Sitosterolemia - Causes, Symptoms, Diagnosis, and Treatment

Introduction:

Sitosterolemia is a rare genetic disorder in which fats or lipids from plant-based foods like nuts and vegetable oils accumulate in the blood and body tissues. The fats that accumulate are called phytosterols or plant sterols. There are several types of plant sterols, out of which sitosterol is commonly accumulated in the body, causing the blood levels to increase 30 to 100 times the average level. In addition, cholesterol is a type of animal fat that deposits in the body in some people with sitosterolemia. The body takes up plant sterols through food. People start showing signs and symptoms once the foods are introduced into their diet. However, certain people may not show any features.

What Are the Other Names of Sitosterolemia?

The other names of the condition include:

• Phytosterolemia.

• Phytosterolemia.

• Sitosterolemia.

• Beta-sitosterolemia.

• Plant sterol storage disease.

How Common Is Sitosterolemia?

Sitosterolemia is an extremely rare genetic disorder that occurs in one in 50,000 people. Only about 80 to 100 cases have been documented in the medical literature, as many patients go unnoticed due to mild symptoms.

What Are the Causes of Sitosterolemia?

The main cause of the occurrence of sitosterolemia is genetic change (mutations). For example, a defect in the gene ABCG5 or ABCG8 is responsible for plant fat accumulation in the body. The body cannot use plant sterols or fats. In normal people, the body sends out the sterols with the help of a protein called sterolin, a transporter protein that helps remove plant sterols from the cells. Sterolin is found mainly in the cells of the intestine and the liver. When the intestine cells take up the plant sterols, the transporter protein, sterolin, helps pump the plant fats back into the intestine, thereby decreasing the absorption.

The fats in the liver cells are removed by moving them into the fluid called bile, which then moves the fats into the intestines, to be removed by the feces. ABCG5 and ABCG8 are the genes that give instructions to make the protein sterolin. The condition is inherited as an autosomal recessive pattern, which means one defective gene copy is transferred to the child from each parent. Therefore, the parents have two copies of genes in each cell, out of which one copy is normal, and the other is defective. As the parents have one normal copy each, they are called carriers, but they do not show any signs and symptoms.

What Are the Symptoms of Sitosterolemia?

People affected with sitosterolemia mostly show the following signs and symptoms that include:

• Atherosclerosis: Blocking the artery wall by fatty deposits can occur in patients with sitosterolemia in early childhood, which eventually causes the narrowing of blood vessels, increasing the chance of stroke, heart attack, and death.

• Xanthomas: People with sitosterolemia develop yellowish growths on or below the skin, called xanthomas, occurring commonly from childhood. Xanthomas are made up of fats that can occur anywhere on the skin, mainly on the elbows, buttocks, knees, and heels. They can also occur in the tendons, which connect the bones to the muscles, commonly involving the Achilles tendon (connecting the heel to the calf muscles). Big xanthomas can cause pain and difficulty moving or walking.

• Joint Stiffness: Accumulation of plant-based fat deposits in the joints can lead to pain and stiffness of the joints.

• Blood Abnormalities: Though rare, blood abnormalities can occur in people with sitosterolemia, they are the only sign of sitosterolemia sometimes. The red blood cells (RBCs) that carry oxygen may break down early, causing a type of anemia called hemolytic anemia. Occasionally, abnormally shaped red blood cells (coffee bean-shaped instead of disc-shaped) occur in the bloodstream called stomatocytes. In addition, blood cells that help blood clot, called platelets, may be abnormally large, called macrothrombocytopenia.

How Is Sitosterolemia Diagnosed?

The normal level of the protein sitosterol in blood plasma is 1 mg/dL (milligrams per deciliter). Any value above 1mg/dL is diagnostic of sitosterolemia. The values of people who do not receive treatment may be as high as 10 to 65 mg/dL. A particular blood test called GC-MS (gas-chromatography-mass spectrometry) helps to determine elevated phytosterol levels, diagnosing sitosterolemia. The condition is confirmed in people with high blood levels of plant sterols like sitosterol, campesterol, and stigmasterol. Genetic testing that helps in determining the changes in the genes ABCG8 and ABCG5 is also recommended.

How Is Sitosterolemia Treated?

The goal of treatment is to bring back the levels of plant sterols in blood to near normal, reduce the levels of blood cholesterol, reduce the size of xanthomas, and prevent the formation of new xanthomas.

The therapies that are followed include:

• Dietary Changes: Doctors recommend a diet with foods containing fewer plant sterols.

• Medications: Tablet Ezetimibe 10 mg daily is the standard therapy doctors advise. It acts by reducing the amount of plant sterols and cholesterol absorbed by the body. If well tolerated, the tablet may also be combined with other medications that act better. Combination therapies have been shown to decrease the levels of sitosterol and cholesterol by 10 to 50 percent. However, Ezetimibe is not recommended for pregnant patients as studies are still in progress on the fetal effects.

• Bile Acid Sequestrants: Bile acid sequestrants like Cholestyramine are included in the treatment for cases that do not respond to Ezetimibe. They bind the plant sterols to bile juice, which helps excrete the sterols through stools.

• Sitosterolemia does not respond well to statin treatment as to other types of cholesterol in the body. Treatment is given for blood and joint disorders according to the symptoms.

What Is the Recommended Diet for Sitosterolemia Patients?

Dietary changes are advised along with Ezetimibe therapy, in which patients have to stop or reduce the foods containing plant sterols, like:

• Vegetable oils.

• Nuts and seeds.

• Avocados.

• Olives.

• Chocolates.

• Shellfish.

• Sources of vegetable fats.

Conclusion:

Sitosterolemia is when plant-based sterols accumulate in the blood vessels and tissues beneath the skin. As it is a very rare condition, the outlook is not predictable. However, early diagnosis and the start of treatment lead to better results. Delayed or untreated cases can increase the risk of complications and death in affected people. The availability of the medicine, Ezetimibe, has helped the patients lead a better quality of life.