Sitosterolemia

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Sitosterolemia is a condition in which fatty substances (lipids) from vegetable oils, nuts, and other plant-based foods accumulate in the blood and tissues. These lipids are called plant sterols (or phytosterols). Sitosterol is one of several plant sterols that accumulate in this disorder, with a blood level 30 to 100 times greater than normal. Cholesterol, a similar fatty substance found in animal products, is mildly to moderately elevated in many people with sitosterolemia. Cholesterol levels are particularly high in some affected children. However, some people with sitosterolemia have normal cholesterol levels.

Plant sterols are not produced by the body; they are taken in as components of foods. Signs and symptoms of sitosterolemia may begin to appear early in life after foods containing plant sterols are introduced into the diet, although some affected individuals have no obvious symptoms.

In people with sitosterolemia, accumulation of fatty deposits in arteries (atherosclerosis) can occur as early as childhood. These deposits narrow the arteries and can eventually block blood flow, increasing the chance of a heart attack, stroke, or sudden death.

Some people with sitosterolemia develop small yellowish growths called xanthomas beginning in childhood. Xanthomas consist of accumulated lipids and may be located anywhere on or just under the skin, typically on the heels, knees, elbows, and buttocks. They may also occur in the bands that connect muscles to bones (tendons), including tendons of the hand and the tendon that connects the heel of the foot to the calf muscles (the Achilles tendon). Large xanthomas can cause pain, difficulty with movement, and cosmetic problems.

Joint stiffness and pain resulting from plant sterol deposits may also occur in individuals with sitosterolemia. Less often, affected individuals have blood abnormalities. Occasionally the blood abnormalities are the only signs of the disorder. The red blood cells may be broken down (undergo hemolysis) prematurely, resulting in a shortage of red blood cells (anemia). This type of anemia is called hemolytic anemia. Affected individuals sometimes have abnormally shaped red blood cells called stomatocytes. In addition, the blood cells involved in clotting, called platelets or thrombocytes, may be abnormally large (macrothrombocytopenia).

ORPHANET DEFINITION Sitosterolemia is a rare autosomal recessive sterol storage disease characterized by the accumulation of phytosterols in the blood and tissues. Clinical manifestations include xanthomas, arthralgia and premature atherosclerosis. Hematological manifestations include hemolytic anemia with stomatocytosis and macrothrombocytopenia. The disease is caused by homozygous or compound heterozygous mutations in ABCG5 (2p21) and ABCG8 (2p21) genes.

Inheritance

From: MedlinePlus Genetics, National Library of Medicine

Autosomal recessive

Frequency in the source

From: MedlinePlus Genetics, National Library of Medicine

Reported case(s): 100.0; Worldwide. This is a published case count, not prevalence. Point prevalence: <1 / 1 000 000; Worldwide; Class only.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Arthralgia · Frequent (79-30%)

Joint pain.

Elevated circulating hepatic transaminase concentration · Frequent (79-30%)

Elevations of the levels of SGOT and SGPT in the serum. SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic transaminase) are transaminases primarily found in the liver and heart and are released into the bloodstream as the result of liver or heart damage. SGOT and SGPT are used clinically mainly as markers of liver damage.

Elevated circulating sitosterol concentration · Frequent (79-30%)

An increased concentration of beta-sitosterol in the blood circulation.

Giant platelets · Frequent (79-30%)

Giant platelets are larger than 7 micrometers and usually 10 to 20 micrometers. The term giant platelet is used when the platelet is larger than the size of the average red cell in the field. (Description adapted from College of American Pathologists, Hematology Manual, 1998).

Hemolytic anemia · Frequent (79-30%)

A type of anemia caused by premature destruction of red blood cells (hemolysis).

Hypercholesterolemia · Frequent (79-30%)

An increased concentration of cholesterol in the blood.

Premature coronary artery atherosclerosis · Frequent (79-30%)

Reduction of the diameter of the coronary arteries as the result of an accumulation of atheromatous plaques within the walls of the coronary arteries before age of 45.

Splenomegaly · Frequent (79-30%)

Abnormal increased size of the spleen.

Stomatocytosis · Frequent (79-30%)

The presence of erythrocytes with a mouth-shaped (stoma) area of central pallor on peripheral blood smear.

Xanthomatosis · Frequent (79-30%)

The presence of multiple xanthomas (xanthomata) in the skin. Xanthomas are yellowish, firm, lipid-laden nodules in the skin.

Macrothrombocytopenia · Frequent (79-30%)

Aortic valve stenosis · Occasional (29-5%)

The presence of a stenosis (narrowing) of the aortic valve.

Arthralgia/arthritis · Occasional (29-5%)

When it may begin

From: MedlinePlus Genetics, National Library of Medicine

All ages

Inheritance in the source

From: MedlinePlus Genetics, National Library of Medicine

Autosomal recessive

Frequency and the population described

From: MedlinePlus Genetics, National Library of Medicine

Reported case(s): 100.0; Worldwide. This is a published case count, not prevalence. Point prevalence: <1 / 1 000 000; Worldwide; Class only.

Understanding the inheritance label

From: MedlinePlus Genetics

An autosomal recessive pattern usually involves disease-causing changes in both copies of a gene. Parents may each carry one altered copy without having the condition themselves. A genetic counsellor can explain carrier testing and reproductive implications using the actual laboratory findings, rather than the condition name alone.

Which doctor should you see?

The suggested department for discussing Sitosterolemia is Metabolic Medicine, with a metabolic specialist / clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with metabolic specialist / clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Is a biochemical or molecular result needed to clarify the diagnosis?
• Does this condition require an individual plan for illness or reduced food intake?
• Should nutrition advice come from a specialist metabolic dietitian?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Sitosterolemia. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.