What is Lipoprotein Lipase Deficiency?
Lipoprotein lipase deficiency is a genetic condition that a person inherits from their parents. This disorder typically starts in childhood and is marked by high levels of triglycerides – a type of fat in your blood, and chylomicrons – a type of lipoprotein. In simple terms, people with this condition have too much fat in their blood. It is the most common form of chylomicronemia, a condition where your blood has too many chylomicrons. This disorder used to be called hyperlipoproteinemia type 1a. The first people to describe this condition were Dr. Burger and Dr. Grutz in 1932.
What Causes Lipoprotein Lipase Deficiency?
Lipoprotein lipase deficiency is a condition that occurs when there’s a faulty gene responsible for producing a specific enzyme called lipoprotein lipase. The defects in this gene can result in either a decrease in the effectiveness of this enzyme or it may even cease all enzyme activity. These defects or mutations in the gene might happen in various ways, resulting in an abnormal lipoprotein lipase gene. There have been more than 220 different types of these faulty gene variants discovered, and these faults can range from changes in a single DNA base to deletions or insertions of several bases.
The way that lipoprotein lipase deficiency is passed down in families follows an autosomal recessive pattern. This means that both parents must have a copy of the faulty gene for a child to develop the disease. If both parents carry one copy of the defective gene, the chance their child will have lipoprotein lipase deficiency is 25% for each pregnancy. The child has a 50% chance of being a carrier of the gene (meaning they will not develop the disease but can pass the gene onto their offspring), and a 25% chance of not inheriting the gene at all. Similarly, each sibling of a person with lipoprotein lipase deficiency has a 25% chance of having the disease, a 50% chance of being a carrier, and a 25% chance of being unaffected.
Risk Factors and Frequency for Lipoprotein Lipase Deficiency
Lipoprotein lipase deficiency is a rare condition, affecting about 1 in every 1,000,000 people. Two specific gene mutations, G118E and P207L, found in Quebec, Canada, are known to cause this condition. If you have one of these mutations, it can lead to a complete loss of lipoprotein lipase activity if you have two copies of the mutation, or a 50% loss if you only have one copy.
This condition is typically found in children, usually before they turn ten years old, and in fact, about a quarter of patients are diagnosed in their first year of life. However, it can sometimes go unnoticed until adulthood. For instance, women might not show symptoms until they become pregnant. It’s also worth noting that this disorder affects both men and women equally.
- Lipoprotein lipase deficiency is a rare disease affecting about 1 in 1 million people.
- In Quebec, Canada, two specific mutations (G118E and P207L) have been discovered that cause this condition.
- People with these mutations can experience a total or partial loss of lipoprotein lipase activity.
- Most patients are diagnosed as children, usually before the age of 10.
- About 25% of patients are identified in their first year of life.
- Some people, especially women, might not show symptoms until adulthood.
- Both males and females are affected by this condition equally.
Signs and Symptoms of Lipoprotein Lipase Deficiency
Lipoprotein lipase deficiency is a medical condition that can cause a variety of symptoms. Here are some of them:
- Most people with this condition experience abdominal pain, which can vary from mild to severe. This is due to acute pancreatitis, an inflammation of the pancreas. This pain can happen over and over and may lead to long-term pancreatitis.
- People with this condition often develop xanthomas. These are yellow, 1 mm bumps that typically appear on the torso, knees, buttocks, and the outer parts of the arms. They happen when the levels of triglycerides (a type of fat) in the blood are above 2000 mg/dL. When the triglyceride levels return to normal, these bumps usually disappear.
- The liver and spleen can become enlarged due to extremely high levels of triglycerides in the blood. The excessive chylomicrons (a type of fat) in the bloodstream are consumed by macrophages (a type of immune cell), which then travel to the liver and spleen. Fatty cells build up in these organs, leading to their enlargement.
- There can be changes to the retina in the eye called retinalis lipemia. This makes the vessels of the retina appear pinkish due to the scattering of light by large chylomicrons. Vision generally remains normal, and these changes are reversible once triglyceride levels go down.
- Cognitive changes like mild mental dysfunction, depression, and memory loss may occur. These changes can also be reversed.
- Infants with this condition can experience additional symptoms like abdominal pain (which can appear as colic), irritability, diarrhea, intestinal bleeding, paleness, seizures, and failure to thrive.
- Women with lipoprotein lipase deficiency may not experience symptoms until they become pregnant. This is due to the body absorbing more triglyceride-rich lipoproteins during pregnancy.
The severity of these symptoms is linked to the levels of chylomicrons in the body.
Testing for Lipoprotein Lipase Deficiency
Lipoprotein lipase deficiency is a condition that some young individuals, who are experiencing specific patterns of health issues along with some supportive lab results, might have.
Health Issues
1. Regular bouts of severe pancreatitis, which is an inflammation of the pancreas.
2. Eruptive xanthoma, which are bumpy and red skin patches.
3. Hepatosplenomegaly, or enlargement of both the liver and the spleen.
4. Retinalis lipemia, a disorder that affects the eyes.
Lab Signs
1. Blood plasma samples that appear milky. This may indicate an inability to clear a certain type of fat particles, called chylomicrons, from the blood.
2. Blood plasma triglyceride levels, a type of fat in the blood, that exceed 2000 mg/dL. These readings are taken into account regardless of whether the person has eaten recently or not.
Diagnosis
This condition is properly diagnosed via genetic testing that spots certain harmful changes, known scientifically as biallelic pathogenic variants, in the gene that produces lipoprotein lipase. Two types of tests are used:
* Sequence analysis, which finds these harmful genetic changes in 97% cases.
* Gene targeted duplication/deletion analysis, which uncovers these harmful genetic changes in about 4% of cases.
Some people may undergo genetic testing that focuses solely on detecting any harmful changes in the lipoprotein lipase gene. In other cases, doctors may opt to run a broader genetic panel that also checks for harmful changes in four other genes that can cause similar symptoms.
Another method for diagnosis involves measuring lipoprotein lipase activity. This is done via plasma testing – doctors inject the patient with a substance called heparin and measure how many fat cells are released. This measurement is provided as the concentration of fat cells per minute per liter of plasma. If harmful genetic changes are present in the lipoprotein lipase enzyme or its helper protein, called apolipoprotein C-II, the test may show no detectable activity, which is a sign of familial lipoprotein lipase deficiency.
In some cases, doctors may also take small tissue samples, also known as biopsies, from the fat tissue to measure the lipoprotein lipase directly.
Treatment Options for Lipoprotein Lipase Deficiency
When someone is diagnosed with a condition called lipoprotein lipase deficiency, doctors usually recommend a diet that limits fat intake. This is intended to reduce the levels of a kind of fat called triglycerides in the blood to avoid symptoms. The goal is to lower these triglyceride levels to below 2000 mg/dL, though the best results come from achieving levels below 1000 mg/dL. These levels can be achieved by keeping daily fat intake below 20 grams, or below 15% of total calorie intake.
Contrary to what you might expect, fish oil supplements aren’t helpful for people with this condition, and shouldn’t be used. That’s because fish oils contribute to something called chylomicrons, which the body has a hard time processing when it has a lipoprotein lipase deficiency. Certain other substances that can increase the amount of triglycerides in the blood, like alcohol, estrogen birth control pills, certain medications for blood pressure (beta-adrenergic blockers), medications for mental health (selective serotonin reuptake inhibitors), and isotretinoin should be avoided.
Due to a severely low-fat diet, supplementation of fat-soluble vitamins like A, D, E, K, along with minerals, is advised.
If a person with lipoprotein lipase deficiency gets pancreatitis, an inflammation of the pancreas, it’s treated the same way as pancreatitis caused by other things. Proper diet management would prevent recurrent pancreatitis and reduce the risk of pancreatitis-related complications like diabetes.
The doctor will keep an eye on the patient’s triglyceride levels over time to see if the diet is working.
If a woman with lipoprotein lipase deficiency becomes pregnant, she’ll need to follow an even stricter low-fat diet during her pregnancy, especially in the second and third trimesters. With a low-fat diet and monitoring of her triglyceride levels, she can have a normal pregnancy.
For people in their childbearing years, genetic counseling may be offered to discuss the genetic risks and implications of this condition.
There was a gene therapy called alipogene tiparvovec, which used a genetically edited virus to mark the lipoprotein lipase gene in muscle cells, in turn, reducing the levels of triglycerides. Though this treatment significantly helped people with the most severe risks, it is no longer available due to low demand.
Current budding treatments include Pradigastat, an oral medication that interferes with the last step of triglyceride creation and reduces the secretion of chylomicron-triglycerides, and Evinacumab, a lab-made antibody that inhibits lipoprotein lipase.
What else can Lipoprotein Lipase Deficiency be?
If a young person has severely high triglyceride levels, more specifically over 2000 mg/dl, they might have LPL deficiency, a condition tied to high levels of a type of fat called chylomicronemia. However, research shows that this isn’t always the case, as they could instead have a more common genetic disorder that affects fat metabolism like familial combined hyperlipidemia or monogenic familial hypertriglyceridemia. It’s also possible that other factors are causing the high triglyceride levels.
While LPL deficiency is often the main source of primary monogenic chylomicronemia variants, making up about 95% of these cases, there are other conditions that could be the cause:
- Familial apolipoprotein C- II deficiency. This leads to severe chylomicronemia in children or teenagers, accounting for 2% of these variants.
- Familial apolipoprotein A-V deficiency. This can cause chylomicronemia in adults late in life and it accounts for 0.6% of these variants.
- Familial lipase maturation factor 1 deficiency. This could also trigger chylomicronemia in adults late in life and it represents about 0.4% of these variants.
- Familial glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 deficiency. This can cause chylomicronemia in adults late in life and it accounts for 2.0% of these variants.
Outside of these genetic conditions, there are other underlying reasons that can lead to high triglyceride levels, including:
- Diabetes
- Paraproteinemia and lymphoproliferative disorders (certain blood conditions)
- Alcohol use
- Estrogen therapy
- Certain medications like selective serotonin receptor reuptake inhibitors, glucocorticoids, some unconventional antipsychotics, isotretinoin, and some types of blood pressure medications.
What to expect with Lipoprotein Lipase Deficiency
The main line of treatment for lipoprotein lipase deficiency is through dietary changes, specifically a low-fat diet. What this means is that patient’s success in managing this deficiency heavily depends on how well they can stick to this diet. If a patient can consistently follow a low-fat diet, they can expect a good outcome because it helps to lower the levels of triglycerides (a type of fat) in their blood.
Additionally, typical side effects of this deficiency such as an enlarged liver and spleen usually go back to their normal size within a week of lowering triglyceride levels. Skin blemishes or bumps that occur due to fat build-up in the skin, called eruptive xanthomas, also clear up within a few weeks to months.
Even if a person with lipoprotein lipase deficiency has had multiple instances of acute pancreatitis (a serious inflammation of the pancreas), the decline in pancreatic function is slow. This means it’s usually not associated with a high risk of death.
Possible Complications When Diagnosed with Lipoprotein Lipase Deficiency
People with lipoprotein lipase deficiency can experience recurring severe inflammation of the pancreas, which can eventually turn into chronic inflammation. This, in turn, can potentially lead to secondary complications like:
- Diabetes mellitus
- Steatorrhea – a condition where stools contain excess fat due to an inability to properly absorb fat
- Pancreatic calcifications
However, these complications are not common in people with lipoprotein lipase deficiency. They usually only occur in the later stages of life, if they occur at all. It’s also important to note that serious complications, like complete damage to the pancreas or even death, are extremely rare but could occur due to pancreatitis.
Preventing Lipoprotein Lipase Deficiency
People with lipoprotein lipase deficiency often face a reduced quality of life. This is mainly due to frequently experiencing pancreatitis, which is a painful condition caused by inflammation of the pancreas. The constant bouts of pancreatitis can lead to them feeling anxious, depressed, and frustrated, especially during and after hospital stays. Frequent hospital visits can disrupt their daily life activities, like work, due to being absent often. This can also lead to financial concerns and increased reliance on family and friends for support.
To help lower the consequences of this condition, it’s vitally important for patients to follow a diet with low levels of fat. This can help reduce the signs and symptoms of lipoprotein lipase deficiency and prevent related health problems from arising. Changes in their everyday life, such as cooking with medium-chain fatty acids, which are a type of fat that is directly absorbed into the blood without further breakdown, can help with this. Consulting a dietitian may also be beneficial in managing daily fat intake. Regular check-ups to assess the patient’s diet and triglyceride (a type of fat found in the blood) levels are useful in ensuring the effectiveness of the dietary approach.
In addition to dietary measures, genetic counseling is highly beneficial. In genetic counseling, the patient is educated about the nature of their condition, how it is inherited, and what impacts it might have on their lives. Understanding their condition better can help them make well-informed decisions about their health. Moreover, early diagnosis of the condition and adopting necessary dietary modifications can help prevent the onset of symptoms and complications.