Abetalipoproteinemia is an inherited disorder that impairs the normal absorption of fats and certain vitamins from the diet. Many of the signs and symptoms of abetalipoproteinemia result from a severe shortage (deficiency) of fat-soluble vitamins (vitamins A, E, and K). The signs and symptoms of this condition primarily affect the gastrointestinal system, eyes, nervous system, and blood.

The first signs and symptoms of abetalipoproteinemia appear in infancy. They often include failure to gain weight and grow at the expected rate (failure to thrive); diarrhea; and fatty, foul-smelling stools (steatorrhea).

As an individual with this condition ages, additional signs and symptoms include disturbances in nerve function that may lead to poor muscle coordination and difficulty with balance and movement (ataxia). They can also experience a loss of certain reflexes, impaired speech (dysarthria), tremors or other involuntary movements (motor tics), a loss of sensation in the extremities (peripheral neuropathy), or muscle weakness. The muscle problems can disrupt skeletal development, leading to an abnormally curved lower back (lordosis), a rounded upper back that also curves to the side (kyphoscoliosis), high-arched feet (pes cavus), or an inward- and upward-turning foot (clubfoot).

Individuals with this condition may also develop an eye disorder called retinitis pigmentosa, in which breakdown of the light-sensitive layer (retina) at the back of the eye can cause vision loss. In individuals with abetalipoproteinemia, the retinitis pigmentosa can result in complete vision loss. People with abetalipoproteinemia may also have other eye problems, including involuntary eye movements (nystagmus), eyes that do not look in the same direction (strabismus), and weakness of the external muscles of the eye (ophthalmoplegia).

Individuals with abetalipoproteinemia usually have a low number of red blood cells (anemia) with abnormally star-shaped red blood cells (acanthocytosis) and have difficulty forming blood clots, which can cause abnormal bleeding. In some cases, a condition called fatty liver develops, which can cause liver damage.

Abetalipoproteinemia is caused by mutations in the MTTP gene, which provides instructions for making a protein called microsomal triglyceride transfer protein. This protein is essential for creating molecules called beta-lipoproteins in the liver and intestine. Beta-lipoproteins transport fats, cholesterol, and fat-soluble vitamins from the intestine to the bloodstream so these nutrients can be taken up by tissues throughout the body. Sufficient levels of fats, cholesterol, and vitamins are necessary for normal growth, development, and maintenance of the body's cells and tissues.

Most MTTP gene mutations lead to the production of microsomal triglyceride transfer protein with reduced or absent function and unable to help in the formation of beta-lipoproteins. A lack of beta-lipoproteins causes severely reduced absorption (malabsorption) of dietary fats and fat-soluble vitamins from the digestive tract into the bloodstream. These nutritional deficiencies lead to health problems in people with abetalipoproteinemia.

Normal Function

The MTTP gene provides instructions for making a protein called microsomal triglyceride transfer protein. This protein helps produce beta-lipoproteins, which are molecules that are made up of proteins (including one called apolipoprotein B), cholesterol, and particular types of fats called phospholipids and triglycerides.

Different types of beta-lipoproteins are made in the intestine and liver. In the intestine, beta-lipoproteins include chylomicrons, which are formed as food is digested after a meal to carry dietary fats and cholesterol from the intestine to the bloodstream. Chylomicrons are also necessary for the absorption of certain fat-soluble vitamins, such as vitamins E, A, and K. In the liver, beta-lipoproteins include low-density lipoproteins (LDL) and very low-density lipoproteins (VLDL). These lipoproteins transport fats, cholesterol, and fat-soluble vitamins in the bloodstream to tissues throughout the body. Sufficient levels of fats, cholesterol, and vitamins are necessary for normal growth, development, and maintenance of the body's cells and tissues.

Health Conditions Related to Genetic Changes

Abetalipoproteinemia

More than 60 mutations in the MTTP gene have been found to cause abetalipoproteinemia. This condition impairs the normal absorption of fats and fat-soluble vitamins from the diet and primarily affects the gastrointestinal system, eyes, nervous system, and blood.

Most MTTP gene mutations lead to the production of microsomal triglyceride transfer protein with reduced or absent function, preventing the formation of beta-lipoproteins. One particular mutation is common in affected individuals of Ashkenazi (eastern and central European) Jewish descent; this mutation replaces the protein building block (amino acid) glycine with a premature stop signal at position 865 (written as Gly865Ter or G865X) in the instructions used to make the microsomal triglyceride transfer protein. As a result of this change, an abnormally small, nonfunctional version of the protein is made. All MTTP gene mutations that cause abetalipoproteinemia impair beta-lipoprotein formation and result in a severe shortage of chylomicrons, LDLs, and VLDLs. A lack of these lipoproteins prevents dietary fats and fat-soluble vitamins from being absorbed from the diet and transported through the bloodstream to the body's tissues. These nutritional deficiencies lead to health problems in people with abetalipoproteinemia.

Other Names for This Gene

• ABL
• microsomal TG transfer protein
• microsomal triglyceride transfer protein (large polypeptide, 88kD)
• microsomal triglyceride transfer protein large subunit
• MTP
• MTP triglyceride carrier
• MTP_HUMAN

Genomic Location

The signs and symptoms of abetalipoproteinemia usually appear in the first few months of life. They can include:

• inability to absorb fats and some vitamins
• poor growth in infancy
• digestive symptoms such as diarrhea and steatorrhea (foul-smelling stools)
• abnormal, star-shaped red blood cells (acanthocytosis)

Because abetalipoproteinemia is extremely rare, the course of the disease is difficult to predict. This condition is usually diagnosed in infancy due to diarrhea, vomiting and poor growth. Most individuals with this condition are treated with excess vitamins and a special, fat-controlled diet and have few complications. Untreated individuals with abetalipoproteinemia can develop gradual vision loss, muscle weakness, tremors, and slow or slurred speech that gets worse over time.

• nutritionist
• gastroenterologist
• hepatologist
• ophthalmologist
• neurologist