Sitosterolemia is an autosomal recessive genetic disorder in which those affected experience an excessive accumulation of phytosterols in the blood and tissues. If left untreated, it can lead to premature cardiovascular events and hematological deficiencies.

What are phytosterols?

Phytosterols are various sterols and stanols from plant matter. Sterols are essentially steroidal lipids, and the most commonly known is cholesterol, which is produced in animals. Phytosterols are produced in plants, but function very similarly to cholesterol.

What's the main purpose of phytosterols?

One of the functions of sterols is to maintain the structure of cells, and the main function of phytosterols, it seems, is to maintain the cellular structure of the plant.

In humans, however, phytosterols serve as a protective agent against absorbing too much dietary cholesterol into the system. A diet high in cholesterol can lead to elevated levels in the blood and thus poor cardiovascular health. Phytosterols help keep dietary cholesterol from entering into the blood stream by binding to cholesterol, allowing our bodies to push both out of our systems.

How do phytosterols help lower cholesterol?

Phytosterols and cholesterol have a very similar chemical structure. In order for either to be absorbed, their molecules must bind together in the small intestine to form a micelle. Once they do so, the lumen in the intestine will recognize and absorb them.

The human body is animal-based and in fact produces its own cholesterol in the liver for various uses in the body. It cannot use phytosterols (chemical structure is different enough from cholesterol), recognizes them as poisonous, and pushes them back out of the system to be discarded with other waste in the intestines. When phytosterols are absorbed from the lumen into the bloodstream, special transporter proteins the body produces takes them back through the lumen to the gut. The liver can also process loose phytosterols in the blood by excreting them to the intestine through bile.

Though they are slightly chemically different, cholesterol and phytosterols are similar enough that they can bind together to form a micelle for absorption by the lumen. When they do so, the body recognizes that the micelle has phytosterols and tries to push them, along with the cholesterol, back out of the system via protein transporters. For a demonstration, watch this video.

So, phytosterols are good for me?

Generally, dietary phytosterols can have salubrious effects for most people, such as lowering cholesterol. However, phytosterols and other xenosterols (non-cholesterol sterols) are actually toxic if they enter the bloodstream and accumulate in the body and can impair cardiovascular health.

How do phytosterols accumulate in those with sitosterolemia?

People with sitosterolemia have a mutation in either or both the ABCG5 and ABCG8 genes. These genes are responsible for encoding transporter proteins (G5 and G8), which attach to and remove phytosterols from the body's system. The proteins that sitosterolemia patients produce are defective and thus insufficiently remove phytosterols, allowing them into the blood and passage into the rest of the body.

Is sitosterolemia a genetic disorder?

Yes, because of the presentation of mutations in the ABCG5/ABCG8 genes. The condition is autosomally recessive, and so those affected by sitosterolemia received a defective copy of the above genes from each parent.

What does "autosomal recessive" mean?

The genes we inherit from our parents come from either sex or autosome chromosomes. Sex chromosomes are specific to either the male or female type, Y or X respectively. Autosomes are generally sexless, but still pass on genetic information.

Recessive means that a trait from a gene is not dominant. Sitosterolemia is a recessive trait. Copies of genes exist in pairs on a chromosome, and their traits can be dominant or recessive. Dominant traits take over the development and presentation in the human body, even in the presence of a counter recessive trait on the other chromosome of the gene. For recessive traits to present in an individual, both copies of genes need to carry the recessive trait.

This video helps explain how dominant and recessive traits are inherited. Because it is recessive, sitosterolemia has a 25% chance of presenting in a child of two parents who are carriers (i.e. have one gene with the dominant copy, and one with the recessive). Most parents who pass on sitosterolemia to their children are likely carriers.

How many people have sitosterolemia?

There have been about 100 cases reported world-wide in the medical literature, but doctors believe the condition is significantly under-diagnosed.

What are the main symptoms of sitosterolemia?

The main symptoms are the appearance of xanthomas (superficial raised lipid-rich bumps), high levels of liver enzymes, arteriosclerosis, coronary artery disease, stroke, hemolytic anemia, macrothrombocytopenia, and potentially infertility.

Patients may only present with hematological symptoms, which makes it difficult to distinguish from other conditions that cause similar symptoms.

How do phytosterols cause anemia?

Our blood cells actually use cholesterol to maintain their outer membrane structure. Because phytosterols are chemically similar to cholesterol, they can attach to blood cell membranes and act as cholesterol. However, their chemical bonds of difference lead phytosterols to dissolve the structure of the blood cells and destroy them.

Why is it called "sitosterolemia"?

There are various types of phytosterols. The main ones found in plant matter are sitosterol, campesterol, and stigmasterol. Sitosterol is the most commonly occurring, hence the name of the condition.