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

• MDR3 Deficiency Disorder
• PFIC3 (Progressive Familial Intrahepatic Cholestasis Type 3)
• Progressive Familial Intrahepatic Cholestasis with Elevated Serum Gamma-Glutamyltransferase

What is Progressive Familial Intrahepatic Cholestasis Type 3? (Definition/Background Information)

• Progressive Familial Intrahepatic Cholestasis Type 3 (PFIC3) is a rare condition that affects the liver
• People with this condition generally develop signs and symptoms during late infancy or early childhood, which may include severe itching, jaundice, failure to thrive, portal hypertension (high blood pressure in the vein that provides blood to the liver) and hepatosplenomegaly (enlarged liver and spleen)
• The condition may progress to liver failure during childhood or adulthood
• PFIC3 is caused by change (mutations) in the ABCB4 gene and is inherited in an autosomal recessive manner
• Treatment may include ursodeoxycholic acid therapy to prevent liver damage, surgery and/or liver transplantation

(Source: Progressive Familial Intrahepatic Cholestasis Type 3; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets Progressive Familial Intrahepatic Cholestasis Type 3? (Age and Sex Distribution)

• Progressive Familial Intrahepatic Cholestasis Type 3 is a rare congenital disorder. The presentation of symptoms may occur after birth - in infants or very young children
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Progressive Familial Intrahepatic Cholestasis Type 3? (Predisposing Factors)

• A positive family history may be an important risk factor, since Progressive Familial Intrahepatic Cholestasis Type 3 can be inherited
• Currently, no other risk factors have been clearly identified for PFIC3

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s 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 Progressive Familial Intrahepatic Cholestasis Type 3? (Etiology)

• The condition is inherited in an autosomal recessive manner

(Source: Progressive Familial Intrahepatic Cholestasis Type 3; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

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 Progressive Familial Intrahepatic Cholestasis Type 3?

The signs and symptoms of Progressive Familial Intrahepatic Cholestasis Type 3 may include:

• Cirrhosis
• Diarrhea
• Bile duct proliferation
• Elevated hepatic transaminases
• Hepatomegaly
• Intrahepatic cholestasis
• Jaundice
• Malabsorption
• Pruritus
• Portal fibrosis

(Source: Progressive Familial Intrahepatic Cholestasis Type 3; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Progressive Familial Intrahepatic Cholestasis Type 3 Diagnosed?

Progressive Familial Intrahepatic Cholestasis Type 3 is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary

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 Progressive Familial Intrahepatic Cholestasis Type 3?

The complications of Progressive Familial Intrahepatic Cholestasis Type 3 may include:

• Liver failure
• Complications following liver transplant

How is Progressive Familial Intrahepatic Cholestasis Type 3 Treated?

• The treatment for Progressive Familial Intrahepatic Cholestasis Type 3 may include ursodeoxycholic acid therapy to prevent liver damage, surgery and/or liver transplantation

(Source: Progressive Familial Intrahepatic Cholestasis Type 3; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How can Progressive Familial Intrahepatic Cholestasis Type 3 be Prevented?

Currently, Progressive Familial Intrahepatic Cholestasis Type 3 may not be preventable, since it is a genetic disorder.

• 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

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Progressive Familial Intrahepatic Cholestasis Type 3? (Outcomes/Rresolutions)

• The prognosis of Progressive Familial Intrahepatic Cholestasis Type 3 is dependent upon the severity of the signs and symptoms and associated complications, if any
• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Progressive Familial Intrahepatic Cholestasis Type 3:

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

http://www.dovemed.com/diseases-conditions/rare-disorders/