Byler Disease

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This disorder is caused by a problem with the ATP8B1 gene. This gene provides instructions for making protein which takes a role in keeping an appropriate balance of bile acid. This process is needed for the normal releasing of bile and the proper functioning of liver cells. Bile helps the body to digest food.

If you have a problem with the ATP8B1 gene, bile acids build up in liver cells. This results in damaging these cells and the development of liver disease.

We do not know how many people have this disorder. It is very rare with only a small amount of cases that are known. It can affect people from any race or background and affects males and females equally. Increased predisposition for being diagnosed with this disease is in the Inuit population of Greenland and the Old Order Amish population of the United States.

The estimated prevalence for all progressive familial intrahepatic cholestasis (including Progressive familial intrahepatic cholestasis type 1 / Byler Disease) ranges between 1 in 50 000 to 1 in 100 000 births.

The signs and symptoms of Byler Disease are progressive and occur in infancy. Its severity ranges from mild through moderate to severe.

The signs and symptoms of the severe variant include:

• Yellowing of the skin and whites of the eyes (Jaundice)
• Clinically significant diarrhea
• Failure to gain weight and grow at the expected rate (Failure to thrive)
• Hemorrhage (due to the coagulopathy of vitamin K deficiency)
• Enlarged liver and spleen (Hepatosplenomegaly)
• Severe itching of the skin (Pruritus)
• Discolored and/or pale stools
• Cirrhosis and liver disease that may lead to the end stage liver disease if left untreated

The severe variant may lead to an early death.

The signs and symptoms of the mild to moderate variant typically include episodes of jaundice and pruritus. Milder episodes may include pruritus only. Liver disease may be benign in cases.

Other signs and symptoms may include:

• High blood pressure in the vein that supplies blood to the liver (portal hypertension)
• Short stature
• Deafness
• Inflammation of the pancreas (pancreatitis)
• Low levels of fat-soluble vitamins (vitamins A, D, E, and K) in the blood
• Some affected individuals typically develop liver failure before adulthood.

You will be diagnosed after a clinical examination by your specialist or doctor. However, as the signs and symptoms of this disorder are similar to other conditions, you will need further tests. Doctors will analyse your blood, using a special test called a targeted gene panel. In order to rule out other conditions, you may be required to undertake an ultrasound, a liver biopsy, or even surgery.

A multi-disciplinary team of specialists and support networks will be involved in the management of the condition and to offer practical and emotional support.

In severe cases, surgery has been typically involved. When cirrhosis is present, liver transplantation may be required. In milder cases, nasobiliary drainage and extracorporeal liver support are undertaken. The new ileal bile acid transporter inhibitors hold great promise in the treatment of Pruritus. UVB light therapy and plasmapheresis may be also considered. For the treatment of poor growth, medium-chain triglyceride-based formulas may be required. Symptomatic treatment is used for the treatment of fat-soluble deficiencies.

Byler Disease can only be passed on to a child if both parents have a copy of the faulty gene. This is called autosomal recessive inheritance. A person who has a copy of the faulty gene is known as a carrier.

If both parents are carriers, their child has a one in four (25%) chance of inheriting the disorder, and a one in two chance (50%) of being a carrier. This is the same for each child the parents have.

If the child only inherits one copy of the faulty gene, they will be a carrier but will not have the disorder. In some rare cases, carriers have had mild symptoms of the disorder for which they carry the faulty gene.

Once you are diagnosed, you can speak to a genetic counsellor. They can explain how you may have inherited Byler Disease. They can also tell you about genetic testing for the rest of your family. They can provide advice and support if you go on to have children of your own.

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