What is Lecithin-Cholesterol Acyltransferase Deficiency?

Lecithin cholesterol acyltransferase (LCAT) deficiency is a rare condition that people can inherit from their parents. This condition results from the partial or complete lack of a specific enzyme known as LCAT. This enzyme is normally found in two types of particles in our blood, known as high-density lipoprotein (HDL) and low-density lipoprotein (LDL).

The LCAT enzyme has a critical role: it helps process cholesterol, which is an essential step for the normal function of HDL particles in our body. If you are lacking LCAT, the method your body uses to process HDL is disrupted. This disruption can lead to unusual levels of lipids (fats) in your body and can increase your risk of certain complications.

There are two main types of LCAT deficiency. The first is called familial LCAT deficiency, and it refers to a complete absence of the LCAT enzyme. The second type is known as Fish-eye disease, which is named this way because of certain eye symptoms it causes, and it results from a partial lack of the LCAT enzyme.

What Causes Lecithin-Cholesterol Acyltransferase Deficiency?

LCAT deficiency is a disease that you inherit from your parents. It happens due to changes, or mutations, in a gene called LCAT, which is located on chromosome 16 (16q22). Depending on the type of mutation, it can either cause a total lack of a working LCAT enzyme, known as familial LCAT deficiency, or it can cause the enzyme activity to reduce partially, which is called Fish-eye disease.

Risk Factors and Frequency for Lecithin-Cholesterol Acyltransferase Deficiency

LCAT deficiency is a very rare disease, so rare that only a few hundred cases have been reported across the entire globe. It’s so rare, in fact, that it’s estimated to only affect about 1 in every 1,000,000 people. Because it’s so uncommon, it’s hard to say if it affects certain genders or ethnicities more than others.

Signs and Symptoms of Lecithin-Cholesterol Acyltransferase Deficiency

Familial LCAT deficiency and Fish-eye disease are two different types of health issues. People suffering from each of these conditions can exhibit different symptoms.

When we talk about familial LCAT deficiency, people could experience various symptoms. These include:

Cloudy vision caused by corneal opacities (tiny greyish spots spread across the cornea)
Kidney problems or renal insufficiency
Lowering of red blood cells or hemolytic anemia
Symptoms related to atherosclerosis, a condition where arteries get narrow due to fats
Yellowish patches of cholesterol around eyes or xanthelasmata
Enlarged liver, a condition called hepatomegaly
Splenomegaly, which means an swollen spleen
Swollen lymph nodes or lymphadenopathy

On the other hand, people with Fish-eye disease usually have milder symptoms. The primary issue they face is impaired vision due to corneal opacities. However, similar to Familial LCAT deficiency, some might also display symptoms of an enlarged liver, swollen spleen, and swollen lymph nodes. It’s worth mentioning that with Fish-eye disease, corneal opacification, which clouds the cornea, can be significantly severe.

Testing for Lecithin-Cholesterol Acyltransferase Deficiency

Arriving at a diagnosis often relies on lab results, in addition to a doctor’s observations and the symptoms a person presents.

People with complete LCAT deficiency, a rare genetic disorder that affects the body’s ability to process fats, often show signs of a specific type of anemia where their blood cells are of normal size and color but appear as target cells. This condition is associated with an excess of an enzyme called lactate dehydrogenase, increased levels of bilirubin (a product of red blood cells) and lower than normal levels of a protein called haptoglobin in their blood. In addition, their kidney function may be compromised, with blood tests showing higher than normal levels of blood urea nitrogen, plasma creatinine, and protein in the urine, and lower rates of creatinine clearance which is an indicator of how well kidneys are filtering waste.

The key to diagnosing LCAT deficiency lies in the person’s lipid panel, a test that measures the amount of certain fats and cholesterol in the body. For people with LCAT deficiency, this panel indicates extraordinarily low levels of good cholesterol (usually less than 10 mg/dL), increased levels of VLDL (a type of bad cholesterol), and triglycerides (another type of fat), elevated levels of unesterified (unprocessed) cholesterol, and lower levels of esterified (processed) cholesterol in the blood. Additionally, the activity of the LCAT enzyme, responsible for processing certain fats in the bloodstream, would be noticeably low or absent.

On the other hand, Fish-eye disease, another rare genetic disorder with some similarities to LCAT deficiency, presents differently in lab tests. This disease is identified by low levels of good cholesterol (around 10% of what’s considered normal), increased levels of VLDL and triglycerides, higher concentrations of unesterified cholesterol in good cholesterol, and decreased amounts of esterified cholesterol in good cholesterol. Unlike LCAT deficiency, in this disease, the total cholesterol remains normal. Additionally, the body is unable to process a radioactive form of cholesterol in certain fats or good cholesterol except for in bad cholesterol. There are typically no abnormalities related to blood or kidney function in Fish-eye disease patients.

It’s important to note that most standard laboratories cannot measure LCAT activity. Therefore, a specialized center is typically required for a definitive diagnosis of these conditions.

Treatment Options for Lecithin-Cholesterol Acyltransferase Deficiency

LCAT deficiency is a health condition with no definite cure currently. However, it can be managed by concentrating on mitigating its complications. This is done through changes in diet, regular exercise, medications to lower cholesterol, and blood pressure medications, mainly ACE-Is (medications that help relax veins and arteries to lower blood pressure) or ARBs (drugs that block the chemical that narrows the blood vessels). These lifestyle and medication adjustments form the backbone of treatment and can slow down the progression of the disease. Furthermore, corticosteroid therapy (drugs that reduce inflammation) might be a beneficial treatment choice.

If the disease progresses to a phase known as end-stage renal disease, which means kidneys are no longer able to work as needed on their own, options such as dialysis and kidney transplantation are suggested. Even though the disease may reappear in patients who received a kidney transplant, it’s important to know these individuals typically witness satisfactory long-term results.

In terms of future treatment possibilities, studies are being conducted into the use of gene and enzyme replacement therapy using the human LCAT enzyme. A study revealed positive outcomes with this method, showing improvements in anemia and kidney function, and temporary correction of lipid abnormalities (irregular cholesterol or fat levels in the blood).

When diagnosing LCAT deficiency, a rare genetic condition that affects cholesterol levels in the body, doctors have to rule out other conditions with similar symptoms. These conditions include:

Familial hypercholesterolemia: A condition that’s inherited and leads to high levels of ‘bad’ cholesterol (LDL-C), which can cause early heart disease.
Tangier Disease: A genetic disorder which drastically lowers ‘good’ cholesterol (HDL) levels, leading to a yellow or orange color in the tonsils, enlarged liver and spleen, and nerve damage.
Niemann-Pick disease: A genetic disorder that results in the buildup of harmful substances in the body, causing an enlarged liver and spleen, and spots in the eyes that are cherry red.
Hypertriglyceridemia: A condition characterized by high levels of triglycerides or fats in the blood, leading to inflammation of the pancreas, heart disease, and small, yellowish deposits of fat in the skin (palmar xanthomas).
Familial HDL deficiency: An inherited disorder with low levels of ‘good’ cholesterol and a higher risk of early-onset heart disease. Unlike LCAT deficiency, this condition typically does not lead to cloudy corneas and kidney problems.
Abetalipoproteinemia: A rare genetic disorder that results in very low or absent levels of cholesterol, LDL, and VLDL. Symptoms of this disease include peculiarly shaped red blood cells (acanthocytes), inability to absorb fats from food, damage to the part of the brain that coordinates movement (spinocerebellar degeneration), and progressive vision loss (retinitis pigmentosa).

Each of these conditions has its own unique features, and understanding them can help in making a correct diagnosis.

What to expect with Lecithin-Cholesterol Acyltransferase Deficiency

The future health outcomes, or prognosis, for someone with LCAT deficiency largely depends on how severe their genetic mutation is. LCAT deficiency is a condition that affects the body’s ability to process certain fats.

If the deficiency is complete, it tends to be a more severe disease that shows up early in childhood, with strong symptoms. However, if the deficiency is only partial, the symptoms are usually milder and don’t show up until later in life.

This condition is quite rare, so we don’t have a lot of information about how likely it is to cause death. As more research is conducted, we’ll learn more about the mortality rates associated with LCAT deficiency.

Possible Complications When Diagnosed with Lecithin-Cholesterol Acyltransferase Deficiency

People with LCAT deficiency can experience various complications depending on the extent of their deficiency. If the LCAT deficiency is complete, one common symptom is proteinuria, a condition that suggests the kidneys aren’t functioning correctly. This could get worse over time, leading to kidney failure. In such cases, treatments like dialysis or kidney transplants might be necessary.

On the other hand, individuals with only a partial LCAT deficiency often suffer from corneal opacification. This condition is caused by cholesterol building up in the eyes, which can significantly impair vision.

Regardless of whether the LCAT deficiency is complete or partial, the condition disrupts the process by which HDL – the “good” cholesterol – regulates cholesterol transport in the body. This disruption can lead to dyslipidemia, a disorder of lipoprotein metabolism. In turn, this increases the risk of developing hardening of the arteries, known as atherosclerosis. This can make the individual more likely to suffer cardiovascular events, including heart attacks or strokes.

Common complications:

Proteinuria – indicating kidney dysfunction
Renal failure – potentially requiring dialysis or a kidney transplant
Corneal opacification – leading to significant visual impairment
Dyslipidemia – due to disrupted regulatory role of “good” cholesterol in cholesterol transport
Atherosclerosis – increased hardening of the arteries due to raised cholesterol levels
Potential cardiovascular events – such as heart attacks and strokes.

Preventing Lecithin-Cholesterol Acyltransferase Deficiency

HDL, commonly referred to as ‘good cholesterol’, plays a crucial role in guarding against severe heart-related incidents like heart attacks and strokes. It does this by taking away cholesterol from various tissues in the body and transporting it to the liver to be broken down and used by our body. Additionally, HDL has some special features such as the ability to reduce inflammation, improve the functioning of endothelial cells (the cells that line the inside of our heart and blood vessels), and prevent the formation of blood clots.

It’s very important to lead a healthy lifestyle to maintain good levels of HDL in our body. This can be achieved through regular aerobic exercise, eating a well-balanced diet full of nutritious food, and quitting smoking if you’re a smoker. Specific food recommendations exist for people who have a higher risk of developing heart disease. Foods rich in omega-3 fatty acids, a type of fat that is healthy for our heart, are especially useful in these cases. A perfect example of this kind of diet is the Mediterranean diet, which is primarily plant-based and is rich in healthy fats.