Introduction

Most of us have heard of rare diseases such as cystic fibrosis or Amyotrophic Lateral Sclerosis, which is also commonly abbreviated as ALS. You might remember back in 2014, the ALS ice bucket challenge, which was to raise awareness for the ALS disease. In this article, we’ll explore a disease so rare that your chances of finding a four-leaf clover or even being struck by lightning are far greater than encountering it. This disease is called Abetalipoproteinemia (ABL), and this tongue-twister disease has been reported to have occurred in about 1 in a million people.¹ One organ that ABL can affect is the liver. As we know, liver health is vital for people to live a healthy lifestyle as it has many functions such as detoxing the blood, managing our metabolism and producing bile, which ABL can disrupt. As we read further, we will explore healthy liver function, what ABL is and how this disease can affect the liver. 

Normal liver function

The liver is a vital organ that performs an array of different functions. It is extremely important for the metabolism of the three macronutrients(carbohydrates, proteins, and fats) contained within the food you eat. The liver can also store glycogen and fats. It also serves a role in detoxifying the blood by using cells called hepatocytes. These cells carry out lots of different complex chemical reactions that filter the blood from harmful substances such as alcohol, waste products produced by the body that are released into the bloodstream and even medication that you consume. Another essential function of the liver is the production of bile, which helps to break down fats in the small intestine which allowing them to be absorbed. There are many more tasks that the liver carries out, and it is important to recognise that the body relies on this organ in order to survive.

What is abetalipoproteinemia?

This is a rare inherited genetic mutation in the MTTP gene, which typically presents in infancy. The MTTP gene codes for a protein called the microsomal triglyceride protein (MTP).¹ This protein is important for the production of a lipoprotein called chylomicrons and other lipoproteins that contain apoB.² These lipoproteins are required for the transport of fats that you consume, as they are not able to dissolve in blood plasma. These fats are then absorbed through the small intestine (with the help of bile) into the bloodstream, and these dietary fats are used for different bodily functions. When the MTTP gene has mutated, fats and fat-soluble vitamins, which cannot be properly absorbed, will struggle to be absorbed into the bloodstream, such as vitamin A, D, E, and K. This is called malabsorption. The malabsorption of fats creates huge systemic effects on the body, such as visual problems, acanthocytosis (irregular shape of red blood cells) and spinocerebellar degeneration.¹ 

More common symptoms include, but are not limited to:

• Failure to thrive
• Diarrhoea
• Fatty, foul-smelling stools (steatorrhea)
• Muscle weakness and muscle loss
• Vision problems
• Nerve damage, involving numbness in the limbs and problems with coordination
• Liver disease
• Intellectual disability

How is the liver function affected? 

The liver is affected by the accumulation of fat known as steatosis.³ This is due to an imbalance and buildup of fats as they struggle to be transported due to the lack of chylomicrons and apoB to help assist them, as the liver synthesises fatty acids and receives other fatty acids from the bloodstream.⁴ You may also know steatosis as nonalcoholic fatty liver disease (NAFLD). This could also potentially lead to scarring of the liver (fibrosis or cirrhosis) and cause appetite loss and persistent nausea, which may lead to unintended weight loss. Another consequence of the buildup of fat in the liver is hepatomegaly, which is where the liver increases in size and enlarges to the point of discomfort. A doctor will be able to physically feel the liver during an examination.³ 

How is abetalipoproteinemia diagnosed?

Doctors will carry out clinical evaluations on the patient by examining the levels of LDL-Cholesterol, triglycerides (fatty acids) and apoB levels through blood tests. If these levels are very low, the doctor will opt to carry out molecular genetic testing for MTTP gene mutations. Another method would be carrying out a complete neurological assessment and an eye examination to check for more symptoms. Further blood tests can be taken to check for fat-soluble vitamin levels and identify the malformed red blood cells (acanthocytosis).³

Management and treatment

It is possible to live with ABL, however, it can be very challenging for both the child and their parents. Parents will have to feed their child a low-fat diet to relieve the gastrointestinal symptoms and frequently supplement with fat-soluble vitamins to avoid vitamin deficiencies.¹ The low-fat diet must specifically restrict foods that contain long-chain fatty acids such as olive oil, palm kernel oil, fish, nuts and meat, which can be very difficult to avoid. However, they can have foods that have medium-chain fatty acids, as they can be absorbed without the need for lipoproteins, such as coconut oil. The child may also have to undergo physiotherapy due to the neurodegenerative nature of the disease, if not diagnosed early enough. However, if treated early with vitamin A and E supplementation, this can be prevented. Patients will be monitored consistently, as this disease may inhibit the growth of the child, so it would be important to examine the child comprehensively with many different specialists so that the child can have an easier childhood.⁵

Living with abetalipoproteinemia

Living with ABL can be extremely difficult and will affect the quality of life of both the child and the parents. There are many long-term effects that this disease can have if not carefully monitored and treated. Therefore, it is important to diagnose this disease and intervene immediately. If you are a parent who has a child with ABL, just know that you are not alone, and although the disease itself is very rare, the research is very extensive, and support is available for both you and your child. This condition can be very mentally taxing and affect your quality of life. If a loved one has a child with this condition, offer your support in any way you can to help ease their burden.⁶

Summary

Abetalipoproteinemia is a rare recessive genetic disorder that is caused by the mutated MTTP gene, which reduces the production of lipoproteins to help absorb dietary fats and fat-soluble vitamins such as vitamin E. This can lead to complications in infants that can affect their growth and development. It is diagnosed by examining serum lipid levels via a blood test and genetic screening for a mutation in the MTTP gene. When diagnosed, it is then treated by a low-fat diet and is heavily supplemented with fat-soluble vitamins.

FAQs

Q. Why not just check for chylomicron levels when diagnosing?

A. This is because chylomicrons and other “low-density” lipoproteins are not detectable in the blood plasma.^{2, 3}

Q. Can a child outgrow ABL?

A. Sadly, this is not possible, and it is lifelong.