Lipoprotein Disorders

A 12-year-old boy presents to the emergency department with chest pain after gym class. His parents note that he has been having increased episodes of difficulty catching his breath after exertion and has had previous episodes of chest pain on exertion. Upon physical exam yellow deposits are found on his heels and on his eyebrows. Based on clinical suspicion a LDL level is obtained and is found to be 480 mg/dL. He is referred to a geneticist for evaluation of deficiencies in LDL receptors and is prescribed a statin.

Hyperlipoproteinemia Overview

Type I hyperlipoproteinemia (hyperchylomicronemia)
- pathophysiology
  - deficiency in lipoprotein lipase or apoC-II
    - results in ↑↑↑↑ TGs, chylomicrons
- presentation
  - eruptive xanthomas
  - steatosis
  - abdominal pain post-fat ingestion
  - retinitis pigmentosa
Type II hyperlipoproteinemia
- pathophysiology
  - deficiency in LDL receptors
    - type IIa (familial hypercholesterolemia) results in ↑↑↑↑ LDL
      - >260 mg/dL
      - see Cholesterol topic
    - type IIb (familial combined hyperlipidemia) results in ↑↑↑↑ LDL, TGs, cholesterol
- presentation
  - deposition of cholesterol in normal tissue
    - xanthomas
    - xanthelasma
  - ↑↑ risk for coronary heart disease
Type III hyperlipoproteinemia (familial dysbetalipoproteinemia)
- pathophysiology
  - deficiency in apolipoprotein E
    - remember: III lacks E
    - results in ↑↑↑ in remnants (chylomicron/ IDL)
      - apolipoprotein normally clears remnants (empties)
- presentation
  - similar to type II hyperlipoproteinemia
  - ↑↑ risk for coronary heart disease
Type IV hyperlipoproteinemia (familial hypertriglyceridemia)
- pathophysiology
  - ↓ removal or ↑ production of VLDL
    - results in ↑↑↑ in VLDL
  - presentation
    - pancreatitis
Type V hyperlipoproteinemia
- type I + type IV
  - ↓ lipoprotein lipase + ↑ VLDL
  - remember: 1+4=5
Acquired hypercholesterolemia
- obstructive jaundice
- oral contraceptives
Acquired hypertriglyceridemia
- alcoholism
- renal failure
- diabetes mellitus
Treatment for hyperlipoproteinemias
- dietary modifications (type I)
- statins (type II – IV)
- niacin (type II, IV, V)
- fibrates (type IIa, IV, V)
bile acid sequestrants (type IIa)

Hypolipoproteinemia Overview

Abetalipoproteinemia
- AR
- pathophysiology
  - due to mutations in the microsomal triglyceride transfer protein (MTTP)
  - deficiency in apolipoprotein B-48 and B-100
    - remember: A (without) beta (B)
  - ↓ chylomicrons (B-48), VLDL/LDL (B-100)
- presentation
  - malabsorption of fat
    - can enter enterocytes but cannot exit because it cannot be packaged for release in lipoproteins
    - leads to histological appearance of fat droplets inside enterocytes
  - ↓ vitamin E absorption
  - ataxia
hemolytic anemia with acanthocytes

High Yield

Remember that type I, IIa, and IV are the most common types of hyperlipoproteinemia
I and IV present with pancreatitis, IIa presents with early symptoms of ACS
Treat all types other than I with statins, niacin, and fibrates

Symptoms

Lipoproteins are complex molecules made up of proteins and lipids (fats) that transport cholesterol and triglycerides through the bloodstream. Disorders that affect lipoproteins can lead to a range of symptoms and health problems. Here are some of the symptoms associated with lipoprotein disorders:

High cholesterol: Elevated levels of cholesterol in the blood, particularly low-density lipoprotein (LDL) cholesterol, can increase the risk of heart disease, stroke, and other cardiovascular problems. High cholesterol usually has no symptoms but can be detected through blood tests.
Xanthomas: These are yellowish, fatty deposits that can develop on the skin and tendons, particularly around the eyes, elbows, knees, and heels. Xanthomas are a sign of high cholesterol and can be a symptom of lipoprotein disorders.
Chest pain: Lipoprotein disorders that lead to atherosclerosis (hardening and narrowing of the arteries) can cause chest pain, angina, or heart attacks.
Peripheral artery disease (PAD): Lipoprotein disorders that cause atherosclerosis can also affect the blood vessels in the legs, leading to PAD. Symptoms of PAD include leg pain, cramping, and weakness.
Pancreatitis: High levels of triglycerides in the blood, particularly very low-density lipoprotein (VLDL) triglycerides, can cause inflammation of the pancreas (pancreatitis), which can cause severe abdominal pain, nausea, and vomiting.
Yellowing of the skin and eyes: In rare cases, lipoprotein disorders that affect the liver can cause a condition called jaundice, which is characterized by yellowing of the skin and eyes.

It is important to note that lipoprotein disorders can be asymptomatic, and many people with high cholesterol or other lipoprotein abnormalities may not experience any symptoms. However, if left untreated, these disorders can increase the risk of serious health problems, including heart disease, stroke, and other cardiovascular events.

If you are concerned about your lipoprotein levels or have a family history of lipoprotein disorders, it is important to talk to your doctor and get your cholesterol and triglyceride levels checked regularly.

Treatment

The treatment for lipoprotein disorders depends on the type and severity of the disorder, as well as individual patient factors. Here are some common treatments for lipoprotein disorders:

Lifestyle modifications: Lifestyle modifications are often the first line of treatment for lipoprotein disorders. This includes regular exercise, a healthy diet low in saturated and trans fats, weight loss (if necessary), and avoiding smoking and excessive alcohol intake.
Medications: Several medications can help treat lipoprotein disorders. These include statins, which lower LDL cholesterol levels; niacin, which lowers LDL and triglyceride levels and raises high-density lipoprotein (HDL) cholesterol levels; fibrates, which lower triglyceride levels and raise HDL cholesterol levels; and bile acid sequestrants, which lower LDL cholesterol levels.
Apheresis: In severe cases, apheresis may be used to remove lipoproteins from the blood. This is a process where the patient’s blood is filtered through a machine that removes the lipoproteins, and the blood is then returned to the patient.
Surgery: In rare cases, surgery may be necessary to treat lipoprotein disorders. This may include procedures such as angioplasty or bypass surgery to treat atherosclerosis, or liver transplant to treat certain liver disorders that affect lipoprotein metabolism.

It is important to note that lipoprotein disorders are often chronic conditions that require ongoing management. Treatment may need to be adjusted over time based on changes in the patient’s lipoprotein levels, overall health, and response to treatment. Patients with lipoprotein disorders should work closely with their healthcare providers to develop a treatment plan that is tailored to their individual needs and goals.

Complications

Lipoprotein disorders can lead to a range of complications, particularly if left untreated. Here are some potential complications of lipoprotein disorders:

Atherosclerosis: Lipoprotein disorders that result in elevated levels of LDL cholesterol can contribute to the development of atherosclerosis, which is the buildup of plaque inside the arteries. Over time, this plaque can narrow the arteries, restrict blood flow, and increase the risk of heart attacks, strokes, and other cardiovascular problems.
Peripheral artery disease (PAD): Lipoprotein disorders that lead to atherosclerosis can also affect the blood vessels in the legs, leading to PAD. This condition can cause leg pain, cramping, and weakness, and can increase the risk of foot ulcers and amputations.
Pancreatitis: High levels of triglycerides in the blood, particularly very low-density lipoprotein (VLDL) triglycerides, can cause inflammation of the pancreas (pancreatitis), which can cause severe abdominal pain, nausea, and vomiting.
Xanthomas: Xanthomas are yellowish, fatty deposits that can develop on the skin and tendons, particularly around the eyes, elbows, knees, and heels. They are a sign of high cholesterol and can be a symptom of lipoprotein disorders.
Increased risk of heart disease and stroke: Lipoprotein disorders that result in elevated levels of LDL cholesterol and triglycerides can increase the risk of heart disease, strokes, and other cardiovascular problems.
Liver disease: Certain lipoprotein disorders can affect the liver and lead to liver disease, including nonalcoholic fatty liver disease (NAFLD) and cirrhosis.

Check out Ultimate USMLE Step 1 Study Notes.

Lipoprotein Disorders