What is Abetalipoproteinemia?
Abetalipoproteinemia, often referred to as ABL, is an uncommon genetic disorder where a person has extremely low or even non-existent levels of certain types of fats in their blood, specifically plasma cholesterol, low-density lipoproteins (LDLs), and very-low-density lipoproteins (VLDLs). It’s important not to mistake this condition for a shortage of beta-lipoproteins, as they are not the same thing. The main symptoms of ABL are difficulty absorbing fat, degeneration of the spinal cord and cerebellum (a part of the brain), abnormal red blood cells, and eye disease called retinitis pigmentosa.
The goal of treatment for ABL is to stop the nerve damage and prevent complications caused by problems with nutrient absorption in the patients.
What Causes Abetalipoproteinemia?
Abetalipoproteinemia is a condition that happens because of a particular mutation in the MTTP gene. This gene is involved in creating a component called microsomal triglyceride protein (MTP) which helps with the assembly and transport of certain fats in our body’s cells. Currently, more than 33 distinct mutations that bring about this disease have been identified.
Most of the symptoms of abetalipoproteinemia come from a severe shortage of fats and vitamins in the body that are usually absorbed from food, especially Vitamin E. This shortage can lead to several health issues. For example, babies with this condition often struggle to grow and put on weight, might have fatty, foul-smelling stools and could have a swollen belly. They might also develop more serious problems like a certain type of nerve damage known as spinocerebellar degeneration and an eye condition called retinitis pigmentosa.
Risk Factors and Frequency for Abetalipoproteinemia
Abetalipoproteinemia is a rare condition, affecting less than 1 in a million people, and is often linked to marriages between close relatives. This disease is autosomal recessive, meaning that both copies of the gene need to be defective for a person to develop the condition. It can affect both men and women equally.
People of Ashkenazi Jewish descent, primarily from eastern and central Europe, frequently have a specific mutation. This mutation involves a change in a single protein building block, or amino acid. Normally, this position should contain the amino acid glycine, but the mutation replaces it with a ‘stop’ signal, which is known as Gly865X or G865X. This change results in the production of a smaller, non-functioning version of the protein.
Signs and Symptoms of Abetalipoproteinemia
Failure to thrive in infancy can lead to various symptoms, which can be grouped into three categories: gastroenterology symptoms, neurologic symptoms, and ophthalmologic symptoms.
Gastroenterologic symptoms may include:
- Fatty, loose stools (steatorrhea) and diarrhea
- Swellings in the belly (abdominal distension)
Neurologic symptoms can manifest as:
- Slow mental development
- Lack of deep tendon reflexes
- Loss of coordination (ataxia)
- Slurred speech
- Damage to peripheral nerves (Peripheral neuropathy)
- Tremors that occur during targeted movements (Intention tremors)
Ophthalmologic symptoms, related to eye health, include:
- Eye disease by adolescence known as Retinitis pigmentosa (caused by Vitamin A deficiency)
- Decreased ability to see at night or distinguish colors
- Potential blindness
Testing for Abetalipoproteinemia
A complete blood count is a test that can show issues such as anemia, low platelet count, or a general reduction in all types of blood cells.
A blood smear is another test that doctors may use, which involves looking at your blood under a microscope. This test can help find specific types of abnormal cells called acanthocytes, or Burr cells.
A fasting lipid profile is a test that measures the fat in your blood after you have not eaten for a certain period. This test can show low levels of certain types of fats, like VLDLs, LDLs, and total cholesterol.
Stool studies involve testing a sample of your stool in a laboratory. In this case, these tests can show if your body is not properly absorbing fat, and helps rule out other potential causes.
There are also images studies that doctors can use to diagnose certain health conditions. For instance, a hepatic scan or ultrasound can look at changes in the liver that might be caused by excess fat.
A magnetic resonance imaging (MRI) scan of the spinocerebellar region, which is part of the brain, can help detect degeneration.
Doctors can also conduct an eye and retinal examination and imaging to check for any damage to the retina, which is the layer of tissue at the back of the inner eye that processes light.
Treatment Options for Abetalipoproteinemia
The treatment strategy for this condition involves a careful alteration of a person’s diet and the inclusion of certain supplements. This includes a very firm limitation on the intake of long-chain fatty acids.
It also involves taking specific vitamins. High doses of vitamin E are often taken orally. Additionally, if an individual’s prothrombin time – a measure of how quickly blood clots – is elevated, they may need to take vitamin A. This is because a high prothrombin time can suggest that the body’s stores of vitamin K have been depleted.
In addition to these dietary changes and supplements, additional treatments like physiotherapy and occupational therapy may be needed. These therapies can help manage the symptoms and improve the individual’s overall wellbeing.
What else can Abetalipoproteinemia be?
- Long-term liver disease characterized by impaired bile flow
- Combined nerve damage and loss of balance or coordination
- Family-related vitamin E deficiency
- Inherited nerve diseases affecting sense of touch and movement
- Deterioration of the retina in the eye
- Secondary cancers (cancer that originated elsewhere and spread)
- Disorders that damage the spinal cord and cerebellum, affecting balance and muscle coordination
What to expect with Abetalipoproteinemia
The chances of a patient with abetalipoproteinemia getting better depend on several factors:
* The age of the patient when the diagnosis was made
* The start of treatment with a low-fat diet and vitamin replacement therapy
* The specific type of mutation in the MTP gene and APOE gene that the patient has
These things play a significant role in predicting the patient’s long-term outcome.