Abetalipoproteinemia

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Abetalipoproteinemia is an inherited disorder that impairs the normal absorption of fats and certain vitamins from the diet. Many of the signs and symptoms of abetalipoproteinemia result from a severe shortage (deficiency) of fat-soluble vitamins (vitamins A, E, and K). The signs and symptoms of this condition primarily affect the gastrointestinal system, eyes, nervous system, and blood.

The first signs and symptoms of abetalipoproteinemia appear in infancy. They often include an inability to grow and gain weight at the expected rate (faltering weight); diarrhea; and fatty, foul-smelling stools (steatorrhea).

As an individual with this condition ages, additional signs and symptoms include disturbances in nerve function that may lead to poor muscle coordination and difficulty with balance and movement (ataxia). They can also experience a loss of certain reflexes, impaired speech (dysarthria), tremors or other involuntary movements (motor tics), a loss of sensation in the extremities (peripheral neuropathy), or muscle weakness. The muscle problems can disrupt skeletal development, leading to an abnormally curved lower back (lordosis), a rounded upper back that also curves to the side (kyphoscoliosis), high-arched feet (pes cavus), or an inward- and upward-turning foot (clubfoot).

Individuals with this condition may also develop an eye disorder called retinitis pigmentosa, in which breakdown of the light-sensitive layer (retina) at the back of the eye can cause vision loss. In individuals with abetalipoproteinemia, the retinitis pigmentosa can result in complete vision loss. People with abetalipoproteinemia may also have other eye problems, including involuntary eye movements (nystagmus), eyes that do not look in the same direction (strabismus), and weakness of the external muscles of the eye (ophthalmoplegia).

Individuals with abetalipoproteinemia usually have a low number of red blood cells (anemia) with abnormally star-shaped red blood cells (acanthocytosis) and have difficulty forming blood clots, which can cause abnormal bleeding. In some cases, a condition called fatty liver develops, which can cause liver damage.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Abetalipoproteinemia is caused by mutations in the MTTP gene, which provides instructions for making a protein called microsomal triglyceride transfer protein. This protein is essential for creating molecules called beta-lipoproteins in the liver and intestine. Beta-lipoproteins transport fats, cholesterol, and fat-soluble vitamins from the intestine to the bloodstream so these nutrients can be taken up by tissues throughout the body. Sufficient levels of fats, cholesterol, and vitamins are necessary for normal growth, development, and maintenance of the body's cells and tissues.

Most MTTP gene mutations lead to the production of microsomal triglyceride transfer protein with reduced or absent function and unable to help in the formation of beta-lipoproteins. A lack of beta-lipoproteins causes severely reduced absorption (malabsorption) of dietary fats and fat-soluble vitamins from the digestive tract into the bloodstream. These nutritional deficiencies lead to health problems in people with abetalipoproteinemia.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Abetalipoproteinemia is a rare disorder. More than 100 cases have been described worldwide.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Abnormal circulating apolipoprotein concentration · Very frequent (99-80%)

Any deviation from the normal concentration of apolipoprotein in the blood circulation.

Abnormality of the nervous system · Very frequent (99-80%)

An abnormality of the nervous system.

Acanthocytosis · Very frequent (99-80%)

Acanthocytosis is a type of poikilocytosis characterized by the presence of spikes on the cell surface. The cells have an irregular shape resembling many-pointed stars.

Fat malabsorption · Very frequent (99-80%)

Abnormality of the absorption of fat from the gastrointestinal tract.

Low levels of vitamin E · Very frequent (99-80%)

A reduced concentration of vitamin E in the blood circulation. Vitamin E is a lipophilic vitamin that is also known as alpha-tocopherol.

Steatorrhea · Very frequent (99-80%)

Greater than normal amounts of fat in the feces. This is a result of malabsorption of lipids in the small intestine and results in frothy foul-smelling fecal matter that floats.

Abnormality of retinal pigmentation · Frequent (79-30%)

Any deviation from the normal pigmentation of the retina.

Anemia · Frequent (79-30%)

A reduction in erythrocytes volume or hemoglobin concentration.

Other findings in the same source

From: Orphanet

Additional reported features include Areflexia (Frequent (79-30%)); Chronic diarrhea (Frequent (79-30%)); Color vision defect (Frequent (79-30%)); Decreased HDL cholesterol concentration (Frequent (79-30%)); Decreased LDL cholesterol concentration (Frequent (79-30%)); Failure to thrive (Frequent (79-30%)); Hyperbilirubinemia (Frequent (79-30%)); Hypoalbuminemia (Frequent (79-30%)); Hypocholesterolemia (Frequent (79-30%)); Hypotriglyceridemia (Frequent (79-30%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Abetalipoproteinemia is Metabolic Medicine, with a metabolic specialist / clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with metabolic specialist / clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Is a biochemical or molecular result needed to clarify the diagnosis?
• Does this condition require an individual plan for illness or reduced food intake?
• Should nutrition advice come from a specialist metabolic dietitian?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Abetalipoproteinemia. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.