OVERVIEW

What is sitosterolemia?

Sitosterolemia, also known as phytosterolemia, stigmasterolemia, or beta-sitosterolemia, is a rare autosomal recessive genetic disorder.

This condition occurs due to gene mutations in the body, leading to increased intestinal absorption of plant sterols and reduced excretion through bile. As a result, blood levels of plant sterols (primarily sitosterol, campesterol, and stigmasterol) rise significantly, causing excessive accumulation in tissues and potential organ damage, which manifests in corresponding symptoms.

Clinical presentations vary among patients. Some may show almost no symptoms, while others may develop severe hyperlipidemia, leading to premature atherosclerosis or even fatal early-onset myocardial infarction.

Sitosterolemia is a manageable condition. Dietary adjustments, medication, and surgical interventions can significantly reduce plant sterol and cholesterol levels, promote xanthoma regression, and improve other symptoms. Early detection, diagnosis, and treatment are crucial for disease control.

Is sitosterolemia common?

Sitosterolemia is uncommon.

It is classified as a rare disease, with fewer than 200 reported cases worldwide, including over 20 documented cases in China.

SYMPTOMS

What are the manifestations of sitosterolemia?

Some patients may have almost no symptoms, while symptomatic individuals may exhibit manifestations such as xanthomas, atherosclerosis, blood disorders, and liver damage.

• Xanthomas: These are the primary clinical manifestations of sitosterolemia, often appearing early in life, sometimes even within the first year after birth. Since minor trauma plays a significant role in the development of xanthomas, they typically occur on the extensor surfaces of the limbs, such as the Achilles tendon, extensor tendons of fingers/toes, elbows, and knees, where collisions are more likely. In infants, who are less active and have a lower risk of skin injury, friction in skin folds—especially in obese infants—may lead to xanthomas in these areas, while extensor regions are less commonly affected.
• Atherosclerosis: Related manifestations include coronary plaque rupture and thrombosis, which are major causes of acute myocardial infarction and sudden cardiac death.
• Blood disorders: Such as anemia (stomatocytic hemolytic anemia) and macrothrombocytopenia, often accompanied by splenomegaly and abnormal bleeding.
• Liver damage: Including liver dysfunction and cirrhosis.
• Others: Cases of arthritis or arthralgia have also been reported.

What serious complications can sitosterolemia cause?

Sitosterolemia may lead to acute myocardial infarction, and in severe cases, sudden cardiac death.

This is primarily due to significantly elevated levels of plant sterols and cholesterol in the blood, which contribute to the development of atherosclerotic plaques. If coronary plaque rupture and thrombosis occur, myocardial infarction may result.

CAUSES

What is the cause of sitosterolemia?

The cause of sitosterolemia is a mutation in the body's genes (ABCG5 or ABCG8 genes), which leads to increased intestinal absorption of plant sterols and reduced excretion through bile. This results in a significant rise in plant sterols (mainly including sitosterol, campesterol, stigmasterol, etc.) in the blood, as well as excessive accumulation in other tissues, causing organ damage and corresponding symptoms.

Is sitosterolemia a genetic disease? How is it inherited?

Sitosterolemia is a genetic disease.

It follows an autosomal recessive inheritance pattern, characterized by:

• If a patient marries someone with a normal genotype, all their children will be normal;
• If a patient marries a "normal" carrier (with one disease-causing gene), their children have a 50% chance of inheriting the disease;
• If two "normal" carriers marry, their children have a 25% chance of inheriting the disease;
• If two patients marry, 100% of their children will inherit the disease, with equal chances for boys and girls.

DIAGNOSIS

What tests are needed to diagnose sitosterolemia?

For suspected sitosterolemia, the main tests are plant sterol testing and genetic testing.

• Plant sterol testing: Gas chromatography (GCMS) or high-performance liquid chromatography is used to quantitatively measure the levels of plant sterols (such as sitosterol, campesterol, and stigmasterol) in the blood. Normal blood sitosterol levels range from 1–15 mg/L, while in sitosterolemia patients, the levels can be several times or even dozens of times higher.
• Genetic testing: ABCG5/ABCG8 gene testing is performed. If gene mutations are identified, a definitive diagnosis can be made in combination with clinical manifestations.

Which diseases is sitosterolemia easily confused with? How to differentiate them?

Sitosterolemia is often confused with ordinary hypercholesterolemia.

For patients diagnosed with hypercholesterolemia, if their parents have normal blood cholesterol levels or do not exhibit the autosomal dominant inheritance pattern typical of familial hypercholesterolemia, sitosterolemia should be suspected.

Differentiation can be achieved through plant sterol and genetic testing. Sitosterolemia is characterized by significantly elevated plant sterol levels and detectable gene mutations, whereas ordinary hypercholesterolemia lacks these features.

TREATMENT

Which department should I visit for sitosterolemia?

For sitosterolemia, you should visit the pediatric or endocrinology department.

Can sitosterolemia be completely cured?

No.

Sitosterolemia is a genetic disorder caused by gene mutations and cannot be completely cured. However, with proper treatment, the condition can be effectively managed to ensure the patient's quality of life and lifespan.

How is sitosterolemia treated?

Treatment for sitosterolemia mainly includes dietary adjustments and medication.

• Dietary adjustments: Limit the intake of plant sterols through dietary changes.
• Medication: Includes cholesterol absorption inhibitors, such as ezetimibe, currently considered the most effective drug; or bile acid sequestrants, such as cholestyramine. The two types of drugs can also be combined if necessary.
• Surgical treatment: Some patients may benefit from surgical interventions, such as ileal bypass surgery, to reduce intestinal absorption of plant sterols.

With these comprehensive treatment measures, plant sterol and cholesterol levels in patients can be significantly reduced, promoting the regression of xanthomas and improving other symptoms.

Is the mortality risk high for sitosterolemia?

Sitosterolemia carries a risk of sudden cardiac death, often occurring at a young age. The main cause of sudden cardiac death is acute myocardial infarction due to coronary plaque rupture and thrombosis.

However, there are currently no precise statistics on the specific mortality rate.

DIET & LIFESTYLE

What dietary precautions should patients with sitosterolemia take?

Patients with sitosterolemia should strictly limit the intake of plant sterols and avoid foods rich in plant sterols, including: vegetable oils, wheat germ, nuts, margarine, ghee, and chocolate. Shellfish and algae contain large amounts of algal plant sterols and should also be avoided.

Moderate restriction of animal sterol intake is recommended. Foods rich in animal sterols mainly include meat, eggs, dairy products, etc.

What lifestyle precautions should patients with sitosterolemia take?

Sitosterolemia is an incurable disease, so lifelong adherence to dietary and medication management is necessary.

Can patients with sitosterolemia get married and have children?

Yes.

Sitosterolemia does not affect fertility, but since it is a genetic disorder, the partner should be informed before marriage. Children are recommended to undergo hypercholesterolemia screening. If hypercholesterolemia is detected, further plant sterol testing and genetic testing may be necessary.

Can patients with sitosterolemia take care of themselves?

Yes.

Although sitosterolemia is an incurable disease, it is manageable. With dietary and medical treatment, the condition can be effectively controlled and stabilized, allowing patients to live independently without significant impact on daily life.

PREVENTION

Can Sitosterolemia Be Prevented? How to Prevent It?

Currently, sitosterolemia cannot be prevented.

The U.S. recommends screening children aged 9–11 for hypercholesterolemia and conducting another screening for adolescents aged 17–21. If a patient with hypercholesterolemia has parents with normal blood cholesterol levels or does not meet the criteria for autosomal dominant familial hypercholesterolemia, further testing is needed to rule out sitosterolemia.

Early diagnosis and appropriate treatment can lead to effective outcomes and a favorable prognosis.