Homozygous Familial Hypercholesterolemia

Definition

Homozygous familial hypercholesterolemia (HoFH) is a rare, inherited genetic disorder characterized by extremely high levels of low-density lipoprotein (LDL) cholesterol in the blood from birth. This condition leads to the early development of severe atherosclerosis and increased risk of cardiovascular disease.

5 Must Know Facts For Your Next Test

1. Individuals with HoFH have two faulty copies of the gene responsible for the LDL receptor, leading to severely impaired LDL cholesterol clearance from the bloodstream.
2. HoFH is a rare condition, affecting approximately 1 in 300,000 people worldwide, and is associated with a high risk of premature cardiovascular disease and death.
3. Patients with HoFH typically have LDL cholesterol levels exceeding 500 mg/dL, which is significantly higher than the normal range of 100-129 mg/dL.
4. Early diagnosis and aggressive treatment, including the use of cholesterol absorption inhibitors, are crucial in managing HoFH and reducing the risk of cardiovascular complications.
5. Genetic testing is essential for the diagnosis of HoFH, as it can help identify the specific genetic mutations responsible for the condition and guide appropriate treatment strategies.

Review Questions

• Explain the role of the LDL receptor in the development of homozygous familial hypercholesterolemia.
  • In homozygous familial hypercholesterolemia (HoFH), individuals have two faulty copies of the gene responsible for the LDL receptor, a protein that binds to and removes LDL cholesterol from the bloodstream. This genetic defect leads to severely impaired LDL cholesterol clearance, resulting in extremely high levels of LDL cholesterol in the blood from birth. The inability to effectively remove LDL cholesterol is the primary driver of the early development of severe atherosclerosis and increased cardiovascular disease risk in individuals with HoFH.
• Describe the clinical significance of the extremely high LDL cholesterol levels seen in patients with homozygous familial hypercholesterolemia.
  • Patients with homozygous familial hypercholesterolemia (HoFH) typically have LDL cholesterol levels exceeding 500 mg/dL, which is significantly higher than the normal range of 100-129 mg/dL. This profound elevation in LDL cholesterol leads to the early development of severe atherosclerosis, placing individuals with HoFH at a high risk of premature cardiovascular disease and events, such as heart attacks and strokes. The clinical significance of this condition is the need for aggressive treatment and management strategies, including the use of cholesterol absorption inhibitors, to mitigate the increased cardiovascular risk and improve patient outcomes.
• Analyze the role of genetic testing in the diagnosis and management of homozygous familial hypercholesterolemia.
  • Genetic testing is essential for the diagnosis of homozygous familial hypercholesterolemia (HoFH) because it can help identify the specific genetic mutations responsible for the condition. Identifying the underlying genetic defects, particularly in the genes coding for the LDL receptor, is crucial for guiding appropriate treatment strategies. With the knowledge of the specific genetic mutations, healthcare providers can tailor the management of HoFH, including the selection of the most effective cholesterol-lowering medications and the potential for early intervention, such as the use of cholesterol absorption inhibitors. Furthermore, genetic testing allows for the identification of at-risk family members, enabling early diagnosis and proactive management to prevent the development of severe cardiovascular complications associated with this rare, but life-threatening, genetic disorder.

Related terms

Familial Hypercholesterolemia: Familial hypercholesterolemia (FH) is an inherited disorder that causes high levels of LDL cholesterol, leading to an increased risk of heart disease. It can be inherited in either a homozygous or heterozygous form.

LDL Receptor: The LDL receptor is a protein on the surface of cells that binds to and removes LDL cholesterol from the bloodstream. Mutations in the gene that codes for the LDL receptor can lead to familial hypercholesterolemia.

Atherosclerosis: Atherosclerosis is the buildup of plaque (made up of cholesterol, fat, calcium, and other substances) in the arteries, which can restrict blood flow and increase the risk of heart attack and stroke.