Abetalipoproteinemia
Encyclopedia
Abetalipoproteinemia, or Bassen-Kornzweig syndrome, is a rare autosomal recessive disorder that interferes with the normal absorption of fat and fat-soluble vitamins from food. It is caused by a deficiency of apolipoprotein 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
.
, and certain vitamin
s. People affected by this disorder are not able to make certain lipoprotein
s, which are molecule
s that consist of protein
s combined with cholesterol and particular fats called triglyceride
s. This leads to a multiple vitamin deficiency, affecting the fat-soluble vitamin A
, vitamin D
, vitamin E
, and vitamin K
. However, many of the observed effects are due to vitamin E deficiency in particular.
The signs and symptoms of abetalipoproteinemia appear in the first few months of life(because pancreatic lipase is not active in this period). They can include failure to gain weight and grow at the expected rate (failure to thrive); diarrhea; abnormal star-shaped red blood cells (acanthocytosis
); and fatty, foul-smelling stools (steatorrhea
). The stool may contain large chunks of fat and/or blood. Other features of this disorder may develop later in childhood and often impair the function of the nervous system. They can include poor muscle coordination, difficulty with balance and movement (ataxia
), and progressive degeneration of the light-sensitive layer (retina) at the back of the eye that can progress to near-blindness(due to deficiency of Vitamin A,retinol). Adults in their thirties or forties may have increasing difficulty with balance and walking. Many of the signs and symptoms of abetalipoproteinemia result from a severe vitamin deficiency, especially vitamin E deficiency, which typically results in eye problems with degeneration of the spinocerebellar and dorsal columns tracts.
, 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
, vacuole
s containing lipids are seen in enterocytes. Since there is no or little assimilation of chylomicron
s, 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.
Mutations in the microsomal triglyceride transfer protein
(MTTP) gene has been associated with this condition. (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.
. Vitamin E helps the body restore and produce lipoproteins, which people with abetalipoprotenimia usually lack. Vitamin E also helps keep skin and eyes healthy; studies show that many affected males will have vision problems later on in life. Dyspraxia and muscle weakness are usually treated with physiotherapy or occupational therapy
. Dietary restriction of triglyceride
s has also been useful.
Familial dysbetalipoproteinemia
Familial dysbetalipoproteinemia is a condition characterized by increased LDL, triglyceride, and cholesterol levels, and decreased HDL levels...
.
Features
Abetalipoproteinemia affects the absorption of dietary fats, cholesterolCholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
, and certain vitamin
Vitamin
A vitamin is an organic compound required as a nutrient in tiny amounts by an organism. In other words, an organic chemical compound is called a vitamin when it cannot be synthesized in sufficient quantities by an organism, and must be obtained from the diet. Thus, the term is conditional both on...
s. People affected by this disorder are not able to make certain lipoprotein
Lipoprotein
A lipoprotein is a biochemical assembly that contains both proteins and lipids water-bound to the proteins. Many enzymes, transporters, structural proteins, antigens, adhesins, and toxins are lipoproteins...
s, which are molecule
Molecule
A molecule is an electrically neutral group of at least two atoms held together by covalent chemical bonds. Molecules are distinguished from ions by their electrical charge...
s that consist of protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s combined with cholesterol and particular fats called triglyceride
Triglyceride
A triglyceride is an ester derived from glycerol and three fatty acids. There are many triglycerides, depending on the oil source, some are highly unsaturated, some less so....
s. This leads to a multiple vitamin deficiency, affecting the fat-soluble vitamin A
Retinol
Retinol is one of the animal forms of vitamin A. It is a diterpenoid and an alcohol. It is convertible to other forms of vitamin A, and the retinyl ester derivative of the alcohol serves as the storage form of the vitamin in animals....
, vitamin D
Vitamin D
Vitamin D is a group of fat-soluble secosteroids. In humans, vitamin D is unique both because it functions as a prohormone and because the body can synthesize it when sun exposure is adequate ....
, vitamin E
Tocopherol
Tocopherols are a class of chemical compounds of which many have vitamin E activity. It is a series of organic compounds consisting of various methylated phenols...
, and vitamin K
Vitamin K
Vitamin K is a group of structurally similar, fat soluble vitamins that are needed for the posttranslational modification of certain proteins required for blood coagulation and in metabolic pathways in bone and other tissue. They are 2-methyl-1,4-naphthoquinone derivatives...
. However, many of the observed effects are due to vitamin E deficiency in particular.
Acanthocyte
Acanthocyte, in human biology and medicine, refers to a form of red blood cell that are spiked, or possess various abnormal thorny projections. Acanthocytosis is the condition with acanthocyte-like red blood cells....
); and fatty, foul-smelling stools (steatorrhea
Steatorrhea
Steatorrhea is the presence of excess fat in feces. Stools may also float due to excess lipid, have an oily appearance and be especially foul-smelling. An oily anal leakage or some level of fecal incontinence may occur. There is increased fat excretion, which can be measured by determining the...
). The stool may contain large chunks of fat and/or blood. Other features of this disorder may develop later in childhood and often impair the function of the nervous system. They can include poor muscle coordination, difficulty with balance and movement (ataxia
Ataxia
Ataxia is a neurological sign and symptom that consists of gross lack of coordination of muscle movements. Ataxia is a non-specific clinical manifestation implying dysfunction of the parts of the nervous system that coordinate movement, such as the cerebellum...
), and progressive degeneration of the light-sensitive layer (retina) at the back of the eye that can progress to near-blindness(due to deficiency of Vitamin A,retinol). Adults in their thirties or forties may have increasing difficulty with balance and walking. Many of the signs and symptoms of abetalipoproteinemia result from a severe vitamin deficiency, especially vitamin E deficiency, which typically results in eye problems with degeneration of the spinocerebellar and dorsal columns tracts.
Symptoms
Often symptoms will arise that indicate the body is not absorbing or making the lipoproteins that it needs. These symptoms usually appear en masse, meaning that they happen all together, all the time. These symptoms come as follows:- Failure to grow in infancy
- Fatty, pale stools
- Frothy stools
- Foul smelling stools
- Protruding abdomen
- Mental retardationMental retardationMental retardation is a generalized disorder appearing before adulthood, characterized by significantly impaired cognitive functioning and deficits in two or more adaptive behaviors...
/developmental delay - DyspraxiaDyspraxiaDevelopmental dyspraxia is a motor learning difficulty that can affect planning of movements and co-ordination as a result of brain messages not being accurately transmitted to the body...
, evident by age ten - Muscle weakness
- Slurred speech
- ScoliosisScoliosisScoliosis is a medical condition in which a person's spine is curved from side to side. Although it is a complex three-dimensional deformity, on an X-ray, viewed from the rear, the spine of an individual with scoliosis may look more like an "S" or a "C" than a straight line...
(curvature of the spine) - Progressive decreased vision
- Balance and coordination problems
- Retinitis Pigmentosa
Diagnosis
The inability to absorb fat in the ileum will result in steatorrheaSteatorrhea
Steatorrhea is the presence of excess fat in feces. Stools may also float due to excess lipid, have an oily appearance and be especially foul-smelling. An oily anal leakage or some level of fecal incontinence may occur. There is increased fat excretion, which can be measured by determining the...
, or fat in the stool. As a result, this can be clinically diagnosed when foul-smelling stool is encountered. Low levels of plasma chylomicron
Chylomicron
Chylomicrons are lipoprotein particles that consist of triglycerides , phospholipids , cholesterol and proteins .They transport dietary lipids from the intestines to other locations in the body...
are also characteristic. Acanthocytes are seen on blood smear.
There is an absence of apolipoprotein B
Apolipoprotein B
Apolipoprotein B is the primary apolipoprotein of low-density lipoproteins , which is responsible for carrying cholesterol to tissues. While it is unclear exactly what functional role APOB plays in LDL, it is the primary apolipoprotein component and is absolutely required for its formation...
. On intestinal biopsy
Biopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
, vacuole
Vacuole
A vacuole is a membrane-bound organelle which is present in all plant and fungal cells and some protist, animal and bacterial cells. Vacuoles are essentially enclosed compartments which are filled with water containing inorganic and organic molecules including enzymes in solution, though in certain...
s containing lipids are seen in enterocytes. Since there is no or little assimilation of chylomicron
Chylomicron
Chylomicrons are lipoprotein particles that consist of triglycerides , phospholipids , cholesterol and proteins .They transport dietary lipids from the intestines to other locations in the body...
s, their levels in plasma
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
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.
Genetics
Microsomal triglyceride transfer protein
Microsomal triglyceride transfer protein large subunit is a protein that in humans is encoded by the MTTP gene.Apoprotein B48 on chylomicra and Apoprotein B100 on LDL, IDL, and VLDL are important for MTP binding.-Interactive pathway map:...
(MTTP) gene has been associated with this condition. (Apolipoprotein B deficiency
Apolipoprotein B deficiency
Apolipoprotein B deficiency is an autosomal dominant disorder resulting from a missense mutation which reduces the affinity of apoB-100 for the low-density lipoprotein receptor Apolipoprotein B deficiency (also known as "Familial defective apolipoprotein B-100") is an autosomal dominant disorder...
, a related condition, is associated with deficiencies of apolipoprotein B
Apolipoprotein B
Apolipoprotein B is the primary apolipoprotein of low-density lipoproteins , which is responsible for carrying cholesterol to tissues. While it is unclear exactly what functional role APOB plays in LDL, it is the primary apolipoprotein component and is absolutely required for its formation...
.)
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
Recessive
In genetics, the term "recessive gene" refers to an allele that causes a phenotype that is only seen in a homozygous genotype and never in a heterozygous genotype. Every person has two copies of every gene on autosomal chromosomes, one from mother and one from father...
pattern, which means both copies of the gene must be faulty to produce the disease.
Treatment
Treatment normally consists of rigorous dieting, involving mass amounts of vitamin EVitamin E
Vitamin E is used to refer to a group of fat-soluble compounds that include both tocopherols and tocotrienols. There are many different forms of vitamin E, of which γ-tocopherol is the most common in the North American diet. γ-Tocopherol can be found in corn oil, soybean oil, margarine and dressings...
. Vitamin E helps the body restore and produce lipoproteins, which people with abetalipoprotenimia usually lack. Vitamin E also helps keep skin and eyes healthy; studies show that many affected males will have vision problems later on in life. Dyspraxia and muscle weakness are usually treated with physiotherapy or occupational therapy
Occupational therapy
Occupational therapy is a discipline that aims to promote health by enabling people to perform meaningful and purposeful activities. Occupational therapists work with individuals who suffer from a mentally, physically, developmentally, and/or emotionally disabling condition by utilizing treatments...
. Dietary restriction of triglyceride
Triglyceride
A triglyceride is an ester derived from glycerol and three fatty acids. There are many triglycerides, depending on the oil source, some are highly unsaturated, some less so....
s has also been useful.