Progressive familial intrahepatic cholestasis type 5

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ORPHA:480476OMIM:617049K76.8
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Overview

Progressive familial intrahepatic cholestasis type 5 (PFIC5) is a rare inherited liver disease that affects how bile flows from the liver. Bile is a fluid made by the liver that helps digest fats and carries waste products out of the body. In PFIC5, a faulty gene causes bile to build up inside liver cells instead of flowing normally into the intestines. This buildup is toxic to liver cells and causes ongoing damage over time. PFIC5 is caused by changes (mutations) in the NR1H4 gene, which provides instructions for making a protein called FXR (farnesoid X receptor). FXR acts like a master switch that controls bile production and flow. When FXR does not work properly, the liver cannot regulate bile acids, leading to a dangerous buildup. PFIC5 is also sometimes called FXR deficiency or NR1H4-related cholestasis. The main symptoms include severe itching, yellowing of the skin and eyes (jaundice), poor growth, and liver failure that often begins in infancy or early childhood. The disease tends to be more aggressive than other PFIC types. Without treatment, most children with PFIC5 develop serious liver failure requiring a liver transplant. Management focuses on relieving symptoms, slowing liver damage, and in many cases, planning for liver transplantation. Research into targeted therapies is ongoing.

Also known as:

Key symptoms:

Severe, persistent itching all over the bodyYellowing of the skin and whites of the eyes (jaundice)Poor weight gain and slow growth in infants and childrenDark-colored urinePale or clay-colored stoolsSwollen belly due to fluid buildup (ascites)Fatigue and low energyBleeding or bruising easily due to poor vitamin K absorptionVitamin deficiencies (especially vitamins A, D, E, and K)Liver failure in infancy or early childhoodEnlarged liver and spleen

Inheritance

Autosomal recessive

Passed on when both parents carry the same gene change; often skips generations

Age of Onset

Infantile

Begins in infancy, roughly 1 month to 2 years old

Orphanet ↗OMIM ↗NORD ↗

Treatments

No FDA-approved treatments are currently listed for Progressive familial intrahepatic cholestasis type 5.

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No actively recruiting trials found for Progressive familial intrahepatic cholestasis type 5 at this time.

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No specialists are currently listed for Progressive familial intrahepatic cholestasis type 5.

View NORD Rare Disease Centers ↗Undiagnosed Disease Network ↗

Treatment Centers

8 centers
🏥 NORD

Baylor College of Medicine Rare Disease Center

Baylor College of Medicine

📍 Houston, TX

🏥 NORD

Stanford Medicine Rare Disease Center

Stanford Medicine

📍 Stanford, CA

🔬 UDN

NIH Clinical Center Undiagnosed Diseases Program

National Institutes of Health

📍 Bethesda, MD

🔬 UDN

UCLA UDN Clinical Site

UCLA Health

📍 Los Angeles, CA

🔬 UDN

Baylor College of Medicine UDN Clinical Site

Baylor College of Medicine

📍 Houston, TX

🔬 UDN

Harvard/MGH UDN Clinical Site

Massachusetts General Hospital

📍 Boston, MA

🏥 NORD

Mayo Clinic Center for Individualized Medicine

Mayo Clinic

📍 Rochester, MN

👤 Mayo Clinic Center for Individualized Medicine

🏥 NORD

UCLA Rare Disease Day Program

UCLA Health

📍 Los Angeles, CA

Travel Grants

No travel grants are currently matched to Progressive familial intrahepatic cholestasis type 5.

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Community

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Caregiver Resources

NORD Caregiver Resources

Support, advocacy, and financial assistance for caregivers of rare disease patients.

Mental Health Support

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Family & Caregiver Grants

Financial assistance programs specifically for caregivers of rare disease patients.

Social Security Disability

Learn how rare disease patients may qualify for SSDI/SSI benefits.

Questions for your doctor

Bring these to your next appointment

  • Q1.What stage is my child's liver disease at, and how quickly might it progress?,Is my child a candidate for liver transplantation, and when should we start planning for it?,Which medications and vitamin supplements does my child need, and how do I give them correctly?,Are there any clinical trials or new treatments for PFIC5 that my child might qualify for?,What signs should prompt me to go to the emergency room immediately?,Should other family members be tested for the NR1H4 gene mutation?,What dietary changes or special nutrition does my child need, and can we see a dietitian?

Common questions about Progressive familial intrahepatic cholestasis type 5

What is Progressive familial intrahepatic cholestasis type 5?

Progressive familial intrahepatic cholestasis type 5 (PFIC5) is a rare inherited liver disease that affects how bile flows from the liver. Bile is a fluid made by the liver that helps digest fats and carries waste products out of the body. In PFIC5, a faulty gene causes bile to build up inside liver cells instead of flowing normally into the intestines. This buildup is toxic to liver cells and causes ongoing damage over time. PFIC5 is caused by changes (mutations) in the NR1H4 gene, which provides instructions for making a protein called FXR (farnesoid X receptor). FXR acts like a master swit

How is Progressive familial intrahepatic cholestasis type 5 inherited?

Progressive familial intrahepatic cholestasis type 5 follows a autosomal recessive inheritance pattern. Genetic counseling can help families understand recurrence risk and testing options.

At what age does Progressive familial intrahepatic cholestasis type 5 typically begin?

Typical onset of Progressive familial intrahepatic cholestasis type 5 is infantile. Age of onset can vary across affected individuals.