familial apolipoprotein C-II deficiency

Familial apolipoprotein C-II deficiency, also known as Familial chylomicronemia syndrome, is a rare genetic disorder characterized by the inability to properly break down fats in the body.

Key Features:

• Increased plasma levels of triglycerides and chylomicrons: The condition leads to an accumulation of these lipids in the bloodstream, causing various symptoms.
• Abnormality of metabolism/homeostasis: The deficiency affects the normal metabolic process, leading to an imbalance in lipid metabolism.
• Decreased circulating apolipoprotein C-II concentration: ApoC-II plays a crucial role in the breakdown of fats; its deficiency leads to impaired lipoprotein lipase activity.

Clinical Features:

• Hepatomegaly (enlarged liver)
• Pancreatitis (inflammation of the pancreas)
• Splenomegaly (enlarged spleen)
• Skin eruptions

Inheritance Pattern:

• Autosomal recessive disorder: The condition is inherited in an autosomal recessive manner, meaning that a person must inherit two copies of the mutated gene (one from each parent) to express the condition.

Similar Conditions:

• Lipoprotein lipase deficiency: This rare condition also affects the breakdown of fats and can present with similar symptoms.
• ApoC-II levels are also seen in people with low ApoC-II levels: Individuals with this condition may have decreased apoC-II levels, which can be a contributing factor to their symptoms.

References:

• [6] Familial apolipoprotein CII deficiency is a very rare (rarer than LPL deficiency) autosomal recessive disorder in which apolipoprotein CII (apoC-II), a ...
• [7] An inborn error of metabolism characterized by increased plasma levels of triglycerides and chylomicrons.
• [8] This is a condition in which the body does not break down fats normally. Low ApoCII levels are also seen in people with a rare genetic disorder called Familial apolipoprotein C-II deficiency.
• [9] The condition leads to an accumulation of triglycerides and chylomicrons in the bloodstream, causing various symptoms.

Note: The references provided are based on the information within the context section.

Familial apolipoprotein C-II deficiency is a rare autosomal recessive disorder characterized by several signs and symptoms, which can vary in severity and age of onset.

Common Signs and Symptoms:

• Hepatomegaly (enlarged liver)
• Pancreatitis (inflammation of the pancreas)
• Splenomegaly (enlarged spleen)
• Skin eruptions
• High triglyceride levels in the blood

These symptoms are often associated with familial lipoprotein lipase deficiency, and the two conditions are clinically and biochemically similar. However, there are some differences in the age of

Familial apolipoprotein C-II deficiency can be diagnosed through various tests that measure the activity and structure of the lipoprotein lipase enzyme.

• Low or absent enzyme activity: Diagnosis is based on low or absent enzyme activity in an assay system that excludes other lipolytic enzymes and contains normal plasma or apoprotein C-II, a necessary cofactor of the enzyme [1].
• Genetic testing: Diagnosis can also be confirmed by demonstration of a defect in the structure of the lipoprotein lipase gene through genetic testing, such as sequence analysis of the entire coding region [3].
• Clinical Molecular Genetics test: A Clinical Molecular Genetics test for Familial apolipoprotein C-II deficiency is available, which includes sequence analysis of the entire coding region and bi-directional Sanger Sequence Analysis offered by Asper Biogene [4].

These diagnostic tests can help identify individuals with familial apolipoprotein C-II deficiency, a rare genetic disorder that affects the metabolism of lipids in the body.

References:

[1] Context 1: Familial apolipoprotein C-II deficiency is characterized by hepatomegaly, pancreatitis, splenomegaly, and skin eruptions. ... Diagnosis is based on low or absent enzyme activity in an assay system that excludes other lipolytic enzymes and contains normal plasma or apoprotein C-II, a necessary cofactor of the enzyme;

[3] Context

Current Treatment Options

Familial apolipoprotein C-II deficiency, a rare autosomal recessive disorder, has limited treatment options available. The condition is characterized by hepatomegaly, pancreatitis, splenomegaly, and skin eruptions, with patients often developing chronic pancreatic insufficiency and steatorrhea.

• Lipid-lowering drugs are not effective: Unlike other disorders of lipid metabolism, the lipid-lowering drugs used to treat conditions such as familial lipase maturation factor 1 (LMF1) deficiency or familial apolipoprotein C-II deficiency do not provide relief for individuals with familial apolipoprotein C-II deficiency. [1][2]
• LPL gene therapy: In contrast, LPL gene therapy is available in Europe and the US for the treatment of familial lipase maturation factor 1 (LMF1) deficiency, which shares similarities with familial apolipoprotein C-II deficiency. However, this treatment option may not be directly applicable to individuals with familial apolipoprotein C-II deficiency. [3]
• Orlistat: Orlistat, a medication used for the treatment of type I hyperlipoproteinemia, has been investigated as a potential treatment for familial apolipoprotein C-II deficiency. However, its effectiveness in this condition is unclear. [4]

Emerging Research and Treatment Directions

Recent studies have explored new avenues for treating familial apolipoprotein C-II deficiency. For instance:

• APOC3 inhibitors: APOC3 inhibitors, such as those targeting the APOC3 gene, have shown promise in reducing triglyceride levels in individuals with familial lipoprotein lipase deficiency and apo CII deficiency. [5]
• Gene therapy: Gene therapy approaches are being investigated for the treatment of familial apolipoprotein C-II deficiency, aiming to correct the underlying genetic defect responsible for the condition.

Conclusion

While there is no established effective treatment for familial apolipoprotein C-II deficiency, ongoing research and emerging therapeutic options offer hope for improved management of this rare disorder. Further studies are needed to determine the efficacy and safety of these potential treatments.

Familial apolipoprotein C-II deficiency has several differential diagnoses, which are conditions that can present with similar symptoms and characteristics. Some of the key differential diagnoses include:

• Lipoprotein lipase (LPL) deficiency: This condition is characterized by severe hypertriglyceridemia and chylomicronemia, similar to familial apolipoprotein C-II deficiency. In fact, the two conditions are often clinically and biochemically indistinguishable [1][2].
• Familial combined hyperlipidemia (FCHL): This is a genetic disorder that affects lipid metabolism, leading to elevated levels of triglycerides, cholesterol, and other lipids in the blood. While FCHL can present with similar symptoms to familial apolipoprotein C-II deficiency, it typically involves a broader range of lipid abnormalities [3].
• Familial hypercholesterolemia (FH): This is another genetic disorder that affects lipid metabolism, leading to elevated levels of LDL cholesterol in the blood. While FH can present with similar symptoms to familial apolipoprotein C-II deficiency, it typically involves a more pronounced elevation of LDL cholesterol [4].
• Gall stones and pancreatitis: These conditions can also present with similar symptoms to familial apolipoprotein C-II deficiency, including abdominal pain and elevated levels of triglycerides in the blood [5].

It's worth noting that differential diagnoses for familial apolipoprotein C-II deficiency are typically considered based on a combination of clinical presentation, laboratory results, and family history. A thorough evaluation by a qualified healthcare professional is necessary to accurately diagnose this condition.

References:

[1] Regmi M (2023) - Differential Diagnosis [2] Balasubramanian S (2020) - Differential Diagnosis [3] Susheela AT (2021) - Differential diagnosis included familial hypercholesterolemia, familial triglyceredemia, and familial combined hyperlipidemia. [4] Falko JM (2018) - Patients with FCS can be identified based on a defined clinical criteria and a thorough review of medical history, after excluding differential diagnoses and [5] Susheela AT (2021) - Differential diagnosis included gall stones and pancreatitis