density lipoprotein] cholesterol—the bad cholesterol—is between 400 and 100 mg/dL, which is over 4 times the normal level. That translates to an onset of cardiovascular disease in childhood. Children can suffer a cardiac event or myocardial infarction, and cases have been reported as young as 4 years of age. Untreated patients with homozygous FH have a life expectancy of less than 30 years with the onset of atherosclerotic cardiovascular disease even before the age of 20, as teenagers. This is why it’s so important that the earliest initiation of lipid-lowering therapy is required to prevent premature cardiovascular disease, given the risk of mortality before the age of 30 if not treated.
Homozygous FH is an autosomal dominant genetic disorder. That means men and women are affected equally. Although FH affects all races and ethnicities, certain subpopulations experience higher frequency, which thought to have a founder effect in populations such as French Canadians, Ashkenazi Jews, Christian Lebanese, Finnish, and South African Afrikaners. But everybody—all races and ethnicities—can be affected, and there’s an underdiagnosis of FH in individuals from non-European backgrounds. There are disparities by race and ethnicity.
Atherosclerotic cardiovascular disease is already present as a subclinical disease in asymptomatic children. Early signs can be coronary occlusions or erratic valve abnormalities, mainly aortic stenosis. The cutaneous signs can be tendons and xanthomas on the corneal arcus, which are typical features found on the physical exam. Xanthelasmas and xanthomas are cholesterol deposits that are found on the skin around the eyes and on the tendons. The corneal arcus is this half circle of gray, white, or yellow cholesterol deposits on the outer edge of the cornea. The findings and the urgency about treating this is why the American Academy of Pediatrics recommends lipid screening in children as young as age 2 if they have a family history of early onset cardiovascular disease in a parent—before age 55 in a man and 65 in a woman.
Eliot Brinton, MD: One factor about homozygous FH is that it’s almost entirely genetic. There’s very little environmental impact. Obesity is not an issue. Diet has minimal impact, although we advocate for a good diet. Exercise is not really a factor. There are many things that play a role in general hypercholesterolemia and heterozygous FH. These factors do play a role.
One interesting fact about FH in general and homozygous FH in particular is that it’s not related to diabetes. Granted, diabetes will increase the risk of atherosclerosis in anyone, but there’s a little suppression in the risk of diabetes with even heterozygous FH, especially with homozygous FH. It’s a little unusual to see somebody with homozygous FH who has type 2 diabetes. As everyone knows, we’re seeing more type 2 diabetes in children and adolescents. It’s not that that’s unusual, but the children and adolescents we’re diagnosing and treating for homozygous rarely if ever have diabetes, and they don’t tend to be fat. It’s an adverse situation with what we tend to see with cholesterol and other lipid disorders in the general sense.
Seth Baum, MD: The presentation of homozygous and heterozygous FH is interesting and disturbing. One would think that homozygous FH, which is the most severe form of FH—with the highest LDL levels and the greatest risk of cardiovascular disease—would be identified very early in life, prior to any cardiovascular event occurring. Unfortunately, that’s not the case. If we look at the presentation in children from the Cascade-FH Registry, which was a 40-site registry done through the [Family Heart] Foundation, we see that the mean age of diagnosis was 9 years; in adults, it was 30 years. Individuals who have LDLs of 500, 600, 700 mg/dL or above, unfortunately, often present with an event. In adults in particular, they present with a significant cardiovascular event, a heart attack, a stroke, and angina. Children sometimes present that way as well. More typically, somebody identifies the severely elevated LDL levels, although nearly half the children at the time of diagnosis already have established ASCVD [atherosclerotic cardiovascular disease].
Transcript edited for clarity.