Summary about Disease
Lipoprotein Lipase Deficiency (LPLD), also known as familial chylomicronemia syndrome (FCS) or hyperlipoproteinemia type I, is a rare, inherited genetic disorder characterized by a deficiency or absence of lipoprotein lipase (LPL) enzyme activity. This enzyme is crucial for breaking down triglycerides in chylomicrons (fat particles from the diet) and very-low-density lipoproteins (VLDL) in the bloodstream. The deficiency leads to a severe buildup of triglycerides in the blood (hypertriglyceridemia).
Symptoms
Severe abdominal pain (often recurring)
Hepatosplenomegaly (enlarged liver and spleen)
Eruptive xanthomas (small, yellowish bumps on the skin)
Lipemia retinalis (milky appearance of retinal blood vessels)
Pancreatitis (inflammation of the pancreas) – a significant and potentially life-threatening complication
Fatigue
Failure to thrive (in infants)
Neurological symptoms (rare, but possible in severe cases)
Causes
LPLD is caused by mutations in the LPL gene. This gene provides instructions for making the lipoprotein lipase enzyme. The mutations result in a non-functional or deficient enzyme. It is inherited in an autosomal recessive manner, meaning that an individual must inherit two copies of the mutated gene (one from each parent) to develop the condition. If an individual inherits only one mutated gene, they are considered a carrier and usually do not exhibit symptoms, though they may have moderately elevated triglyceride levels.
Medicine Used
Gene Therapy (Glybera): Glybera was the first gene therapy approved for LPLD in Europe. It used an adeno-associated virus (AAV) vector to deliver a functional copy of the LPL* gene into muscle cells. However, it was withdrawn from the market due to limited use and high cost.
Volanesorsen (Waylivra): Volanesorsen is an antisense oligonucleotide that reduces the production of apolipoprotein C-III (apoC-III), a protein that inhibits LPL. It helps lower triglyceride levels.
Other Lipid-Lowering Agents: Fibrates and omega-3 fatty acids are sometimes used as adjunctive therapies, but their effectiveness in LPLD is limited due to the primary defect being a lack of LPL.
Is Communicable
No, Lipoprotein Lipase Deficiency is not communicable. It is a genetic disorder caused by inherited gene mutations and cannot be transmitted from person to person.
Precautions
Strict Dietary Fat Restriction: The most important precaution is a very low-fat diet (typically less than 20 grams of fat per day). This helps minimize the amount of chylomicrons produced after eating, reducing triglyceride levels.
Avoid Alcohol: Alcohol can significantly increase triglyceride levels and should be avoided.
Regular Monitoring: Regular blood tests to monitor triglyceride levels and liver function are essential.
Genetic Counseling: Genetic counseling is recommended for families affected by LPLD to understand the inheritance pattern and the risk of having affected children.
Pancreatitis Awareness: Be vigilant for symptoms of pancreatitis (severe abdominal pain, nausea, vomiting) and seek immediate medical attention if they occur.
How long does an outbreak last?
LPLD is a chronic condition. While individual episodes of symptoms like abdominal pain or eruptive xanthomas can resolve, the underlying deficiency persists throughout life. "Outbreaks" generally refer to acute episodes like pancreatitis or periods of uncontrolled hypertriglyceridemia, which can last days to weeks depending on the severity and treatment. The key is management to prevent such outbreaks.
How is it diagnosed?
Lipid Profile: Severely elevated triglyceride levels (typically >1000 mg/dL, often >2000 mg/dL) are a primary indicator.
Lipoprotein Lipase Activity Assay: This measures the activity of the LPL enzyme in a blood sample. Reduced or absent activity confirms the diagnosis.
Genetic Testing: Molecular genetic testing to identify mutations in the LPL gene can confirm the diagnosis, particularly in cases where LPL activity assays are unavailable or inconclusive.
Clinical Evaluation: Medical history, physical examination, and assessment of symptoms are crucial for considering the diagnosis.
Exclusion of Secondary Causes: Ruling out other conditions that can cause hypertriglyceridemia (e.g., diabetes, hypothyroidism, medications) is important.
Timeline of Symptoms
Infancy/Childhood: Symptoms often manifest in infancy or early childhood, including failure to thrive, abdominal pain, eruptive xanthomas, and lipemia retinalis.
Adolescence/Adulthood: While the condition is typically diagnosed early, some individuals may not be diagnosed until adolescence or adulthood, especially if symptoms are milder or misattributed to other causes. Episodes of pancreatitis can occur at any age.
Lifelong: The underlying LPL deficiency persists throughout life, requiring ongoing management to prevent complications.
Important Considerations
Differential Diagnosis: It's crucial to differentiate LPLD from other causes of hypertriglyceridemia, especially secondary causes and other genetic hyperlipidemias.
Pancreatitis Risk: The high risk of pancreatitis is a major concern, as it can lead to severe complications, including pancreatic necrosis, pseudocyst formation, and even death.
Dietary Adherence: Strict adherence to a very low-fat diet is essential for managing the condition.
Pregnancy: Pregnancy poses a significant risk for women with LPLD, as hormone changes can further elevate triglyceride levels, increasing the risk of pancreatitis.
Psychosocial Impact: The restrictive diet and chronic nature of the condition can have a significant psychosocial impact, requiring support for both the individual and their family.
Rare Disease Status: LPLD is a rare disease, and access to specialized care and support may be limited.
Research and Emerging Therapies: Research is ongoing to develop new and more effective therapies for LPLD, including gene therapies and other novel approaches.