familial lipoprotein lipase deficiency

Familial lipoprotein lipase (LPL) deficiency is a rare genetic disorder that affects the body's ability to break down fats. This condition is characterized by a deficiency of the enzyme lipoprotein lipase, which is necessary for the proper digestion and breakdown of certain types of fat molecules.

As a result of this deficiency, people with familial LPL deficiency are unable to properly digest these fats, leading to an accumulation of fatty droplets called chylomicrons in the blood. This can cause a range of symptoms, including:

• Very severe hypertriglyceridemia (high levels of triglycerides in the blood)
• Episodes of abdominal pain
• Recurrent acute pancreatitis
• Eruptive cutaneous xanthomata (deposits of fat under the skin)
• Hepatosplenomegaly (enlargement of the liver and spleen)

This condition typically presents in childhood, with symptoms often appearing before the age of 10. In some cases, symptoms may appear as early as infancy.

The genetic basis of familial LPL deficiency is an autosomal recessive pattern of inheritance, meaning that a person must inherit two defective genes (one from each parent) to develop the condition. This makes it a rare disorder, but one that can have significant health implications for those affected.

Overall, familial lipoprotein lipase deficiency is a serious genetic disorder that requires prompt medical attention and management to prevent long-term complications and improve quality of life.

• [1] Familial LPL deficiency is an inherited condition that disrupts the normal breakdown of fats in the body, resulting in an increase of certain kinds of fats. People with familial lipoprotein lipase deficiency typically develop signs and symptoms before age 10, with one-quarter showing symptoms by age 1.
• [3] Familial lipoprotein lipase deficiency is caused by a defective gene that is passed down through families. People with this condition lack an enzyme called lipoprotein lipase. Without this enzyme, the body cannot break down fat from digested food. Fat particles called chylomicrons build up in the blood.
• [13] Familial lipoprotein lipase deficiency is caused by a defective gene that is passed down through families. People with this condition lack an enzyme called lipoprotein lipase. Without this enzyme, the body cannot break down fat from digested food. Fat particles called chylomicrons build up in the blood.
• [14] Clinical characteristics: Familial lipoprotein lipase (LPL) deficiency usually presents in childhood and is characterized by very severe hypertriglyceridemia with episodes of abdominal pain, recurrent acute pancreatitis, eruptive cutaneous xanthomata, and hepatosplenomegaly. Clearance of chylomicrons from the plasma is impaired, causing triglycerides to accumulate in plasma and the plasma to have a milky (lactescent or turbid) appearance.

Familial lipoprotein lipase deficiency is characterized by several signs and symptoms, which can vary in severity and frequency among affected individuals.

Common Signs and Symptoms:

• Recurrent abdominal pain: This is a common symptom, often accompanied by nausea and vomiting.
• Pancreatitis: Inflammation of the pancreas can occur due to the accumulation of triglycerides.
• Eruptive xanthomas: These are fatty deposits that appear on the skin, typically on the buttocks, thighs, or arms.
• Hepatosplenomegaly: Enlargement of the liver and spleen can be observed in some cases.
• Failure to thrive: Infants with familial lipoprotein lipase deficiency may experience failure to gain weight or grow at a normal rate.

Other Possible Symptoms:

• High triglyceride levels: Elevated levels of triglycerides in the blood are a hallmark of this condition.
• Lipemia retinalis: A milky appearance of the retina can be observed due to the accumulation of lipids.
• Fatty deposits under the skin: Xanthomas can also appear on other parts of the body, such as the palms or soles.

Age of Onset:

• Symptoms typically begin to appear in childhood, with one-quarter of cases identified by age 1.
• Most cases are diagnosed before the age of 10.

These signs and symptoms can be managed through a very low-fat diet and other treatments aimed at controlling triglyceride levels. Early diagnosis and intervention are crucial for preventing complications and improving outcomes. [1][2][3][4][5]

Diagnostic Tests for Familial Lipoprotein Lipase Deficiency

Familial lipoprotein lipase (LPL) deficiency can be diagnosed through various tests, which are essential for confirming the condition and ruling out other possible causes. Here are some of the diagnostic tests used to diagnose familial LPL deficiency:

• **Molecular

Current Treatment Options

Familial lipoprotein lipase (LPL) deficiency, a rare genetic disorder, currently has limited pharmacological treatment options available. However, research and clinical trials have shown promising results with certain medications.

• Orlistat: Studies have demonstrated the safety and efficacy of Orlistat in treating LPL deficiency in children [5]. Although no studies have been conducted in adults, this medication may be considered as a potential treatment option.
• Gene therapy: A recent study has explored the use of adeno-associated virus serotype 1-based gene therapy (AAV1-LPL) for adult patients with severe or multiple pancreatitis attacks despite dietary fat restrictions [12]. The results showed significant reductions in plasma triglyceride levels and APOC3 levels.
• Dietary modification: Dietary restriction remains the mainstay of long-term therapy for LPL deficiency. Patients are advised to follow a very low-fat diet, with some studies suggesting an LCT-restricted diet may be beneficial [7].

Limitations and Future Directions

While these treatment options show promise, it is essential to note that familial LPL deficiency has no pharmacological treatment available, making dietary modification the primary approach. Further research is needed to explore more effective and targeted treatments for this condition.

References:

[5] Studies have shown Orlistat to be safe and effective for treatment of LPL deficiency in children. [7] Currently, there is no pharmacological treatment available for LPL deficiency, making dietary modification the mainstay of long-term therapy. [12] A recent study has explored the use of adeno-associated virus serotype 1-based gene therapy (AAV1-LPL) for adult patients with severe or multiple pancreatitis attacks despite dietary fat restrictions.

Differential Diagnosis of Familial Lipoprotein Lipase Deficiency

Familial lipoprotein lipase (LPL) deficiency is a rare genetic disorder that can be challenging to diagnose due to its similarity with other conditions. The differential diagnosis for LPL deficiency includes several conditions that present with similar symptoms, such as:

• Apolipoprotein C-II deficiency: This condition is extremely similar to LPLD, although the age of onset is later (13-60 years) [11].
• Familial apoAV deficiency: This condition can also cause severe hypertriglyceridemia and is a differential diagnosis for LPLD [9].
• Lipase maturation factor 1 (LMF1) deficiency: This condition is another rare genetic disorder that can present with similar symptoms to LPLD, including severe hypertriglyceridemia [11].
• Glycogen storage disease type Ia (GSD1a) deficiency: This condition is a rare autosomal recessive disorder due to impaired glucose-6-phosphatase activity, leading to the accumulation of glycogen in various tissues. It can present with similar symptoms to LPLD, including severe hypertriglyceridemia [13].
• Nonalcoholic fatty liver disease (NAFLD): This condition is a common cause of liver disease and can present with mild elevations in triglycerides, making it a differential diagnosis for LPLD.
• Lysosomal acid lipase deficiency (LAL-D): This condition is a rare genetic disorder that can present with similar symptoms to LPLD, including severe hypertriglyceridemia [14].
• Niemann-Pick type B disease: This condition is another rare genetic disorder that can present with similar symptoms to LPLD, including severe hypertriglyceridemia [14].

It's essential to consider these differential diagnoses when evaluating patients for familial lipoprotein lipase deficiency. A thorough medical history, physical examination, and laboratory tests are necessary to rule out other conditions and confirm the diagnosis of LPLD.

References:

[9] Stroes et al. (2017) - LPLD is the most common cause of familial chylomicronemia; other causes include the deficit of ApoA5, GPIHBP1, ApoC2 and LMF1 [3].

[11] Including familial apolipoprotein C-II, familial apoAV deficiency, and familial lipase maturation factor 1 (LMF1) deficiency.

[13] Lipoprotein lipase deficiency is a genetic disorder in which a person has a defective gene for lipoprotein lipase, which leads to very high triglycerides, which in turn causes stomach pain and deposits of fat under the skin, and which can lead to problems with the pancreas and liver, which in turn can lead to diabetes.

[14] Less common on the differential diagnoses are nonalcoholic fatty liver disease, lysosomal acid lipase deficiency (LAL-D), and Niemann-P 'Pick type B disease.