Familial Dysbetalipoproteinemia

Familial Dysbetalipoproteinemia

Article
Vein & Vascular Health
Digestive Health
+4
Contributed byMaulik P. Purohit MD MPHSep 11, 2018

What are the other Names for this Condition? (Also known as/Synonyms)

  • Broad Beta Disease
  • Remnant Particle Removal Disease
  • Remnant Removal Disease

What is Familial Dysbetalipoproteinemia? (Definition/Background Information)

  • Familial Dysbetalipoproteinemia (FD) is a hereditary disorder characterized by high amounts of lipids (fat) in the body and blood. In this disorder, there is defective breakdown or metabolism of lipids
  • In blood, excess lipids (cholesterol and triglycerides) get laid down on the inner layer of the blood vessels (atherosclerosis), leading to narrowing of the blood vessel tube and finally leading to blockage. When an obstruction occurs in the blood vessels of the heart (coronary), it can cause chest pain and heart attacks
  • In the body, the lipids get deposited in the skin, underneath the skin (subcutaneous) and in the tendons. This is seen as multiple, soft yellow lipid-filled lumps on the skin (xanthomas) or tendons
  • Familial Dysbetalipoproteinemia is inherited in an autosomal recessive manner, which means that the individual inherits 2 defective genes (forming a gene pair) from each parent and the disease is manifested
  • Familial Dysbetalipoproteinemia has a favorable outcome, if there is an early diagnosis of the condition, which is followed by FD management measures such as lipid-lowering therapy and dietary and lifestyle modifications
  • Without treatment, the affected individuals have a 5 to 10  times higher risk of heart attacks, stroke, etc. than the general population

Who gets Familial Dysbetalipoproteinemia? (Age and Sex Distribution)

  • Familial Dysbetalipoproteinemia is a congenital genetic disorder and children are born with the disorder. However, typically the symptoms of the disorder are manifested only after a period of 20 years in males, and after menopause in females. Some studies reveal that it may present symptoms during childhood or in elderly adults too
  • Familial Dysbetalipoproteinemia is more common in men than in women, because estrogen in women has a protective effect. This protective effect wears-off after menopause
  • The condition can occur worldwide. The prevalence in general population is 1 in 5,000-10,000; it is also estimated to be present in 0.7-3% of different population groups

What are the Risk Factors for Familial Dysbetalipoproteinemia? (Predisposing Factors)

  • The major risk factor of Familial Dysbetalipoproteinemia is a positive family history of the disorder
  • The presence of obesity, diabetes mellitus, or hypothyroidism can worsen the disorder

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Familial Dysbetalipoproteinemia? (Etiology)

Familial Dysbetalipoproteinemia is a genetic condition that is inherited as an autosomal recessive trait.

  • Normally, apolipoprotein E (Apo E protein) transports lipids in blood and at the same time, clears them from blood
    • The genes of Apo E are available in various forms and are numbered e3, e3, and e4
    • e3” is the normal gene and its product (Apo E2) effectively transports lipids. The other forms are mutants (abnormal)
    • In Familial Dysbetalipoproteinemia, the mutant “e2” gene encodes Apo E2. Apo E2 does not effectively transport lipids, which leads to atherosclerosis and xanthoma formation          
  • Defective Apo E impairs the clearance of the fatty remnant particles and as a result, fatty-remnant particles accumulate and cause the symptoms
  • Generally, individuals with FD are at risk to become symptomatic, only when other risk factors, such as hypothyroidism, obesity, diabetes, increasing age, low estrogen states, and other unknown environmental factors, are associated with it
  • This condition can also be inherited in an autosomal dominant manner; but, it occurs very rarely. The defects in these individuals are due to mutations of genes other than “e3”. Such individuals are known to become symptomatic right after birth. In an autosomal dominant disorder, the individual inherits only one gene (1 of 2 genes in a pair) from an affected parent

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children, born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Familial Dysbetalipoproteinemia?

Most individuals are asymptomatic; the symptoms are usually observed into adulthood. The signs and symptoms of Familial Dysbetalipoproteinemia include:

  • Yellow, fatty, skin deposits, called xanthomas, appear on the eyelids (xanthelasma), palms, soles, finger digits, buttocks, or on the tendons of the knees, elbows, and ankles (Achilles tendon). Xanthomas in the palms is very specific to FD and is not seen in any other condition
  • Fatty deposits around the black of the eye (arcus lidus corneae)
  • Fatty deposits causing thickening of the arteries (atherosclerosis) occur at an early age. This can cause symptoms (usually before the age of 50 years), due to reduction in blood supply to the heart, limbs, or other parts of the body. In such cases, the symptoms may include:
    • Chest pain, shortness of breath, leg pain while walking, non-healing sores on the toes, paralysis, and weakness
    • Decreased pulse in the lower part of the body, due to decreased blood suppl   
  • High levels of triglycerides in blood can cause pancreatitis and present with symptoms such as back pain, abdominal pain, nausea and vomiting
  • Increase in liver and spleen size may be seen in some individuals

The signs and symptoms of associated conditions (which may have precipitated symptoms of FD), such as hypothyroidism, obesity, and diabetes mellitus type 2, may be present.

How is Familial Dysbetalipoproteinemia Diagnosed?

The following procedures may be used to diagnose Familial Dysbetalipoproteinemia (FD):

  • Thorough evaluation of the individual’s medical history and a complete physical examination
  • During history taking the healthcare provider may want to know the following:
    • About the presence of symptoms pertaining to the heart and arteries, when the symptoms began, and whether they are becoming worse
    • About one’s personal and family history of heart attacks, abnormal blood lipid levels, diabetes mellitus, obesity, etc.           
  • Blood tests that may be performed include lipid profile, which may indicate the following:
    • Elevated total cholesterol levels, typically ranging from 300-600 mg/dL
    • Elevated triglyceride (TG) levels, typically ranging from 400- 800 mg/dL
    • VLDL (very low density lipoprotein) levels are usually elevated in FD; specifically, the VLDL:TG ratio is characteristically increased
    • Low HDL cholesterol levels           
  • Electrophoresis is a test on a sample of blood or urine. It separates particles based on molecular size using electrical current. In FD, a characteristic” broad beta band” may be seen
  • Genotyping test is done from a sample of blood. It helps in finding the type of gene the individual has, which is e2, e3, or e4

    • “e3” is the normal apolipoprotein E gene
    • “e2” is the most common mutant gene found in individuals with Familial Dysbetalipoproteinemia
    • Types other than e2, e3, or e4 is found in very rare types of Familial Dysbetalipoproteinemia
  • Silent (asymptomatic) atherosclerosis may be demonstrated with carotid ultrasound test, which shows thickening of the inner lining of the blood vessel
  • Diagnostic tests to determine the overall health of the heart, such as stress test and angiogram, may be performed depending on the clinical situation
  • Diagnostic testing of associated conditions, such as type 2diabetes mellitus, obesity, hypothyroidism, etc. may also be undertaken in these individuals

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Familial Dysbetalipoproteinemia?

The complications of Familial Dysbetalipoproteinemia could include:

  • Early heart attack due to premature cardiovascular disease
  • Transient stroke or stroke
  • Peripheral vascular diseases (PVD) are diseases due to decreased blood supply to regions of the body other than the heart and brain. PVD symptoms, such as pain on walking (claudication) and gangrene (death of tissue), are most commonly seen in the lower extremities
  • Pancreatitis may be seen in individuals with triglyceride levels more than 1000 mg/dL

How is Familial Dysbetalipoproteinemia Treated?

Individuals with Familial Dysbetalipoproteinemia are at risk of becoming symptomatic usually only when other risk factors, such as hypothyroidism, obesity, diabetes, increasing age, low estrogen states, and other unknown environmental factors, are associated with it. Treating these conditions is a key aspect of FD treatment.

Familial Dysbetalipoproteinemia is initially treated by dietary and lifestyle modifications, which may include:

  • Consultation with dietitians and nutrition experts to devise a dietary plan
  • Decreased consumption of saturated fat; reducing total fat intake to less than 30% of the total calories
  • Completely avoiding consumption of trans fat present in packaged foods
  • Limiting the amount of cholesterol consumption
  • Decreasing the consumption of sugars
  • Regular exercise or increased physical activity (with at least 30 minutes of physical activity 4 days per week)
  • Enrolling in weight loss programs if one is obese or overweight
  • Smoking cessation 
  • Limiting the amount of alcohol consumption

If cholesterol and triglyceride levels remain elevated, despite dietary and lifestyle modification, then additionally, the following lipid lowering medications may be administered:

  • Bile acid-sequestering agents
  • Gemfibrozil
  • Fenofibrate
  • Clofibrate
  • Nicotinic acid
  • Statins
  • Estrogen therapy in postmenopausal women

Xanthomas can be prevented from occurring, if hyperlipidemia is diagnosed and controlled early in the course of the disorder. However, if the individual has xanthomas before treatment for hyperlipidemia, it usually does not appear on its own; in such conditions, a surgical removal may be necessary.

How can Familial Dysbetalipoproteinemia be Prevented?

  • Currently, there are no specific methods or guidelines to prevent Familial Dysbetalipoproteinemia, since it is a genetic condition
  • Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
  • If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
  • Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Nevertheless, the following measures may be taken to decrease the risk of heart disease, peripheral vascular disease, and other associated conditions in the affected individuals and their family members:

  • In individuals diagnosed with FD, avoiding or controlling the risk factors, such as smoking, obesity, and a sedentary lifestyle, helps in preventing early heart attacks and strokes
  • Dietary modifications, such as avoiding saturated and trans fat, and reduction in the intake of calories
  • Early blood lipid screening of family members including children of the affected individuals

What is the Prognosis of Familial Dysbetalipoproteinemia? (Outcomes/Resolutions)

  • Familial Dysbetalipoproteinemia can increase the risk of early heart attacks and strokes. If lipid-lowering therapy, dietary modifications, and/or lifestyle modifications are undertaken, then there is a favorable outcome. Most individuals show a large reduction (dramatic improvement) in lipid levels with treatment
  • If FD and its associated risk factors are not diagnosed and treated properly, then the outcome is guarded. These individuals have a very risk of heart attacks or strokes; almost 5-10 times higher risk than individuals of the general population

Additional and Relevant Useful Information for Familial Dysbetalipoproteinemia:

The following DoveMed website link is a useful resource for additional information:

https://www.dovemed.com/diseases-conditions/congenital-genetic-disorders/

Was this article helpful

On the Article

Maulik P. Purohit MD MPH picture
Approved by

Maulik P. Purohit MD MPH

Assistant Medical Director, Medical Editorial Board, DoveMed Team

0 Comments

Please log in to post a comment.

Related Articles

Test Your Knowledge

Asked by users

Related Centers

Loading

Related Specialties

Loading card

Related Physicians

Related Procedures

Related Resources

Join DoveHubs

and connect with fellow professionals

Related Directories

Who we are

At DoveMed, our utmost priority is your well-being. We are an online medical resource dedicated to providing you with accurate and up-to-date information on a wide range of medical topics. But we're more than just an information hub - we genuinely care about your health journey. That's why we offer a variety of products tailored for both healthcare consumers and professionals, because we believe in empowering everyone involved in the care process.
Our mission is to create a user-friendly healthcare technology portal that helps you make better decisions about your overall health and well-being. We understand that navigating the complexities of healthcare can be overwhelming, so we strive to be a reliable and compassionate companion on your path to wellness.
As an impartial and trusted online resource, we connect healthcare seekers, physicians, and hospitals in a marketplace that promotes a higher quality, easy-to-use healthcare experience. You can trust that our content is unbiased and impartial, as it is trusted by physicians, researchers, and university professors around the globe. Importantly, we are not influenced or owned by any pharmaceutical, medical, or media companies. At DoveMed, we are a group of passionate individuals who deeply care about improving health and wellness for people everywhere. Your well-being is at the heart of everything we do.

© 2023 DoveMed. All rights reserved. It is not the intention of DoveMed to provide specific medical advice. DoveMed urges its users to consult a qualified healthcare professional for diagnosis and answers to their personal medical questions. Always call 911 (or your local emergency number) if you have a medical emergency!