SIGN IN YOUR ACCOUNT TO HAVE ACCESS TO DIFFERENT FEATURES

FORGOT YOUR PASSWORD?

FORGOT YOUR DETAILS?

AAH, WAIT, I REMEMBER NOW!
24/7 HELPLINE (903) 212-7500
  • PATIENT PORTAL LOGIN

PhyNet Health PhyNet Health

  • Home
  • Find a Clinic
    • Hughes Springs, TX
    • Longview, TX
    • Jefferson, TX
    • Kilgore, TX
    • Lindale, TX
    • Linden, TX
    • Gladewater, TX
    • Lone Star, TX
    • Tatum, TX
    • Marshall, TX
  • Health Services
    • Primary Care Services
    • Physical Therapy / Rehab
    • Allergy Testing & Treatment
    • Chronic Care Management
    • Remote Monitoring Program
    • Virtual Visit
  • Resources
    • MedlinePlus Wiki
      • Health Topics
    • Home Health Coordination
    • Transitions of Care
    • Insurance Help
  • About Phynet
    • About Phynet
    • PhyNet News
    • Better Together Stories
    • Careers
  • Billing

Health Topics

Skip navigation

An official website of the United States government

Here’s how you know

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS
A lock ( Lock Locked padlock icon ) or https:// means you’ve safely connected to the .gov website. Share sensitive information only on official, secure websites.

National Institutes of Health National Library of Medicine
MedlinePlus Trusted Health Information for You
  • Health Topics
  • Drugs & Supplements
  • Genetics
  • Medical Tests
  • Medical Encyclopedia
  • About MedlinePlus
  • About MedlinePlus
  • What's New
  • Site Map
  • Customer Support
  • Health Topics
  • Drugs & Supplements
  • Genetics
  • Medical Tests
  • Medical Encyclopedia
You Are Here:
Home →
Genetics →
Genetic Conditions →
Progressive familial intrahepatic cholestasis
URL of this page: https://medlineplus.gov/genetics/condition/progressive-familial-intrahepatic-cholestasis/

Progressive familial intrahepatic cholestasis

Description

Progressive familial intrahepatic cholestasis (PFIC) is a disorder that causes progressive liver disease, which typically leads to liver failure. In people with PFIC, liver cells are less able to secrete a digestive fluid called bile. The buildup of bile in liver cells causes liver disease in affected individuals.

Signs and symptoms of PFIC typically begin in infancy and are related to bile buildup and liver disease. Specifically, affected individuals experience severe itching, yellowing of the skin and whites of the eyes (jaundice), failure to gain weight and grow at the expected rate (failure to thrive), high blood pressure in the vein that supplies blood to the liver (portal hypertension), and an enlarged liver and spleen (hepatosplenomegaly).

There are three known types of PFIC: PFIC1, PFIC2, and PFIC3. The types are also sometimes described as shortages of particular proteins needed for normal liver function. Each type has a different genetic cause.

In addition to signs and symptoms related to liver disease, people with PFIC1 may have short stature, deafness, diarrhea, inflammation of the pancreas (pancreatitis), and low levels of fat-soluble vitamins (vitamins A, D, E, and K) in the blood. Affected individuals typically develop liver failure before adulthood.

The signs and symptoms of PFIC2 are typically related to liver disease only; however, these signs and symptoms tend to be more severe than those experienced by people with PFIC1. People with PFIC2 often develop liver failure within the first few years of life. Additionally, affected individuals are at increased risk of developing a type of liver cancer called hepatocellular carcinoma.

Most people with PFIC3 have signs and symptoms related to liver disease only. Signs and symptoms of PFIC3 usually do not appear until later in infancy or early childhood; rarely, people are diagnosed in early adulthood. Liver failure can occur in childhood or adulthood in people with PFIC3.

Frequency

PFIC is estimated to affect 1 in 50,000 to 100,000 people worldwide. PFIC type 1 is much more common in the Inuit population of Greenland and the Old Order Amish population of the United States.

Causes

Mutations in the ATP8B1, ABCB11, and ABCB4 genes can cause PFIC.

ATP8B1 gene mutations cause PFIC1. The ATP8B1 gene provides instructions for making a protein that helps to maintain an appropriate balance of bile acids, a component of bile. This process, known as bile acid homeostasis, is critical for the normal secretion of bile and the proper functioning of liver cells. In its role in maintaining bile acid homeostasis, some researchers believe that the ATP8B1 protein is involved in moving certain fats across cell membranes. Mutations in the ATP8B1 gene result in the buildup of bile acids in liver cells, damaging these cells and causing liver disease. The ATP8B1 protein is found throughout the body, but it is unclear how a lack of this protein causes short stature, deafness, and other signs and symptoms of PFIC1.

Mutations in the ABCB11 gene are responsible for PFIC2. The ABCB11 gene provides instructions for making a protein called the bile salt export pump (BSEP). This protein is found in the liver, and its main role is to move bile salts (a component of bile) out of liver cells. Mutations in the ABCB11 gene result in the buildup of bile salts in liver cells, damaging these cells and causing liver disease.

ABCB4 gene mutations cause PFIC3. The ABCB4 gene provides instructions for making a protein that moves certain fats called phospholipids across cell membranes. Outside liver cells, phospholipids attach (bind) to bile acids. Large amounts of bile acids can be toxic when they are not bound to phospholipids. Mutations in the ABCB4 gene lead to a lack of phospholipids available to bind to bile acids. A buildup of free bile acids damages liver cells and leads to liver disease.

Some people with PFIC do not have a mutation in the ATP8B1, ABCB11, or ABCB4 gene. In these cases, the cause of the condition is unknown.

Learn more about the genes associated with Progressive familial intrahepatic cholestasis

  • ABCB11
  • ABCB4
  • ATP8B1

Inheritance

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.

Other Names for This Condition

  • ABCB11-related intrahepatic cholestasis
  • ABCB4-related intrahepatic cholestasis
  • ATP8B1-related intrahepatic cholestasis
  • BSEP deficiency
  • Byler disease
  • Byler syndrome
  • FIC1 deficiency
  • Low γ-GT familial intrahepatic cholestasis
  • MDR3 deficiency

Additional Information & Resources

Genetic Testing Information

  • Genetic Testing Registry: Progressive familial intrahepatic cholestasis type 2 From the National Institutes of Health
  • Genetic Testing Registry: Progressive familial intrahepatic cholestasis type 3 From the National Institutes of Health
  • Genetic Testing Registry: Progressive familial intrahepatic cholestasis From the National Institutes of Health

Genetic and Rare Diseases Information Center

  • Progressive familial intrahepatic cholestasis type 2 From the National Institutes of Health
  • Progressive familial intrahepatic cholestasis type 3 From the National Institutes of Health

Patient Support and Advocacy Resources

  • National Organization for Rare Disorders (NORD)

Clinical Trials

  • ClinicalTrials.gov From the National Institutes of Health

Catalog of Genes and Diseases from OMIM

  • CHOLESTASIS, PROGRESSIVE FAMILIAL INTRAHEPATIC, 2; PFIC2
  • CHOLESTASIS, PROGRESSIVE FAMILIAL INTRAHEPATIC, 1; PFIC1
  • CHOLESTASIS, PROGRESSIVE FAMILIAL INTRAHEPATIC, 3; PFIC3

Scientific Articles on PubMed

  • PubMed From the National Institutes of Health

References

  • Alissa FT, Jaffe R, Shneider BL. Update on progressive familial intrahepatic cholestasis. J Pediatr Gastroenterol Nutr. 2008 Mar;46(3):241-52. doi: 10.1097/MPG.0b013e3181596060. Citation on PubMed
  • Bull LN, Morotti R, Squires JE. ATP8B1 Deficiency. 2001 Oct 15 [updated 2021 Sep 9]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Available from http://www.ncbi.nlm.nih.gov/books/NBK1297/ Citation on PubMed
  • Davit-Spraul A, Gonzales E, Baussan C, Jacquemin E. Progressive familial intrahepatic cholestasis. Orphanet J Rare Dis. 2009 Jan 8;4:1. doi: 10.1186/1750-1172-4-1. Citation on PubMed or Free article on PubMed Central
  • Harris MJ, Le Couteur DG, Arias IM. Progressive familial intrahepatic cholestasis: genetic disorders of biliary transporters. J Gastroenterol Hepatol. 2005 Jun;20(6):807-17. doi: 10.1111/j.1440-1746.2005.03743.x. Citation on PubMed
  • Jansen PL, Sturm E. Genetic cholestasis, causes and consequences for hepatobiliary transport. Liver Int. 2003 Oct;23(5):315-22. doi: 10.1034/j.1478-3231.2003.00856.x. Citation on PubMed
  • Pauli-Magnus C, Stieger B, Meier Y, Kullak-Ublick GA, Meier PJ. Enterohepatic transport of bile salts and genetics of cholestasis. J Hepatol. 2005 Aug;43(2):342-57. doi: 10.1016/j.jhep.2005.03.017. No abstract available. Citation on PubMed
Enlarge image

Related Health Topics

  • Bile Duct Diseases
  • Genetic Disorders
  • Jaundice
  • Liver Diseases

MEDICAL ENCYCLOPEDIA

  • Cholestasis
  • Genetics
  • Liver cancer - hepatocellular carcinoma

Understanding Genetics

  • What is the prognosis of a genetic condition?
  • How can gene variants affect health and development?
  • What does it mean if a disorder seems to run in my family?
  • What are the different ways a genetic condition can be inherited?
  • How are genetic conditions treated or managed?

Disclaimers

MedlinePlus links to health information from the National Institutes of Health and other federal government agencies. MedlinePlus also links to health information from non-government Web sites. See our disclaimer about external links and our quality guidelines.

The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.

  • About MedlinePlus
  • What's New
  • Site Map
  • Customer Support
  • Subscribe to RSSRSS
  • Connect with NLM
  • NLM Web Policies
  • Copyright
  • Accessibility
  • Guidelines for Links
  • Viewers & Players
  • HHS Vulnerability Disclosure
  • MedlinePlus Connect for EHRs
  • For Developers
National Library of Medicine 8600 Rockville Pike, Bethesda, MD 20894 U.S. Department of Health and Human Services National Institutes of Health
Last updated December 1, 2009
Return to top

Patients

  • Find a Clinic
  • Health Services
  • Complex Case Management
  • MA / Medicare Assistance

Quick Links

  • Billing Information
  • Careers
  • About Phynet
  • PhyNet News

Network Links

  • PrimeCareHomeHealth.com
  • PrimeCareNet.com
  • PrimeCareManagers.com
  • Core-Rehab.com

Home Office

4002 Technology Center Longview TX 75605
Phone: (903) 247-0484
Fax: (903) 247-0485
[email protected]
  • PrimeCareHomeHealth.com
  • PrimeCareNet.com
  • PrimeCareManagers.com
  • Core-Rehab.com
  • GET SOCIAL

© 2021 PhyNet Health • All rights reserved
YOUR LIFE. YOUR CHOICE.

TOP