What is Apolipoprotein B (Apo B) deficiency?

From the Guidelines

ApoB deficiency is a rare genetic disorder characterized by the inability to produce sufficient amounts of ApoB protein, leading to extremely low levels of cholesterol and triglycerides in the blood, and is associated with conditions such as abetalipoproteinemia and familial hypobetalipoproteinemia, as described in a 2021 study published in the European Heart Journal 1. This condition prevents the normal formation of lipoproteins that carry fats and fat-soluble vitamins throughout the body, resulting in symptoms such as fat malabsorption, diarrhea, failure to thrive in infants, progressive vision problems, and neurological issues due to vitamin E deficiency. Some key points to consider about ApoB deficiency include:

• Abetalipoproteinemia is characterized by the absence of serum apoB-containing lipoproteins, undetectable LDL-C, and deficiency of lipid soluble vitamins (A, D, E, K) 1.
• Familial hypobetalipoproteinemia (FHBL) is an autosomal dominant disorder caused by mutations of the apoB gene, resulting in decreased lipidation and secretion of apoB-containing lipoproteins 1.
• Treatment focuses on dietary management with a low-fat diet and supplementation with fat-soluble vitamins (A, D, E, and K), particularly high-dose vitamin E to prevent neurological complications, as supported by the 2021 study 1.
• Regular monitoring of vitamin levels and neurological function is essential, as untreated ApoB deficiency can lead to serious complications including retinal degeneration, muscle weakness, and nerve damage. The most effective treatment approach for ApoB deficiency is lifelong supplementation with high-dose vitamin E, which appears to halt further neurological degeneration, as reported in the 2021 European Heart Journal study 1.

From the Research

Apo B Deficiency

Apo B deficiency refers to a condition where there is a lack or low levels of apolipoprotein B (apo B) in the body. Apo B is a critical protein component of low-density lipoprotein (LDL) cholesterol and is essential for the transport and metabolism of lipids in the body.

Causes of Apo B Deficiency

• Abetalipoproteinemia (ABL) is a rare autosomal recessive disorder caused by biallelic pathogenic mutations in the MTTP gene, leading to a deficiency of microsomal triglyceride transfer protein (MTTP) and impaired assembly of apo B-containing lipoproteins 2.
• Familial hypobetalipoproteinemia is caused by mutations in the apo B gene, resulting in abnormally low plasma concentrations of apo B and LDL cholesterol 3, 4.
• Other apo B deficiency syndromes, such as Anderson's disease, are characterized by the inability to secrete apo B-containing chylomicrons from the intestine 4.

Clinical Manifestations

• Patients with ABL typically manifest steatorrhea, vomiting, and failure to thrive in infancy, with progressive development of hematological, neuromuscular, and ophthalmological symptoms later in life 2.
• Familial hypobetalipoproteinemia heterozygotes are often asymptomatic, while homozygotes and compound heterozygotes may experience severe problems related to intestinal fat malabsorption 3.
• Apo B deficiency has been associated with an increased risk of liver disease, including fatty liver, cirrhosis, and hepatocellular carcinoma 5.

Diagnosis and Management

• Diagnosis of apo B deficiency syndromes often involves genetic testing and measurement of plasma apo B and LDL cholesterol levels 2, 3.
• Management of apo B deficiency syndromes typically involves high-dose vitamin supplementation and other supportive therapies to prevent or alleviate complications 2.
• Novel therapeutic modalities, such as PCSK9 inhibitors, may also be effective in reducing cardiovascular risk in individuals with apo B deficiency 6, 5.