If your pediatric patient is overweight and has a family history of high cholesterol or heart disease, it may be worth screening for familial hypercholesterolemia (FH).

FH is an inherited disorder that affects the recycling of low-density lipoprotein (LDL) cholesterol, according to the American Heart Association (AHA). As a result, people with the disorder have high LDL cholesterol and are at a higher risk for heart disease.

People with one gene with a mutation for the LDL cholesterol receptor have heterozygous FH. The condition affects about 1 in 250-300 individuals. People who inherit the gene from both parents have homozygous FH, which is rarer, affecting an estimated 1 in 300,000 persons. It’s also more serious and can lead to heart attacks even in childhood, if not managed aggressively.

Although FH affects an estimated 1.3 million people in the US, only about 10% are aware they have it, according to the AHA. Children with FH are asymptomatic, and unfortunately, the first sign can be a heart attack, said Amy Peterson, MD, director of Pediatric Preventive Cardiology at the University of Wisconsin School of Medicine and Public Health in Madison, Wisconsin, and co-author of a recent study on identifying FH through newborn screening.

“If you can find heterozygous familial hypercholesterolemia at a younger age, there is really strong evidence that starting treatment for those children to lower their cholesterol prevents heart disease and prevents death from cardiac causes,” Peterson said. Diagnosis also can help point to the condition in parents, who may be unaware they have it, too, she said.

The vast majority of children with heterozygous FH can be treated effectively with lifestyle changes and statins, often at very low doses, Peterson said. Some patients will require multiple medications to lower LDL cholesterol.

Medical treatment can start as young as age 8, although lifestyle modifications can be started when the child is much younger, Peterson said.

How do you know when to screen? The biggest tip-off is family history of FH or cardiovascular disease in young people in the family, said Erin Adonnino, MD, general pediatrician with Wilmington Health in Wilmington, North Carolina.

Screening can be done in children as young as 2 with a fasting lipid panel, she said. If there’s no family history but other family members have high cholesterol, primary care physicians can follow the 2011 recommendations from the National Heart, Lung and Blood Institute to screen for high cholesterol at ages 9-11 and again at ages 17-21, she said.

Other signs of potential FH include yellowish fatty collections called xanthomas seen under the skin; around the eyes; or at the back of the hands, palms, or soles or a gray ring called a corneal arcus around the colored part of the eyes, said Melissa Chambers, DO, pediatric endocrinologist with Phoenix Children’s Hospital in Phoenix.

Seeing these signs should tip off clinicians that the patient should be referred for FH testing. It’s “one of the reasons that it’s so important for kids who are totally healthy to go get their annual checkups with their primary care physicians because they might pick that up before they ever had a blood test,” Chambers said.

In children without a known family history of high cholesterol or early heart disease, an LDL level of 190 mg/dL or higher suggests the possibility of at least a milder form of FH, she said. In children who do have a family history of high cholesterol and/or early heart disease, an LDL of 160 mg/dL or higher “is generally our threshold for further screening,” Chambers said.

Diagnostic criteria for the more severe form in both children and adults include treated LDL of 300 mg/dL or higher, untreated LDL of 500 mg/dL or higher, plus xanthomas seen before age 10, plus elevated LDL in both parents.

Patients with homozygous FH should be referred to a specialist, Peterson said. “But I feel very strongly that with the appropriate education, uncomplicated heterozygous FH can be managed by primary care pediatricians and family medicine [doctors]. They just need the education and the tools to be able to do it,” she said.

The main role for primary care physicians is in screening, diagnosis, and management of lifestyle interventions such as diet or weight loss.

“We like to work in a multidisciplinary team,” Adonnino said. One group to get involved is pediatric cardiology, because the patient is at higher risk for heart disease. Pediatric cardiologists can handle the medicine management, usually a statin or PCSK9 inhibitor. Primary care physicians also can call on lipid specialists, typically endocrinologists, she said. “It’s good to have them involved as well because kids with high cholesterol can have problems with obesity and diabetes.” Adonnino also sometimes brings in a genetic counselor to screen additional family members. A dietitian or nutritionist can help if the primary care physician doesn’t feel comfortable managing diet, she noted.

Through medication, the goal is to get LDL under 100 mg/dL, Chambers said. Ezetimibe or PCSK9 inhibitors can be added as needed. In cases of homozygous FH, specialists can turn to plasmapheresis to help remove excess cholesterol from the blood, she said.

Counseling families also is important for management.

“I make sure the family understands what’s going on in the body — this isn’t anyone’s fault, and, while eating healthy is important, this wasn’t caused by eating too much candy or junk food,” Chambers said. “I explain that there is a risk of early heart disease if cholesterol levels stay high and stress the importance of regular cholesterol checks.”

Adonnino emphasized the importance of preventing damage to the heart. “These children can live completely normal lives. It’s not going to stop them from doing anything that they want to do; it’s just something that we have to be thoughtful of, so that we’re protecting them.”

Also, remember there are plenty of other drivers of high cholesterol, Adonnino said. “To have the diagnosis of FH, you have to rule out the other causes — and there are a whole slew of them. You could have problems with your thyroid or liver or kidneys. Certain medications can cause you to have high cholesterol. Honestly, a lot of times what we’re seeing is more from obesity and eating high saturated fat.”

But if it is FH, “It’s a treatable thing. It doesn’t have to be terrifying, and resources are available to help primary care docs who want or need to manage it themselves,” Chambers said.

The nonprofit Family Heart Foundation published a summary of its 2024 summit to promote early identification of children living with FH, noting that despite screening recommendations, recent studies indicate that only 11% of youth ages 9-21 had documented lipid screening. The Foundation’s strategies include developing educational content for families and primary care pediatricians to improve universal lipid screening.

Peterson, Adoninno, and Chambers reported having no relevant financial disclosures.

Karen Blum is a freelance medical/science writer in the Baltimore area.