Abetalipoproteinemia (also known as: Bassen–Kornzweig syndrome, microsomal triglyceride transfer protein deficiency disease, MTP deficiency, and betalipoprotein deficiency syndrome) is a disorder characterized by abnormal absorption of fat and fat-soluble vitamins from food. It is caused by a mutation in microsomal triglyceride transfer protein resulting in deficiencies in the apolipoproteins B-48 and B-100, which are used in the synthesis and exportation of chylomicrons and VLDL respectively. It is not to be confused with familial dysbetalipoproteinemia.
It is a rare autosomal recessive disorder.
Presentation
Symptoms
Initial symptoms usually appear in infancy,
- Steatorrhea (i.e. fatty, pale stools)
- Frothy stools
The rate of occurrence of additional symptoms later in life varies and increases with age. These may include:
- Intellectual disability/developmental delay
- Retinitis pigmentosa and progressive degeneration of the retina (the light-sensitive layer in the posterior eye) that can progress to near-blindness (due to deficiency of vitamin A, retinol). (apolipoprotein B deficiency, a related condition, is associated with deficiencies of apolipoprotein B).
The MTTP gene provides instructions for making a protein called microsomal triglyceride transfer protein, which is essential for creating beta-lipoproteins. These lipoproteins are both necessary for the absorption of fats, cholesterol, and fat-soluble vitamins from the diet and necessary for the efficient transport of these substances in the bloodstream. Most of the mutations in this gene lead to the production of an abnormally short microsomal triglyceride transfer protein, which prevents the normal creation of beta-lipoproteins in the body. MTTP-associated mutations are inherited in an autosomal recessive pattern, which means both copies of the gene must be faulty to produce the disease. Skeletal system developments often include lordosis, kyphoscoliosis, or pes cavus.
Diagnosis
The initial workup of Abetalipoproteinemia typically consists of stool sampling, a peripheral blood smear, and a fasting lipid panel, though these tests are not confirmatory. As the disease is rare, though a genetics test is necessary for diagnosis, it is generally not done initially. However, prenatal testing may be available for pregnancies identified to be at an increased risk (if both parents are unaffected carrier or one parent is affected and the other in a carrier).{}
Acanthocytes are seen on blood smear. Since there is no or little assimilation of chylomicrons, their levels in plasma remains low.
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.
There is an absence of apolipoprotein B. On intestinal biopsy, vacuoles containing lipids are seen in enterocytes. 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.
Multiple related disorders present with similar symptoms as abetalipoproteinemia that can provide a useful diagnosis through comparisons. Some of those disorders are:
Treatment
Treatment normally consists of rigorous dieting, involving massive amounts of vitamin E. Long-term outlook is reasonably good for most people when diagnosed and treated early. A case study presented a female patient diagnosed at the age of 11. Despite the relatively late diagnosis, the patient married and at the age of 34, gave birth to a full-term healthy infant. Her medication included vitamin K 10 mg twice a week, beta-carotene 40,000 IU daily, vitamin A 10,000 IU daily, vitamin E 400 IU daily, vitamins B6 and B12, calcium, magnesium and eye drops.
Prolonged vitamin deficiencies can further compromise health. Specifically, a prolonged vitamin E deficiency can lead to the development of limiting ataxia and gait disturbances. Some individuals may develop retinal degeneration and blindness. If left untreated, the condition may lead to death.'
More recent research has focused on different ways to supply the patient with vitamin E. In 2018, the Journal of Lipid Research published a study testing alternative forms of vitamin E absorption. Currently, vitamin E is most often supplemented in the fat-soluble form vitamin E acetate. Due to fat malabsorption, the intended supplementation is considerably compromised. Two different forms were tested: vitamin E tocofersolan and α-tocopherol acetate. The study concluded that plasma bioavailabilities were extremely low (2.8% and 3.1%, respectively). Additionally, plasma concentrations of tocopherol were not significantly different in patients.
This study provides new insight in vitamin E supplementation and suggests further research is needed with different forms of vitamin E as possible treatment options to abetalipoproteinemia.
Currently, there is a clinical study recruiting abetalipoproteinemia patients to study inherited retinal degenerative disease. There is also a second clinical study, currently under recruitment, to investigate the consequences of deficiencies in lipophilic nutrients in this disease, such as lutein and carotenes, on retinal macular function.