Overview

Abetalipoproteinemia is a rare inherited disorder that impairs the absorption of fat and fat-soluble vitamins in the intestine and liver.¹ The body’s inability to absorb fat results in a deficiency of lipids and essential vitamins, which can cause a deterioration in mental ability and eyesight, along with the muscles weakening. 

Abetalipoproteinemia is an autosomal recessive disorder, which means that the condition is inherited and affects one of the numbered chromosomes within your DNA. This is caused by a biallelic mutation in the MTTP gene, that is responsible for providing the instructions to create a protein called microsomal triglyceride transfer protein.¹ This protein aids in the production of molecules known as beta-lipoproteins that are made from proteins, cholesterol and specific types of fats, called phospholipids and triglycerides. There are different types of beta-lipoproteins made in the intestines and liver. Beta-lipoproteins in the liver contain chylomicrons that are essential in the absorption of fat-soluble vitamins (A, E, and K).  Alongside low and very low-density lipoproteins that transport fats, fat-soluble vitamins and cholesterol throughout the body. A sufficient level of fats, fat-soluble vitamins and cholesterol are important for normal growth, development, and maintenance of the body, its cells and tissues.² 

Early clinical features of Abetalipoproteinemia 

People diagnosed with abetalipoproteinemia can experience a variety of symptoms that can affect many different parts of the body, including the digestive system, brain, eyes and blood. 

Infants can be affected by abetalipoproteinemia typically present with symptoms that are similar to gastrointestinal disease. Such symptoms include:

• Loose, pale foul-smelling stools (steatorrhea)
• Diarrhoea
• Vomiting
• Swelling or bloating of the stomach
• Failure to thrive (minimal weight gain and growth)

These symptoms are a result of poor fat absorption from their diet. With poor fat absorption, there is a decrease in the ability to absorb important fat-soluble vitamins, such as vitamins A, E, and K, which may lead to the formation of a deficiency.  

Neurological symptoms 

From the ages of 2 to 20 years, a variety of different neurological conditions can occur that resemble spinocerebellar degeneration, which is the general name for a group of inherited brain disorders that impair the ability to coordinate voluntary movement, as a result of progressive degeneration of certain structures in the brain, called the cerebellar ataxia. Symptoms that may occur as a result of this include:

• Lack of coordination
• Decline in voluntary movement
• Muscle weakness
• Loss of deep tendon reflexes
• Tremors and tics
• Slurred speech

In some cases, the peripheral nervous system may become damaged. The peripheral nervous system houses all of the nerves that are outside of the central nervous system. Damage or malfunction of the peripheral nervous system can cause symptoms such as:

• Numbness and tingling of the arms and legs
• A burning sensation over the body and limbs
• Muscle weakness

Less commonly, some people may experience symptoms that affect their eyes and vision, such as the progressive degenerative disorder called retinitis pigmentosa. Retinitis pigmentosa affects the nerve-rich membrane that lines the eyes, causing symptoms like:

• Tunnel vision
• Loss of ability to see colour
• Night blindness
• Loss of visual acuity 

Retinitis pigmentosa usually begins around age 10, and if left untreated, can result in a total loss of visual acuity, leading to blindness in adulthood. This disorder is thought to be caused by a deficiency in vitamin A and/or E.³  Other symptoms that may affect the eyes include: 

• Fast, involuntary eye movements
• Crossed eyes 
• Different sized pupils
• Weakness or paralysis of eye muscles
• Sagging of the bottom eyelid 

Haematological symptoms 

Abetalipoproteinemia may cause blood abnormalities, mainly causing a condition called acanthocytosis to develop. Acanthocytosis is a condition where the red blood cells in the body are deformed, which can lead to a decrease in red blood cells circulating in the bloodstream.  Other blood abnormalities could be caused by a deficiency in vitamin K, an important factor in blood clotting.³  

A decrease in circulating red blood cells can result in the development of anaemia. The symptoms of anaemia include: 

• Tiredness and fatigue
• Weakness 
• Dizziness
• Irritability 
• Heart palpitations
• Pale skin

Musculoskeletal symptoms 

Skeletal deformities can occur due to imbalances in muscle during the crucial stages of bone development, likely from a deficiency of certain vitamins. Over time, affected individuals may find that they are unable to walk or stand unaided, due to the progressive nature of their neurological and skeletal abnormalities. Specific conditions caused by skeletal deformities are:

• Lumbar lordosis (extreme curvature of the spine)
• Scoliosis (irregular curvature of the spine)
• Kyphoscoliosis
• Over arched foot
• Club foot

Impact and quality of life 

The impact of abetalipoproteinemia can be severe, debilitating, and life-threatening if left untreated, significantly reducing the life expectancy due to the development of complications.¹ 

The use of vitamins A and E as treatment has been reported to slow the progression of the disease and prevent further complications from developing.⁴

Summary

Abetalipoproteinemia is a rare, inherited disorder characterised by an inability to absorb fat and fat-soluble vitamins in the intestine and liver, leading to a deficiency in fat-soluble vitamins which can cause several complications in the body. Abetalipoproteinemia is caused by a mutation in the gene (MTTP) that makes specific transport proteins responsible for carrying fats, fat-soluble vitamins, and cholesterol throughout the body to the tissues. Fats and fat-soluble vitamins are essential in regulating the growth and development of the body. 

Symptoms of abetalipoproteinemia can vary depending on the part of the body that is affected, such as the brain, eyes, skeleton, muscles, digestive system, and blood. Common symptoms in infants are similar to those of gastrointestinal disease, whilst adults may experience symptoms of multiple progressive degenerative disorders, such as ataxia and retinitis pigmentosa. A blood disorder called acanthocytosis, where the red blood cells are deformed, is common in affected individuals and can lead to the development of anaemia due to a decrease in red blood cells circulating throughout the body. 

Abetalipoproteinemia is a serious condition, and its complications can be debilitating and at worst, fatal if left untreated. It is important to seek the appropriate treatment from a specialist doctor.