An Introduction to Homozygous Familial Hypercholesterolemia (HoFH)
Familial hypercholesterolemia is a kind of genetic disorder that is caused by a defect of chromosome 19. The disorder can be passed genetically to a child from one or both parents. There are two distinct types of familial hypercholesterolemia, heterozygous FH and homozygous FH. Heterozygous FH occurs when a patient has one abnormal copy of the LDL receptor gene, passed from one parent; homozygous FH occurs when there are two abnormal copies of the LDL receptor gene, passed from both parents.
Homozygous FH (HoFH) is much less prevalent in the general population than heterozygous FH. Heterozygous FH is estimated to occur in one of every 500 people living in the developed world. Homozygous FH occurs in one of every million infants born.
The symptoms of HoFH include high cholesterol in the blood. Specifically, a person’s body is less able to remove low-density lipoprotein, LDL, from the blood. LDL is commonly referred to as “bad” cholesterol, by contrast with high-density lipoprotein which is considered “good” cholesterol. High LDL cholesterol levels increase the risk of atherosclerosis — narrowing or “furring” of the arteries due to cholesterol build-up. In a patient with HoFH, artherosclerosis, and potential cardiovascular disease, can appear as symptoms during childhood. Noticeable physical symptoms of HoFH can include visible fatty deposits , known as xanthomas, on the ankles, knees, elbows or hands. These deposits can also appear in the eyelids, or around the eye’s cornea. Symptoms of coronary artery disease, such as pain in the chest, may also be present in young patients.
Diagnosis of HoFH typically involves an examination looking for xanthomas on the eye, hand, or lower extremities. A family medical history can determine whether there is a genetic risk of an individual having HoFH. If one or both parents have high LDL levels, or if there is a general family history of high cholesterol and early heart attacks, this can inform a HoFH diagnosis. Diagnostic blood tests look for high cholesterol levels, and high LDL levels in particular, together with normal triglyceride levels. Genetic testing, and a kind of cellular test called a fibroblast, can also be used in the diagnosis of HoFH.
The treatments commonly used for heterozygous FH — typically statins and other substances intended to decrease a patient’s cholesterol levels — do not generally work to treat HoFH. The rarity of HoFH means that treatment options are limited, and still in a state of development. A patient with HoFH can be treated by dialysis-like removal of LDL from their blood — this process is called LDL apheresis. In some cases, a liver transplant can be helpful in treating or managing HoFH. Lifestyle and dietary factors can further help manage HoFH and control cholesterol levels.
This article was contributed by Genpharm Services, a leading pharmaceutical firm who has recently partnered with Aegerion Pharmaceuticals to commercialize Juxtapid (Lomitapide), an Orphan drug from indicated for patients with Homozygous Familial Hypercholesterolemia (HoFH), in the Levant region. To find out more about Genpharm click here.
The World Orphan Drug Congress team is delighted to welcome Genpharm as a sponsor to the 2013 event, taking place in November! Find out more about this event here >