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Byler's Disease
Thursday, 05 August 2004
Tuesday, 23 November 2004
Progressive Familial Intrahepatic Cholestasis

What

Byler’s Disease, which is now know as Progressive Familial Intrahepatic Cholestasis (PFIC), is a rare, inherited condition that mainly affects the liver and bile. Bile is made within the liver and is essential for the digestion and absorption of fats. Bile is transported from the liver to the small intestine through bile ducts. Children who suffer from PFIC are unable to drain bile from the liver even though the bile duct appears to be open and functional. Bile will then build up in the liver causing damage to liver cells. Over time, the liver damage can results in cirrhosis and liver failure. This usually occurs in the first decade of life and a liver transplant is usually necessary.

Who

PFIC is an extremely rare disease that seems to affect only children. Both boys and girls seem to be affected equally. The incidence and prevalence in children is not known because the disease is very rare. First described as Byler’s disease, this disease was thought to only occur in descendants of an Amish man named Jacob Byler. However, recently more cases have been reported and thus the change in the name of the disease to PFIC.

Signs and Symptoms

PFIC usually occurs soon after birth (within six months) and is a very rapidly progressing disease. Sometimes children may not develop the disease until later in childhood and even into adolescence. Children with PFIC may exihibit some or all of the following:

  • jaundice (yellowing of skin and/or eyes) – usually present soon after birth.
  • severe itching (pruritis) due to bile build up in skin
  • poor weight gain and/or growth (failure to thrive)
  • enlarged liver and/or enlarged spleen
  • lack of energy
  • loss of appetite with nausea and vomiting
  • foul smelling stools or fatty stools from the inability to absorp fat in the diet
  • pale, grey stools – from bile dysfunction
  • dark urine – excessive bilirubin in the urine.

Possible Causes

PFIC is a genetic disorder that is caused by a problem in the genes that code for the machinery needed to make bile and transport it from the liver into bile ducts. When this machinery fails, the liver cannot remove bile from the blood and eliminate it into the bile ducts. Bile is used for the excretion of toxins from the body and also the digestion of fats and vitamins. This will result in the build up of bile and toxins in the liver, bloodstream, and other places in the body like the skin. Liver damage can result from this blockage that can lead to liver failure. Furthermore, because bile is used for fat and vitamin digestion and absorption, a person may have fat and vitamin deficiencies that can inhibit proper growth and nutrition. A gene for PFIC has been identified and follows the inheritance pattern of autosomal recessive. Every person is born with two copies of every gene, one inherited from each parent. In order to have PFIC, a child must receive two bad copies of the PFIC gene. If the child only has one, then he/she will not be affected but is called a “carrier” for PFIC (and can pass this gene to their children). If both parents have one copy of the bad PFIC gene (both parents are carriers), then there is a 25% chance that their child will have PFIC, a 50% chance that the child will be a carrier, and a 25% chance that the child will have no bad PFIC genes.

Diagnosis

PFIC is diagnosed by recognition of the signs of liver dysfunction and through blood tests. Liver function tests and blood analysis are performed to assess the liver and biliary system. Children with PFIC will have high amounts of bile in their bloodstream. If the blood tests show that there is a problem with bile drainage, a special picture of the liver may be taken to see how much bile is flowing in the liver. A test called a bile salt screen may be used to confirm PFIC (PFIC patients have a very high bile salt content). Another test also used to differentiate between two types of PFIC is to test for the amount of an enzyme called gamma-glutamyl-transferase (GGT). A child may be diagnosed with one type of PFIC (Low-GGT PFIC) where the amount of GGT is normal or low in the blood, but bile levels are very high. Another type of PFIC (High-GGT PFIC) occurs when bile and GGT levels in the blood are very high. These children seem to have a more severe and progressive disease. Special DNA based genetic blood tests can be sent to confirm the diagnosis.

Treatment

The treatment of PFIC involves management of the symptoms of the disease, preventing any further complications, and surgical intervention. Depending on the severity of the disease, the primary intervention is to give medicines that will increase bile flow and relieve the severe itching due to build up of bile in the blood and skin. Vitamin supplements are needed because reduced bile leads to difficulties in absorption of vitamins A, D, E, and K. As the disease progresses, surgical intervention is the only option for patients with PFIC. A procedure called partial external biliary diversion (PEBD) is often first attempted to try to reduce the amount of bile circulating in the liver. This strategy is used to try to preserve the function of the liver and reduce liver damage. This surgical technique involves taking a piece of the intestine and using it as a channel for bile flow. The piece of intestine forms a passage form the gallbladder (organ that stores bile) to the outside of the skin thereby allowing the excretion of bile and wastes. PEBD is often used in older patients who are unresponsive to medical treatments. If the PEBD is unsuccessful or if PFIC progresses to end-stage liver failure, liver transplantation is the only curative option.

Prognosis

Most PFIC patients will progress to cirrhosis and will need a liver transplant at some point in their life. However the survival rates for liver transplantation are excellent with almost 90% of patients having successful transplants. There is a good quality of life after recovery from transplantation but close monitoring and lifetime immunosuppressive medications are required.

Connect with other parents

In the spirit of community and support, Madisons Foundation offers the unique service of connecting parents of children with rare diseases. If you would like to be connected to other parents of children with this disease, please fill out this brief form.

Weblinks

Children's Liver Association for Support Services
C.L.A.S.S. is an all-volunteer, nonprofit organization dedicated to serving the emotional, educational, and financial needs of families coping with childhood liver disease and transplantation.

Children s Liver Disease Foundation
Good website for information about disease treatments and research, support groups, and getting in touch with families of PFIC patients. Note however that this organization is based in the UK.

Canadian Liver Foundation
The Canadian Liver Foundation website provides research, education and patient support programs for all types of liver disease.

Google Search for Byler's Disease

References and Sources

Knisley, A., Agostini, R., Zitelli, B., Kocoshis, S., Boyle, J. Byler's Syndrome. Achieves of Disease in Childhood September 1, 1997; 77(3): 276 - 276. Bull L., Carlton V., Stricker N., et al. Genetic and morphologic findings in progressive familial intrahepatic cholestasis (Byler disease and Byler syndrome): evidence for heterogeneity. Hepatology 1997; 26:155-164 Emedicine.com article: www.emedicine.com/ped/topic2771.htm