Progressive familial intrahepatic cholestasis type 2

What else is it called?

  • PFIC2  
  • Severe ABCB11 deficiency  
  • BSEP deficiency  
  • Byler syndrome 

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What causes it?

This disorder is caused by a problem in ABCB11 gene. This gene provides instructions for the protein known as the bile salt export pump (BSEP). The bile salt export pump is responsible for secreting the liquid known as bile which helps in digestion. If you have a problem with the ABCB11 gene then you will not produce enough of the BSEP protein therefore there will be a decreased flow of bile acid which exposes your liver cells to bile salt accumulation because of the build-up of liver in the liver which results in the increased liver cell damage which ultimately causes type two progressive familial intrahepatic cholestasis. 

How common is it?

The estimated prevalence of progressive familial intrahepatic cholestasis at birth varies between 1:50,000 and 1:100,000 and type two progressive familial intrahepatic cholestasis represents half of the progressive familial intrahepatic cholestasis cases. However, both sexes are affected equally by progressive familial intrahepatic cholestasis. The estimated prevalence in the population of the United Kingdom is 10-15% This disorder is much more common in the Inuit population of Greenland and the old order Amish population in the united states. 

What are the signs and symptoms?

Symptoms usually present during infancy and the symptoms are:  

  • Diarrhoea 
  • Failure to thrive (Faltering weight) 
  • Jaundice (yellow skin)  
  • Pruritus (itching)  
  • Hepatomegaly (increased liver size) 
  • Splenomegaly (increased spleen size)  
  • Cirrhosis  

Type two Progressive familial intrahepatic cholestasis is a progressive disease, it usually progresses to liver failure within a child’s first few years of life. in addition, there is an increased risk that affected people will develop hepatocellular carcinoma and eventually death.

How is it diagnosed?

Type two Progressive familial intrahepatic cholestasis is not yet screened for in the United Kingdom and the united states. Type two progressive familial intrahepatic cholestasis is diagnosed by liver ultrasonography, BSEP immunostaining, biliary lipid analysis, liver histology and genotyping. However, genotyping confirms the diagnosis. There is differential diagnosis for this disease, and these are: primary bile acid synthesis defects and type one progressive familial intrahepatic cholestasis. Biliary lipid analysis reveals the decreased amount of biliary bile salt concentrations which is an indication of the disease.  

 

Can it be treated?

Type two Progressive familial intrahepatic cholestasis can be managed using ursodeoxycholic acid therapy (UDCA), cholestyramine, surgical biliary diversion and nasobiliary drainage. If all these therapies fail, then the only alternative will be a liver transplantation. 

The prognosis of this disorder is that children diagnosed with progressive familial intrahepatic cholestasis are at risk of the disorder progressing further to biliary stones, drug induced cholestasis and intrahepatic cholestasis of pregnancy (ICP). This disorder has a number of complications that are associated with it, which are: portal hypertension, liver failure, cirrhosis, hepatocellular carcinoma, cholangiocarcinoma and extrahepatic manifestations for example diarrhoea. 

Do my family need to be tested?

Type two progressive familial intrahepatic cholestasis is an autosomal recessive inherited metabolic disorder. Humans are composed of DNA and DNA is composed of chromosomes. Genes are sections of DNA which provide genetic instructions. Humans are made up of 46 chromosomes and we inherit 23 chromosomes from your mother and 23 chromosomes from your father which combine to produce instructions to make a human.  

Everyone as a pair of genes which are needed in order to produce the Bile salt export pump. When both these genes are not working correctly type two progressive intrahepatic cholestasis forms. For a child to develop type two progressive intrahepatic cholestasis they need to need to inherit two of the defective ABCB11 genes from their parents, the parents do not need to be diagnosed with type two progressive intrahepatic cholestasis. They merely need to be carriers of type two progressive intrahepatic cholestasis. A carrier is someone who only has one defective gene in the pair, but they do not have the disorder because the other gene is working perfectly.  

In the event that both of the parents are carriers of type two progressive intrahepatic cholestasis. There is a: 

  • 25% chance that one of the children will be unaffected by type two progressive intrahepatic cholestasis and will not be a carrier. 
  • 25% chance that the child will inherit type two progressive intrahepatic cholestasis.  
  • 50% chance that the child will be unaffected by type two progressive intrahepatic cholestasis and will be a carrier.     

Relevant Organisations

References

References are available on request. Please contact Helen Morris by phoning 0845 241 2173 or emailing helen@metabolicsupportuk.org [Resource Library No: AAP002]. 

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