Familial Hypertriglyceridemia

What is Familial Hypertriglyceridemia?

Familial hypertriglyceridemia (FHTG), also called type IV familial dyslipidemia, is a genetic disorder that causes the liver to produce too many very low-density lipoproteins (VLDL). This leads to high levels of triglycerides and VLDL in the blood. Triglycerides are a type of fat found in the blood, and VLDL is a type of protein that carries triglycerides and other fats. In FHTG, there’s a 50% chance for an affected person to pass the condition to their child. Recent studies suggest multiple gene variants contribute to the development of this condition.

Type IV familial dyslipidemia falls within a classification system developed by Donald Fredrickson in the 1960s and adopted by the World Health Organization (WHO). This system categorizes blood fat disorders into five major types based on which fats are too high.

People with FHTG typically have slightly elevated to moderate concentrations of triglycerides in their blood. They often have related health problems such as obesity, high blood sugar, and high blood pressure. Frequently, they have a mutation in a gene (lipoprotein lipase gene) that helps regulate fatty molecules, which can elevate triglyceride levels. Any underlying medication conditions or medicines they’re taking can make the triglyceride levels higher and possibly lead to a severe condition called acute pancreatitis (inflammation of the pancreas).

Importantly, it’s usually challenging to spot FHTG because there may be no symptoms until severe problems occur. Hence, it’s crucial to recognize symptoms like xanthomas (fatty deposits under the skin), an enlarged liver, or lipemia retinalis (a creamy appearance of the blood vessels in the eyes). Also, knowing the family’s medical history helps diagnose this disorder promptly. To manage FHTG effectively, it involves multiple strategies, including lifestyle changes and drug treatments.

What Causes Familial Hypertriglyceridemia?

Familial hypertriglyceridemia (FHTG) is a genetics-based disorder that causes high triglyceride levels in your blood. Triglycerides are a type of fat found in your blood that your body uses for energy. This issue arises from the overproduction of very-low-density lipoprotein (VLDL) particles in the liver, or from the overproduction of fat particles in the small intestine. While there are some cases of FHTG that are caused by alterations in a single gene, most come from changes in multiple genes (over 30 have been identified so far) and how they interact with environmental factors.

A particular gene often linked to FHTG is the LPL gene which creates an enzyme called lipoprotein lipase (LPL). If this gene is not working properly, it can affect the breakdown of fats from the VLDL particles and cause higher levels of triglycerides. Also, the hormone insulin helps activate LPL in body fat tissue. Therefore, individuals with insulin resistance – a condition where your body does not use insulin effectively – might have less LPL activity, which can make an existing FHTG condition even worse.

Too much triglyceride in the bloodstream affects more than just triglyceride levels; it also disrupts other fat measurements and contributes to unhealthy changes in fat metabolism and heart health. High triglyceride levels can change the composition and function of fat transport particles in your blood, leading to shifts in total cholesterol levels. This can result in the formation of smaller, denser low-density lipoprotein (LDL) particles, which cause more plaque build-up in the arteries than larger LDL particles. Therefore, each patient’s FHTG condition and how it presents can be different, which can be influenced by other health factors like obesity, insulin resistance, diabetes, alcohol consumption, and certain medications like oral estrogens.

Risk Factors and Frequency for Familial Hypertriglyceridemia

Familial hypertriglyceridemia (FHTG), a condition characterized by high levels of fat in the blood, affects around 1% of people overall. However, those who are obese, have insulin resistance, or a family history of certain heart diseases, may have a higher chance of developing FHTG. If there’s a case of premature heart disease in the family, the chance of having FHTG can increase up to 20%.

Different inherited changes or mutations in the LPL gene, which are involved in this condition, can be found in varying numbers of people, ranging from 0.06% to 20%. These changes can cause differences in the severity of the condition. FHTG also varies between different ethnic groups, with people of Hispanic and East Asian descent being more likely than those of African or European descent to develop this condition.

• Familial hypertriglyceridemia (FHTG) affects around 1% of the population in general.
• People who are obese, resistant to insulin, or have a family history of certain heart diseases are more likely to have it.
• The likelihood of having FHTG can increase up to 20% in families with premature heart disease instances.
• The presence of different inherited changes in the LPL gene varies from 0.06% to 20% of people. These changes can cause varying degrees of the condition.
• Hispanic and East Asian individuals are more likely to develop FHTG than persons of African or European descent.

Signs and Symptoms of Familial Hypertriglyceridemia

Familial Hypertriglyceridemia (FHTG) is a condition that is often inherited, although many people may not know their family’s medical history. This disorder typically doesn’t come with a family history of early heart disease, unless the person also has a related condition called Familial Combined Hyperlipidemia (FCHL). Patients may report diet habits high in fats and simple carbohydrates, as well as a lack of physical activity, which can worsen the condition.

People’s own medical history may not reveal much, except in cases where very high triglyceride levels have resulted in acute pancreatitis. Other health conditions that these patients might have and could further deteriorate their lipid levels include obesity, diabetes, or they could be taking certain medications that raise triglyceride levels. When suffering from acute pancreatitis, the individual usually experiences stomach pain, nausea, and vomiting.

Most patients with FHTG may not show any signs or symptoms. However, those with very high triglyceride levels can develop eruptive xanthomas, small (1-5 mm) red to yellow bumps, primarily present on the extensor surfaces of the extermities, bottom, and back. These xanthomas might be the only visible sign of extremely high triglyceride levels and they need to be identified and managed promptly to prevent complications like acute pancreatitis. A thorough skin check-up is recommended for all people with high triglycerides or associated conditions like metabolic syndrome or diabetes, to look for any signs of xanthomas.

People with severely high triglyceride levels can also develop chylomicronemia syndrome. This includes symptoms of:

• Short-term memory loss
• Hepatosplenomegaly (enlarged liver and spleen)
• Pancreatitis
• Shortness of breath
• Abdominal pain

In cases where the triglyceride levels are excessively high, often surpassing 2500 mg/dL, a condition called lipemia retinalis may develop. It is characterized by a creamy white discoloration of the retinal blood vessels due to lipid accumulation in the blood.

Testing for Familial Hypertriglyceridemia

To assess patients with Familial Hypertriglyceridemia (FHTG) – a condition characterized by high levels of a fat type known as VLDL, doctors usually take a detailed medical history, perform a complete physical examination and conduct specific laboratory tests. People with this condition have triglyceride (a type of fat in the blood) levels usually ranging from 200 to 1000 mg/dL and often show standard or low LDL (bad cholesterol) and high HDL (good cholesterol) levels. Typically, they don’t show any symptoms unless triglyceride levels exceed 500 mg/dL, which increases the risk of acute pancreatitis, an inflammation of the pancreas.

Endocrine Society’s clinical practice guidelines highlight the significance of differentiating FHTG from other similar conditions like Familial Combined Hyperlipidemia (FCHL), which are associated with a higher risk of early development of atherosclerotic cardiovascular disease (ASCVD), a disease in which plaque builds up inside arteries. FCHL often presents with elevated apoB or LDL cholesterol levels, which aren’t typically seen in FHTG.

After the medical history and physical examination, it’s important to get a fasting lipid profile, a blood test that measures lipids—fats and fatty substances in the blood. If the test results show elevated triglyceride levels without any known secondary causes, it suggests a genetic disorder. The severity of triglyceride levels is categorized as follows:

• Mild: 150 to 199 mg/dL
• Moderate: 200 to 999 mg/dL
• Severe: 1000 to 1999 mg/dL
• Very Severe: ≥2000 mg/dL

Doctors also examine for other potential related health conditions that could speed up the progression of this disease, like obesity, insulin resistance, diabetes, and cardiovascular disease. Other medical tests like hemoglobin A1c, fasting blood glucose, and liver and thyroid function tests could be taken when clinically necessary. It’s noticed that patients with FHTG are at risk of developing insulin resistance, which can lead to diabetes and make the existing high levels of blood fats worse. For patients at an increased risk of ASCVD, a basic electrocardiogram (ECG)–a test to check heart’s rhythm and electrical activity, is recommended. Doctors also need to identify secondary causes contributing to elevated triglyceride levels such as alcohol use, obesity, and certain medications.

While genetic testing is not usually needed, it can help differentiate FHTG from other genetic lipid disorders. Knowing specific genes linked to triglyceride metabolism can help with a precise diagnosis. Family members of patients should be aware of their fasting lipoprotein profile and receive counseling, but currently, routine genetic testing is not advised. The primary way to evaluate patients with FHTG and their at-risk family members is through a thorough personal and family medical history, careful physical examination, fasting lipoprotein profiles, and assessment of any secondary factors worsening the high triglyceride levels.

Treatment Options for Familial Hypertriglyceridemia

Treating Familial Hypertriglyceridemia (FHTG), a condition characterized by high levels of fat particles in the blood, takes a multi-step process that aims to bring down these fat levels. This is done to lessen the chances of having acute pancreatitis or ASCVD, a disease where fat deposits on the walls of the arteries. However, there’s some debate among medical professionals about the risk of ASCVD when the levels of other fats are normal. The American Heart Association suggests that individuals having FHTG may be at higher risk for ASCVD due to the presence of metabolic syndrome, a condition often connected with insulin resistance, hypertension, and central obesity.

The first step when managing FHTG is lifestyle modification. Consuming a low-fat diet, reducing simple carbohydrates and sugars, and avoiding alcohol can be beneficial for patients. A diet focusing on monounsaturated and polyunsaturated fats rather than saturated fats may improve the overall fat levels in the body. Fish or fish oil supplements with omega-3 fatty acids may also help in reducing fats and fat particles in the body. Your diet should contain a significant amount of fiber, found in foods like whole grains, legumes, fruits, and vegetables. Physicians recommend regular, moderate, and high-intensity exercises to improve your overall health and wellbeing.

If the lifestyle changes are unable to lower the fat levels adequately, doctors may consider prescribing medications according to the American College of Cardiology (ACC) and American Heart Association (AHA) guidelines. The different treatments depend on whether the patient has severe or mild-to-moderate hypertriglyceridemia (High levels of fat particles in the body).

For individuals with severe hypertriglyceridemia (fat particle levels of 500mg/dL or more), Fibrates, a class of medication, can be introduced. Fibrates work in numerous ways to alter fat metabolism, leading to a significant reduction in fat levels. Fenofibrate is often preferred over gemfibrozil because it has a lower risk of causing severe muscular disease when combined with other cholesterol-lowering medications. Omega-3 fish oil is also recommended to help lower the levels of fat particles. Prescription forms of eicosapentaenoic acid(EPA), derived from fish oil, could be more effective in reducing fat levels than over-the-counter products.

Statins, another class of medication, are often prescribed along with fibrates for patients with severe hypertriglyceridemia, who also have a high risk of ASCVD. Statins reduce the levels of low-density lipoprotein (“bad” cholesterol) and can also lessen the risk of ASCVD.

For patients with mild-to-moderate hypertriglyceridemia (fat particle levels of 150-499mg/dL) and poorly controlled significant risk factors for ASCVD and a 10-year ASCVD risk (≥7.5%), statins can be a helpful course of treatment. All patients with FHTG should address lifestyle changes that could contribute to elevated fat levels such as weight loss, quitting smoking, regular aerobic exercise, and a diet low in simple carbohydrates and sugars.

While newer experimental treatments are being researched, it is essential to be aware that the Food and Drug Administration (FDA) has fast-tracked “Olezarsen,” a new treatment administered via monthly injections for managing FHTG. This treatment is showing great promises and is currently under investigation for its long-term safety and effectiveness. To sum up, physicians often recommend medication to individuals with FHTG whose fat levels exceed 500 mg/dL to prevent acute pancreatitis or to those who are at risk for ASCVD. Treatments such as fibrates, omega-3 fatty acids, and statins are the primary medications recommended by the ACC and AHA.

What else can Familial Hypertriglyceridemia be?

: Doctors checking for FHTG, a condition that results in high levels of fat in the blood, need to make sure they exclude other conditions that also cause high fat levels. These other conditions could be the real cause of the high fat levels and include issues like uncontrolled diabetes, obesity, an underactive thyroid, kidney disease, heavy alcohol use, and the effects of certain medications.

The conditions that need to be ruled out include the following:

• Uncontrolled diabetes
• Obesity
• Underactive thyroid (hypothyroidism)
• Kidney disease
• Heavy alcohol use
• Effects of certain medications like corticosteroids, beta-blockers, estrogens, and antiretroviral therapy
• Genetic fat disorders like Familial Combined Hyperlipidemia (FCHL) and Type III Hyperlipoproteinemia

Doctors can differentiate FHTG from these other causes through various laboratory tests. These tests include fasting lipid panels, liver, kidney, and thyroid function tests, as well as some specific genetic tests. These tests help doctors to identify and rule out other reasons for high fat levels in the blood. A proper diagnosis depends on a careful review of the patient’s medical history, a physical examination, and these specific lab tests.

What to expect with Familial Hypertriglyceridemia

The outlook for individuals with Familial Hypertriglyceridemia (FHTG), an inherited condition that increases the levels of a specific fat called triglycerides in the blood, is generally positive. It usually doesn’t lead to an early onset of atherosclerotic cardiovascular disease (ASCVD), which is a heart condition caused by a buildup of plaque in the arteries, as long as their overall cholesterol levels are within a healthy range.

However, individuals with FHTG do have a higher risk of developing acute pancreatitis, which is a sudden inflammation of the pancreas, and chylomicronemia syndrome, which involves an excessive amount of certain fat particles in the blood. This is especially the case when there are other factors that worsen their high triglyceride levels.

Treatment for FHTG centers around lifestyle changes and medication, with the goal of lowering triglyceride levels in order to prevent complications from developing. With effective management, patients with this chronic condition can expect to lead a healthy life.

Possible Complications When Diagnosed with Familial Hypertriglyceridemia

FHTG, a condition related to high blood fats, and its treatments can lead to a variety of complications, including inflammation of the pancreas, skin nodules, changes in the retina, an elevated chance of heart and blood vessel disease, and gallstones. The risk of inflammation of the pancreas is directly linked to the level of blood fats, specifically when they are more than 500 mg/dL. This risk approximates 5% for levels over 1000 mg/dL and doubles to 10% when levels are above 2000 mg/dL. Also, the risk of such inflammation is greater in those who had a similar condition in the prior year. To manage it, treatment measures include intravenous fluids, pain control, insulin, and blood treatment option to lower blood fat levels.

Although people with FHTG typically have a minor increase in heart and blood vessel disease risk compared to FCHL patients, some research indicates high baseline blood fat levels could increase heart disease-related death in patients and their families. This suggests that having high blood fat levels could alone considerably raise heart disease risk. Complications of FHTG are avoided and managed through habit changes, drugs that lower blood fat levels, regular check-ups, managing existing health conditions, and immediate treatment of high blood fat levels to ensure the best possible health outcomes for patients.

Common Complications and Options for Treatment:

• Pancreas inflammation
• Skin nodules
• Retinal changes
• Elevated heart and blood vessel disease risk
• Gallstones
• Treatment options: IV fluids, pain control, insulin, lowering blood fat levels

Preventing Familial Hypertriglyceridemia

Educating patients about familial FHTG, a condition inherited from family members, is key to managing it effectively and avoiding complications. Familial FHTG causes high levels of triglycerides (a type of fat) in the blood. This puts you at a higher risk for acute pancreatitis, an inflammation of the pancreas, and ASCVD, which is a disease that causes blockages in the heart and blood vessels.

Living a healthy lifestyle will be particularly critical for patients with FHTG. This will include regular exercise, maintaining a healthy weight, and following a heart-healthy diet. You should avoid foods high in saturated fats and sugars to help control your triglyceride levels.

Your doctor will instruct you to take your prescribed medicine regularly. This helps in controlling the fat levels in your blood and in reducing the possibility of further health complications. Regular check-ups and specific blood tests while fasting will be necessary to track your progress.

Your doctor will also explain the genetic aspect of FHTG to you. This means understanding how the condition can affect other family members who might also need to be tested. Furthermore, patients must comprehend the importance of managing other conditions such as diabetes and obesity, which can make high triglyceride levels worse.

Providing those with FHTG with useful information and practical strategies will empower them. This will allow patients to manage their condition more effectively, which will enhance their overall health and quality of life.