Introduction

Abetalipoproteinemia is a rare genetic condition with a predominance of less than 1 in 1 million.¹ It is an autosomal recessive condition, which means an individual may carry the mutated genes responsible for this condition but not have this condition. However, their children might develop it if both parents pass on the mutated gene.

The Mutations in the MTTP gene affect the microsomal triglyceride transfer protein (MTTP), which is responsible for producing and releasing apolipoprotein B-containing lipoproteins (important for fat transport) from the liver and intestines.² These lipoproteins are primarily cholesterol, low-density lipoproteins VLDL, and low-density lipoproteins LDL.³

In abetalipoproteinemia, these lipoproteins are very low in the plasma. This, in turn, affects the body’s ability to absorb fats and fat-soluble vitamins (A, D, E, K), which are key contributors to many physiological processes within the body.

This deficiency may manifest through gastrointestinal, neurological, visual and haematological symptoms. These include steatorrhea (fatty stools), diarrhoea, ataxia (poor coordination), neuropathy and cognitive disorders, retinitis pigmentosa and decreased vision, anaemia and acanthocytosis (deformed red blood cells).¹   

Major nutritional deficiencies

Fat-soluble vitamins

The fat-soluble vitamins affected in abetalipoproteinemia are vitamins A, D, E, and K. 

Vitamin A

Vitamin A plays a crucial role in maintaining eye health and supports the immune and reproductive systems. It improves vision in the dark and helps the body in its response against infections, in addition to its effect on fertility and conception. It is found in many foods like oily fish, liver products, carrots, spinach, and some dairy products. For adults aged 19 to 64, the daily requirement of vitamin A is 700 micrograms for men and 600 micrograms for women.⁴

A vitamin A deficiency can affect vision, mainly in the dark, as the eye cannot produce certain pigments that aid in the function of the retina. The retinal membrane might also start to experience some deterioration and further exacerbate the loss of night vision, which is characteristic of a disorder known as retinitis pigmentosa. If left untreated, this can eventually lead to blindness.⁵

Vitamin A is essential in forming and regulating immune cells and inflammatory responses.⁶ A deficiency in vitamin A also dampens the body’s response to fighting infections. This is mainly of concern for respiratory and gastrointestinal infections in children.⁷ It can moreover influence fertility in both males and females. Lack of vitamin A can inhibit the formation of sperm cells in males and hinder fertilisation and egg implantation in females.⁸

Vitamin D

Vitamin D is well known for its importance in maintaining good bone health and its effect on the immune system. Vitamin D is made in the body following exposure to UVB rays from direct sunlight. It is found in certain foods, such as oily fish, red meat, and egg yolk, or can be obtained from supplements.

Adults and children over the age of one need a regular daily dose of 10 micrograms to ensure adequate vitamin D supplementation. Vitamin D promotes bone formation and health by interacting with bone-forming cells (osteoblasts) and facilitating calcium and phosphate absorption from the intestines, which are important in bone formation. It also plays a role in the body’s immune response, as it is used by macrophages during the breakdown of bacteria.⁹

Low vitamin D levels can alter the bone composition and shape, resulting in diseases such as Rickets or osteomalacia. In both cases, the bones become softer and deformed, which is usually accompanied by pain and an increased risk of fractures. Children with these illnesses may also have problems with growth. Vitamin D deficiency may increase the incidence and duration of bacterial infections because it affects immunity.¹⁰ 

Vitamin E

Vitamin E is known to possess antioxidant properties, which help protect different cells from damage by free radicals released from food conversion in the body or the environment, such as from air pollutants and smoke. It is found in some plant oils and seeds or nuts. The daily recommended amount of vitamin E is 4 mg for men and 3 mg for women.¹¹

If vitamin E levels are low, damage can occur in muscles and nerves, manifesting as muscle weakness and loss of balance (ataxia). It can also cause peripheral neuropathy, in which there is tingling or numbness in the extremities. Some research also suggests that vitamin E plays a role in the immune system and that its deficiency increases the likelihood of infections.¹²

Vitamin K

Vitamin K plays a crucial role in the body's clotting processes, cardiovascular health, and bone strength. It is essential for the production of clotting factors like prothrombin. It is found mainly in leafy greens. Adults need 1 microgram per kilogram of body weight of Vitamin K on a regular basis.^13,14

A vitamin K deficiency may present in the form of excessive bleeding and difficulty for blood to clot. There may also be an increased risk of bruising easily, and gastrointestinal bleeding detected by the presence of blood in stools.¹⁵

Secondary nutritional deficiencies

Minerals and trace elements

Calcium

Calcium is essential for maintaining strong bones and ensuring proper muscle and heart contractions. It is found in dairy products like milk, cheese, and certain fortified flours or drinks. An adult requires 700 mg of calcium per day to maintain an adequate supply for proper functioning of the body. The absorption of calcium is affected in patients with abetalipoproteinemia as it is mediated by vitamin D, which is low in this condition. Consequently, bone health is affected, and the risk of bone deformities and fractures increases. This may eventually lead to the development of Rickets or osteomalacia, in which the bones become soft and are associated with pain.¹⁵

Magnesium

Magnesium is another important mineral that contributes to many functions of the body, namely in metabolic reactions and muscle contractions. It is found primarily in leaves, and an adult needs 270-300 mg of magnesium every day to sustain adequate levels in the body. The signs of magnesium deficiency include muscle shaking, fatigue, and irregular heartbeats. It is also accompanied by low calcium levels, as both their absorptions are influenced by vitamin D.¹⁶ 

Management and treatment

Patients with abetalipoproteinemia require dietary modifications to support the body's normal functioning and correct the deficiency that results from this condition. Since abetalipoproteinemia is a genetic disorder, treatment aims to manage the symptoms and reduce their severity and progression. A diet low in fats is highly recommended as the body loses its ability to absorb them, which causes their presence in stools. It also aids in alleviating diarrhoea and any further vitamin deficiencies associated with it.^3,6

Supplementation with high doses of vitamins A, D, E, and K is very crucial in managing the conditions resulting from low levels of these vitamins. These supplements may be given orally or by injection, although the former is more common. Regular monitoring of serum levels of these vitamins, as well as other minerals and electrolytes such as calcium and magnesium, aids in making sure adequate levels are constantly present in the body. Patients should be referred to a nutritionist to provide them with a personalised diet plan to improve their condition. Anaemia can result from acanthocytosis or bleeding caused by a vitamin K deficiency. Iron and folate levels should be monitored, and supplements should be offered if anaemia is suspected.¹⁷ 

Summary

Abetalipoproteinemia is a rare genetic disorder inherited when both parents carry the mutated genes that cause the condition. It affects the body’s ability to absorb fats and fat-soluble nutrients, leading to a myriad of systemic dysfunctions caused by severe nutritional deficiencies. Vitamins A, D, E, and K are affected by this disorder. Certain minerals, like calcium and magnesium, may also be affected. These vitamins are key in many processes throughout the body, and their absence affects key organs like the eyes, bones, blood, and immune system. Their deficiencies carry with them a risk of blindness, soft and brittle bones, distorted red blood cells, increased bleeding, and possibly a slower response to infections. The management of abetalipoproteinemia focuses on managing symptoms by reducing fat intake and correcting the depletion of the aforementioned vitamins through proper supplementation. Regular monitoring and blood work are required to ensure vitamin levels are within range at all times and that symptoms are either stable or improving.