What Is Byler Disease?

Each day, your liver makes a fluid called bile. Bile helps you digest food by breaking down the fats you eat. It also helps you absorb certain vitamins (fat-soluble vitamins) and removes waste products your body doesn’t need.

“Bile is the natural detergent our bodies make,” says James Squires, MD, MS, a pediatric gastroenterologist at UPMC Children’s Hospital of Pittsburgh. “When we eat fats and things that are filled with fat molecules, bile allows us to break those things down to be absorbed by our intestine.”

Typically, bile leaves your liver through a series of tubes called ducts. Some bile enters your small intestine to help with digestion, and some goes to your gallbladder for storage. But sometimes, changes to certain genes cause disorders that affect how bile leaves the liver.

Byler disease is a rare disorder that affects bile flow and can cause liver failure in some children. Here, Dr. Squires helps explain Byler disease and how it may affect your child’s liver.

What Is Byler Disease?

Byler disease is a type of progressive familial intrahepatic cholestasis (PFIC). Cholestasis is a condition that prevents bile from leaving the liver as it should. In Byler disease, cholestasis happens inside the liver (intrahepatic) rather than in the ducts outside the liver.

PFIC is a group of disorders that are progressive, which means they get worse over time. Familial means the disorder usually affects members of the same family. There are three classic types of progressive familial intrahepatic cholestasis — PFIC1, PFIC2, and PFIC3, with newer types being described as we increase the understanding of the complexity of bile flow.

Never Miss a Beat!

Get Healthy Tips Sent to Your Phone!

Message and data rates may apply. Text the word STOP to opt out and HELP for help. Click here to view the privacy and terms.

What Causes Byler Disease?

A different genetic change causes each type of PFIC. Byler disease — PFIC1 — occurs when there’s a change to the ATP8B1 gene.

Genes tell your body how to make proteins that do certain jobs. According to Dr. Squires, there are many different proteins involved in moving bile out of your liver. When there’s a change to the ATP8B1 gene, bile acids build up and liver cells become damaged.

“Genes are like an instruction manual that tells our body how to make every protein,” Dr. Squires says. “In people who have these genetic disorders, the instruction manual has a mistake in it.”

Who Gets Byler Disease?

Byler disease occurs in about 1 in 50,000 to 100,000 babies. “It’s very rare,” Dr. Squires says.

Babies with Byler disease inherit gene changes from their parents in an autosomal recessive pattern. This means each parent has one copy of the changed gene and passes it to their child.

Anybody can develop Byler disease. But the condition is much more common in certain communities, such as among people of Amish descent.

Byler Disease Symptoms

Babies with Byler disease can’t get bile acids out of the liver and into the intestine where they belong, Dr. Squires says. Bile salts — a component of bile — build up in the liver and cause symptoms like:

  • Yellow skin or eyes (jaundice).
  • Itchy skin.
  • Malnutrition.
  • Diarrhea.
  • Inflamed pancreas (pancreatitis).

Children with Byler disease are more likely to have short stature. They may also be more likely to have deafness.

How Do Doctors Diagnose Byler Disease?

Jaundice is the most common symptom doctors see in babies with Byler disease, Dr. Squires notes. “It’s a clear sign of something inherently wrong with the liver,” he says.

Doctors diagnose Byler disease — and other types of PFIC — with a simple blood test called a targeted gene panel. They take a blood sample and send it to specialists who look for specific changes in the genes.

Most babies are about 3 months old when they’re diagnosed with Byler disease. But very young babies who have jaundice may need tests to make sure they don’t have biliary atresia. Biliary atresia causes blocked bile ducts inside and outside the liver and can lead to liver scarring and failure.

“Byler disease can look similar to biliary atresia,” Dr. Squires says. “Sometimes, we may do an ultrasound, a liver biopsy, or even surgery to rule out biliary atresia.”

Byler Disease Treatment

When bile reaches a part of the small intestine (the terminal ileum), it interacts with a protein called the ileal bile acid transporter (IBAT). “It allows bile acids that aren’t used as detergents to be reabsorbed and recycled,” Dr. Squires says. But reabsorption of bile acids adds to the buildup of toxic bile salts in children with Byler disease.

Stopping bile acid absorption in the terminal ileum can help relieve itching, according to Dr. Squires.

Treating Byler disease has historically involved surgery, he says. Children undergo a surgery called biliary diversion. Surgeons make changes to the way bile flows from the liver into the intestine.

The most common surgery to treat Byler disease is partial external biliary diversion. Surgeons reroute bile through the wall of the abdomen. Bile collects in a pouch outside the body (ostomy bag).

Though surgery has been the standard treatment for Byler disease, Dr. Squires says new medications may offer options. He notes that drugs called IBAT inhibitors show promise in treating the disorder.

“These medications block the reabsorbing of bile acid in the terminal ileum,” he says. “It’s a way to give a medicine and hopefully accomplish the same thing as a surgical diversion.”

Some children with PFIC experience scarring (cirrhosis) and liver failure. A liver transplant, whether from a deceased donor or a living donor, can offer life-saving treatment.

The Future of Byler Disease Treatment

Researchers continue to study new medications to treat Byler disease. And Dr. Squires says he’s hopeful that they’ll offer new options for children with this condition. Still, he notes, Byler disease is a serious disorder that will likely need lifelong medical care.

Though researchers continue to study PFIC and its causes, there’s a lot doctors don’t know, he says. “We’re learning all the time about how to better handle these conditions.”

If your child has Byler disease, Dr. Squires wants you to know you’re not alone. He tries to help parents of children with this condition connect with the PFIC support community. “We try to give parents a sense of community and let them know there are folks out there who can help them,” he says.

Sources

MedlinePlus, Cholestasis Link

Merck Manual Consumer Version, Gallbladder and Biliary Tract Link

MedlinePlus, Progressive familial intrahepatic cholestasis Link

National Institute of Diabetes and Digestive and Kidney Diseases, Biliary Atresia Link

PFIC Voices®, Progressive Familial Intrahepatic Cholestasis Link

UPMC Children's Hospital of Pittsburgh, Byler Disease Link

About Pediatrics

From nutrition to illnesses, from athletics to school, children will face many challenges growing up. Parents often will make important health care decisions for them. We hope to help guide both of you in that journey. UPMC Children’s Hospital of Pittsburgh is a national leader in pediatric care, ranking consistently on U.S. News & World Report’s Best Children’s Hospitals Honor Roll. We provide expert treatment for pediatric diseases, along well-child visits, urgent care, and more. With locations across Pennsylvania, Maryland, and West Virginia, you can find world-class care close to home. We also work closely with UPMC Magee-Womens Hospital, a national leader in care for newborns and their mothers. Our goal is to provide the best care for your children, from birth to adulthood and beyond. Visit our website to find a doctor near you.