What is Sitosterolemia?

Sitosterolemia is an inherited disorder in which waxy substances from plants are absorbed into the body and build up in the blood and arteries. These waxy substances are called “plant sterols”. The principle one is sitosterol. Usually, plant sterols are separated from the healthy nutrients of these foods and are cleared from the intestine before ever entering the body. This is done by a protein “pump” called ABCG5/ABCG8. Sitosterolemia develops when the gene responsible for the creation of this pump is broken.

The condition is “recessive” which means that a broken copy of the gene must be inherited from each parent. The parents, who only have one broken copy of the gene, do not have the disorder.


How common is it?

Only about 100 people with sitosterolemia have been reported. However, researchers believe that sitosterolemia may affect as many as 1 in 50,000 people that have not yet been diagnosed. If left undiagnosed and unmanaged, sitosterol can build up over time in arteries and cause a heart attack and/or stroke.

What are the symptoms?

The condition is usually first seen in childhood. People with the condition have sitosterol levels that are at least 10x greater than the usual blood level. In addition to sitosterol, cholesterol levels are often very high because the same “pump” which is supposed to eliminate plant sterols also gets rid of around 50% of the cholesterol in the diet. The good news is patients with sitosterolemia can dramatically lower their blood cholesterol by eating a low cholesterol diet. A dramatic drop in high blood cholesterol with a low cholesterol diet is a clue to the diagnosis of sitosterolemia.

Other forms of genetic high blood cholesterol do not respond so dramatically to diet alone, without medication.

In addition to high blood cholesterol level, large lumps of cholesterol, called “xanthomas” (zan-tho-muhs), can appear on the elbows, knees and the Achilles tendon above the heel. Another symptom can be anemia, caused by plant sterols in the walls of red blood cells making them likely to break apart. Platelets – the cells in the blood which help prevent bleeding – can also be low in number and larger than usual. People with sitosterolemia may also experience joint stiffness and pain.

How is it treated?

While there is no cure for this disorder, symptoms CAN be controlled by reducing intake of plant sterols as well as by following a low-cholesterol diet. Foods high in plant sterols that should be avoided include some legumes (dried peas, beans, lentils, peanuts, almonds, walnuts, pecans, sunflower seeds, pumpkin seeds and sesame seeds) some fruits and vegetables (oranges, apples, berries, avocado, broccoli, cauliflower, brussels sprouts), vegetable oils, wheat germ oils, and shellfish. However, diet alone is not enough. Several medications lower blood sitosterol levels by decreasing absorption. A drug called “ezetimibe” has been shown to lower blood sitosterol levels by 44% and medications called “bile acid sequestrants” give a 30% reduction.

Jacob’s Story

A 58-year-old patient Jacob (name changed for patient’s privacy) was referred to Dr. Alan Brown’s lipid clinic in Chicago for statin intolerance and a history of “genetic hypercholesterolemia.” He had tendon xanthomas on his hands (see photo) and on his Achilles tendons (back of his heels) since childhood. Jacob had a biopsy of his Achilles tendon that revealed “cholesterol” deposits. He was not able to take statin therapy (simvastatin, atorvastatin, pravastatin, or rosuvastatin) that was prescribed to him because of the side effect of muscle aches.

Jacob was not on lipid-lowering drugs at the time of his first visit with Dr. Brown. At the time, his LDL (“bad”) cholesterol was 169 mg/dL. He had moderate build up of plaque in one of the arteries in his neck but had never had a heart attack or a stroke. He was a smoker and had a significant family history of premature heart attacks in several of his siblings. He was overweight. He did not have high blood pressure or diabetes.

Dr. Brown noted the xanthomas and the LDL cholesterol which was only moderately elevated and considered the possibility of sitosterolemia. Jacob was on ezetimibe, which, on average, lowers sitosterol levels in the blood by 44% when his sitosterol came back from the lab at 6.6 mg/dL. That means that his untreated would have been around 11.8 mg/dL. Normal sitosterol is under 0.5mg/dL so his untreated level was 20 times normal!

Although most of the patients with sitosterolemia who have been reported in medical journals were diagnosed in childhood, this case shows that the diagnosis can be missed well into adulthood.

A major clue to the diagnosis in this patient was that fact that he had xanthomas with only a very mildly elevated LDL cholesterol (169mg/dL). If this patient had the more typical cause of xanthomas- familial hypercholesterolemia- his LDL cholesterol would have been 250mg/dL or higher! There is also another very rare cause of xanthomas called cerebrotendinous xanthomatosis (CTX). CTX was ruled out because Jacob wasn’t experiencing any neurologic symptoms, diarrhea, cataracts or seizures, which are all common in people with CTX.

The normal range of sitosterol in the blood is up to 0.5 mg/dL or 5.0 mg/L. The difference is whether the amount present in 100 milliliters (one tenth of a liter) or 1000 milliliters (a full liter) is reported.



Caleb’s Story

When Caleb was five years old, his pediatrician checked his cholesterol level. It came back over 300mg/dL. This was a surprise to his parents since neither of them had high cholesterol. Although the pediatrician wanted to start a statin medication, his mother preferred to try diet first. In fact, the whole family went on a low cholesterol, low saturated fat diet. Caleb’s cholesterol dropped to 180! His mother felt like a supermom! As he got older it did go up but generally stayed in the 200 range.

However, when Caleb was 12, during kitchen remodeling, the family was eating a lot of fast food. A cholesterol check was 432 with this diet! At that point Caleb was put on a statin medication. It was expected that his cholesterol would fall into the low to mid 200 range with the statin but it remained in the 300s, despite going back on the healthy diet.

When Caleb was 13, his mother, frustrated by years of not knowing why Caleb had high cholesterol and uncertain how to make it better, began Googling cholesterol researchers. (She *is* a supermom!) She sent emails, not really expecting responses. However, she did get a response from Dr. Helen Hobbs in Texas who recommended Caleb be in a study. Blood samples were shipped to Dr. Hobbs and the diagnosis of sitosterolemia was made. His level of sitosterol was ten times normal.

At age 14, Caleb stopped taking the statin medication and started ezetimibe, a medication which blocks the absorption of both cholesterol and sitosterol. Caleb’s cholesterol dropped to normal and his sitosterol level dropped 40%. He also started a diet low in plant sterols.

Caleb is now a young adult and is doing well. He is appreciative of all his supermom did for him!

Caleb never had xanthomas- lumps of cholesterol on Achilles tendons or tendons of the hand. This is often seen in sitosterolemia patients but not necessary for the diagnosis.

A clue to the diagnosis of sitosterolemia was the wild swings in Caleb’s blood cholesterol with diet alone- no medication. Sitosterolemia patients dramatically over absorb both cholesterol and plant sterols so limiting cholesterol in the diet (or consuming too much) has much more effect than in other people.

Another clue was the fact that neither of his parents had high cholesterol. This makes his very high cholesterol “recessive”. Sitosterolemia is one of the recessive forms of high cholesterol.

Finally, his cholesterol did not respond well to statin medications which is also typical of sitosterolemia.