Advances in the Diagnosis and Management of Rare Disorders - Episode 7

Diagnosing Familial hypercholesterlemia and Other Cholesterol Disorders

Turning its attention to cholesterol disorders, the panel discusses hypercholesterolemia, which moderator Abhimanyu Garg, MD, describes as having a “one in a million prevalence in most of the western population,” as well as familial chylomicronemia, which he says affects “one in a million patients with lipoprotein lipase deficiencies.”

Garg notes that these conditions can cause other more harmful complications in patients, including premature coronary heart disease, stroke, and circulation issues. The moderator continues the discussion by saying that diagnosis of these conditions can be difficult for a variety of reasons.

“The diagnostic test to start with it is a lipid profile, but then I think it has to go forward with genetic testing to confirm the diagnosis,” he says. “Well, that’s where we are right now lagging because there are not many laboratories which can provide genetic testing for these disorders.”

Saying there is “some effort being made,” Garg said points to the development of screening for the LDL receptor gene, apolipoprotein gene, and PCSK9 gene, “which in extremely rare mutations cause high cholesterol.”

Panelist Vanessa Rangel Miller, MS, CGC, MBA, says the genetic aspect of diagnosis is especially important with these conditions.

“Making the diagnosis in the proband, in the first person in the family is very important, not only for their health to minimize any health effects from the diseases where we can, but also to evaluate and screen the health for the first degree family members which can be brothers, sisters. It could be parents. It could be children. And so making that first diagnosis and then having the genetic counseling to communicate to those first degree relatives what their health effect and risk could be, what steps they can take to either determine the diagnosis should they wish or to prevent manifestations and do screening.”

Susan Winter, MD, FAAP, FFACMG, says the “founder effect,” is important for doctors to keep in mind when treating patients with these conditions.

“One person, many generations before developed the mutation. Every 100,000 genes you copy, you make a mistake. So about one in every 4 sperm have a new genetic mutation in them and eggs. Once it’s founded and the community stays and inbreeds, you will get a lot of recessive disorders.”