Understanding Homozygous Familial Hypercholesterolemia

Read this article in Spanish: Comprender la hipercolesterolemia familiar homocigótica (PDF)

Although only 1 in 300,000 people have homozygous familial hypercholesterolemia or HoFH, the effects of this genetic mutation are devastating without a diagnosis and treatment, said New York City cardiologist Dr. Eugenia Gianos.

The more common familial hypercholesterolemia mutation — heterozygous familial hypercholesterolemia or HeFH affects 1 in about 200 people (or nearly the same number as type 1 diabetes). HeFH happens when one parent passes on the mutated gene. When both parents have FH and pass the genes to a child, the child may have HoFH. The mutation reduces the ability of cells to remove LDL (bad) cholesterol from the bloodstream, increasing the risk of cardiovascular disease in childhood.

“I would say it’s almost a double hit,” said Dr. Gianos, who treats adult patients for advanced heart issues, including some who have HoFH, because their cholesterol was never controlled.
HoFH symptoms usually show up early in life with very high LDL cholesterol (greater than 400 mg/dl). Sadly, even young children with the mutation can have heart disease and heart attacks, Dr. Gianos said.

“Imagine having a child have a heart attack at age 7,” she said. “It’s astounding.”

Knowing your family history of heart disease is important. Sometimes a child's diagnosis of HoFH helps the parents get diagnosed and start "cascade screening" (PDF) | Spanish (PDF) for the entire family; the adults may not have been aware of their own mutation. If a parent does know they have the mutation, which is a familial condition, the child’s pediatrician should order testing starting at age 2, Dr. Gianos said.

“We need to recognize all these patients out there early enough,” she said. “As clinicians, we have to ask the right questions of the family.”

Physical symptoms of HoFH include yellowish miscoloring in the skin, which are cholesterol deposits, under the eyes, around the knuckles and around the Achilles tendons. The outer edge of the eye’s cornea may show a white, grey or yellow ring, and the patient may experience thickening in the Achilles tendons, hands or elbows.

While a healthy diet and lifestyle may help people with HoFH, food choices alone cannot solve everything, Dr. Gianos said.

“Patients are frustrated when they can’t fix it with diet,” she said. “It’s like me saying I’m going to work very hard to change my eye color. Well, you can’t. It’s genetic.”

But even though HoFH may cause severe heart disease, early diagnosis and treatment can be successful, Dr. Gianos said. Effective treatments include statins, non-statins and injectable medications, which in combination can make a big difference.

Another treatment available in some hospitals is a procedure called lipoprotein apheresis, where two IVs or ports help filter the cholesterol out of the blood and return the remainder of the blood to the body. This process also thins the blood and reduces inflammatory markers and clotting factors. Talk to your health care professional to see if this treatment is available and right for you.

“We all need to recognize it early. We need to direct patients to the right specialists to get their condition controlled,” she said. “With the right treatment, individuals can have normal, healthy lives.”