ATP8B1, ABCB11, ABCB4, TJP2, NR1H4 and MYO5B genes

Also known as: PFIC1 or Byler disease, PFIC2, PFIC3, MDR3 deficiency or Progressive familial intrahepatic cholestasis, with elevated serum gamma-glutamyltransferase; PFIC4; PFIC5; PFIC6








1. The disease

Progressive familial intrahepatic cholestasis is a rare, heterogeneous group of liver disorders of autosomal recessive inheritance, characterised by an early onset of cholestasis with pruritus and malabsorption, which rapidly progresses, eventually culminating in liver failure.

2. The symptoms

Patients with the most common forms of PFIC (PFIC1 and PFIC2) generally present with jaundice and severe pruritus in the first few months of life.

Significant pruritus can lead to severe cutaneous mutilation and may affect many activities of daily living through loss of sleep, irritability, poor attention, and impaired school performance. Lack of early signs or symptoms does not exclude the diagnosis.

3. Actions to take in case of early diagnosis

  • Infants with a positive genetic test (having 2 pathogenic variants or 2 copies of a single pathogenic variant in UGT1A1 gene) should continue breastfeeding. Early treatment can save lives.
  • PFIC is a life-threatening condition that requires lifetime management and regular follow-up with a paediatric gastroenterologist physician, dietician, and a multidisciplinary approach to care.
  • Nutritional management is the first step, being necessary to change the formula to a specialised one to maintain growth and manage malabsorption.
  • The focus of pharmacological treatment is to relieve pruritus which is the most distressing symptom in PFIC.
  • Other aims are to slow the disease progression, to improve the nutritional status, to correct vitamin deficiencies, and to treat the complications of advanced liver disease such as ascites and variceal bleeding.
  • Liver transplant is indicated if there is hepatic insufficiency.
  • Genetic counselling is highly recommended for family planning and evaluation of at-risk family members such as siblings.

4. For more information

Biblio: Jones-Hughes, T., Campbell, J., & Crathorne, L. (2021). Epidemiology and burden of progressive familial intrahepatic cholestasis: a systematic review. Orphanet journal of rare diseases16(1), 255.