Abetalipoproteinemia is a condition characterized by the inability to fully absorb dietary fats, cholesterol and fat-soluble vitamins. The resulting insufficiency of fats and vitamins affect the normal development and function of the body. Signs and symptoms appear in the first few months of life and can include failure to thrive; diarrhea; acanthocytosis; and stool abnormalities. Other features develop later in childhood and often impair the function of the nervous system, potentially causing slower intellectual development; poor muscle coordination; progressive ataxia; and an eye disorder called retinitis pigmentosa. Most of the symptoms are due to defects in the absorption and transport of vitamin E. Abetalipoproteinemia is caused by mutations in the MTTP gene and is inherited in an autosomal recessive manner. Early diagnosis, high-dose vitamin E therapy, and medium-chain fatty acid supplements may slow the progression of the nervous system abnormalities. Long-term outlook is reasonably good for most affected people who are diagnosed early. If left untreated, the condition can result in early death.
The signs and symptoms of abetalipoproteinemia usually appear in the first few months of life. They can include:
failure to thrive in infancy
- Digestive symptoms such as diarrhea and steatorrhea (foul-smelling stools)
- Abnormal, star-shaped red blood cells (acanthocytosis)
- Nervous system (neurologic) symptoms beginning in childhood such as slower intellectual development; peripheral neuropathy; poor muscle coordination; ataxia; and intention tremors
- Eye (ophthalmologic) symptoms such as decreased night and color vision; retinitis pigmentosa in adolescence; and gradual deterioration of vision, often leading to blindness in the fourth decade of life
- Absence of apoprotein B-100
- Low/absent serum betalipoproteins
- Motor incoordination
- Retinitis pigmentosa
- Neurological symptoms
- Muscle weakness
- Balance and coordinationproblems
- Degeneration of the retina
- Loss of vision
- Failure to thrive/Failure to grow in infancy
- Steatorrhea/Fatty, pale stools
- Frothy stools
- Foul smelling stools
- Protruding abdomen
- Intellectual disability/developmental delay
- Developmental coordination disorder, evident by age ten
- Slurred speech
- Scoliosis (curvature of the spine)
- Progressive decreased vision
- Balance and coordination problems
Abetalipoproteinemia is caused by changes (mutations) in the MTTP gene. The MTTP gene gives the body instructions to make a protein needed for creating beta-lipoproteins. These lipoproteins are necessary for the body to absorb fats, cholesterol, and fat-soluble vitamins (vitamins A, D, E and K), and for transporting these substances in the blood. Mutations in the MTTP result in a lack of beta-lipoproteins, leading to an inability to absorb and transport these substances. This in turn leads to the nutritional and neurologic problems in affected people.
It is an autosomal recessive condition that more often affects males. This means that to be affected, a person must have a mutation in both copies of the responsible gene in each cell. Affected people inherit one mutated copy of the gene from each parent, who is referred to as a carrier. Carriers of an autosomal recessive condition typically do not have any signs or symptoms (they are unaffected). When 2 carriers of an autosomal recessive condition have children, each child has a:
- 25% (1 in 4) chance to be affected
- 50% (1 in 2) chance to be an unaffected carrier like each parent
- 25% chance to be unaffected and not be a carrier
The inability to absorb fat in the ileum will result in steatorrhea, or fat in the stool. As a result, this can be clinically diagnosed when foul-smelling stool is encountered. Low levels of plasma chylomicron are also characteristic. Acanthocytes are seen on blood smear.
There is an absence of apolipoprotein B. On intestinal biopsy, vacuoles containing lipids are seen in enterocytes. Since there is no or little assimilation of chylomicrons, their levels in plasma remains low. This disorder may also result in fat accumulation in the liver (hepatic steatosis). Because the epithelial cells of the bowel lack the ability to place fats into chylomicrons, lipids accumulate at the surface of the cell, crowding the functions that are necessary for proper absorption.
If treatment is initiated early in disease the neurologic sequelae may be reversed and further deterioration can be prevented. How well a patient does depends on the amount of brain and nervous system problems. The long-term outlook (prognosis) is reasonably good for most people who are diagnosed and treated early. However, how well each person does depends on the amount of brain and nervous system problems. Therefore, the prognosis can vary. People with prolonged vitamin deficiency, especially of vitamin E, may develop very limiting ataxia and gait disturbances. Some people may develop retinal degeneration and blindness.
A nutritionist or other qualified medical professional should be consulted for specific dietary instruction in people with abetalipoproteinemia. Treatment involves very large doses of vitamin E, as well as large doses of vitamin supplements containing other fat-soluble vitamins (vitamin A, vitamin D, and vitamin K). Linoleic acid supplements are also recommended.
Several diet changes and/or restrictions are also needed to prevent stomach problems. A low-fat diet may help with digestive symptoms; medium chain triglycerides may be used (under supervision of a specialist) as a source of fat in the diet.
Management in adults typically focuses on specific complications associated with the disorder, and depends on the signs and symptoms present. Affected people may need consultations with several other types of specialists, including a lipidologist, gastroenterologist, hepatologist, ophthalmologist, and neurologist.
The list of treatments mentioned in various sources for Abetalipoproteinemia includes the following list. Always seek professional medical advice about any treatment or change in treatment plans.
- Vitamin A + Vitamin E
- Vitamin E - possibly used for treatment of related Vitamin E deficiency