By Dr. Zahrul Ismadi MBBS DCH FRACP FHGSA
Familial Hypercholesterolemia (FH) is a genetic disorder characterized by high cholesterol levels, specifically very high levels of low-density lipoprotein cholesterol (LDL, or “bad cholesterol”) in the blood, which leads to premature cardiovascular disease.
Individuals with FH have a higher than normal amount of LDL due to a genetic change in one of the genes that control the way cholesterol is processed by the body. As a result, cholesterol accumulates and deposits on the walls of major blood vessels, including the arteries of the heart. Over time, this buildup, known as atherosclerosis, can lead to heart disease and stroke as early as the second decade of life.
Symptoms of Familial Hypercholesterolemia can vary among individuals. Some people may not show any symptoms until they experience a heart attack or stroke, while others may notice fatty skin deposits called xanthomas over parts of the hands, elbows, knees, ankles, and around the cornea of the eye.
FH is a treatable genetic disorder, and with aggressive management, the onset of early cardiovascular diseases can be delayed. Studies have consistently demonstrated that high levels of cholesterol have a cumulative effect over time; therefore, early detection is key. Unfortunately, FH remains underdiagnosed and undertreated in the Australian population. FH should be considered in individuals of all ages if there is a history of premature cardiovascular events (such as heart attack or stroke) in first-degree relatives, clinical features of FH such as fatty deposits around the eyes, tendons, or in the cornea, which can be quite subtle, especially in children. Screening for FH typically involves a blood test for a lipid profile, followed by genetic testing. It is recommended that children are screened from ages 2-5 years.
FH is inherited in an autosomal co-dominant manner. This means that a person will manifest the disorder even with a variation in only one copy of the gene, while the other copy is normal (heterozygous FH). Those with heterozygous FH will have a 50%, or 1 in 2, chance of passing the disorder to their offspring. If an individual inherited a genetic change in both copies of the gene (one from each parent), the disorder will be significantly more severe, including clinical symptoms developing in childhood (homozygous FH). All offspring of individuals with homozygous FH will develop heterozygous FH. FH affects both males and females similarly. The complex inheritance of FH is summarized in the pedigree below:
Therapeutic intervention for FH includes a combination of dietary intervention, lifestyle modification, and pharmacological therapy, all of which are complementary to each other. A comprehensive dietary assessment is mandatory to ensure appropriate fat restriction while maintaining essential fatty acids for normal body function. There is an increasing number of medications becoming available to treat FH. The main group of medication is called statins, which lower LDL cholesterol levels. Other treatments may include cholesterol absorption inhibitors and bile acid sequestrants. Novel therapies that alter the function and expression of PCSK9 and APOC3 are also becoming available for adult patients, with clinical trials in children underway. Lifestyle modifications, including a healthy diet, regular exercise, and avoidance of tobacco smoke, are also important in managing FH.
In summary, FH is an underdiagnosed but treatable disorder that requires a multidisciplinary team approach centered around affected individuals. Early diagnosis and treatment can help individuals with FH minimize the risk of premature macrovascular complications and live a healthy and productive life. Regular check-ups and follow-ups with your healthcare provider are key to managing this condition effectively. If you suspect you may have Familial Hypercholesterolemia, please consult with a healthcare provider for a thorough evaluation.
Dr. Zahrul Ismadi and Ms. Stephanie Gilroy provide evidence-based care for families with FH at Gems Medical Specialists. Please contact Gems Medical Specialists at 02 7228 4428 or reception@gemsmedic.com to arrange a consultation.
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