Alagille Syndrome

The syndrome is usually diagnosed during infancy or early childhood. Alagille syndrome causes progressive destruction of the bile ducts. Over time, people with Alagille syndrome can develop liver disease.

Alagille syndrome often affects other major organs in the body, including the heart, eyes, kidneys, and spine. Children with Alagille syndrome tend to have unique facial characteristics: a pointy chin, broad brow, and widely spaced eyes.

About one in every 30,000 children is born with Alagille syndrome. It affects boys and girls and people of all races at equal rates.

The symptoms of Alagille syndrome vary from child to child and are more severe in some children than others.

Liver problems are often the first visible sign of this condition. Newborns with Alagille syndrome may have jaundice, a yellowish tint of the eyes and skin, and poor growth during their first few months.

In children more than 3 months old, symptoms may include:

• Persistent jaundice
• Severe itchiness
• Fatty deposits in the skin (xanthomas)
• Dark urine or gray or white stools
• Stunted growth or poor weight gain
• Heart murmur
• "Butterfly" shaped bones in the spinal column
• Specific facial features: pointy chin, broad brow, and widely spaced eyes

Over time, a child with Alagille syndrome may experience one or more of the following complications:

• Malabsorption problems such as diarrhea 
• Poor growth or delayed puberty
• Liver failure
• Portal hypertension
• Heart and blood vessel problems
• Kidney disease

Alagille syndrome is caused by a gene mutation that can pass from parent to child. Between 30 and 50 percent of children with the condition inherit it from one of their parents. In other children, the mutation occurs for no apparent reason.

If one parent has the gene mutation for Alagille syndrome, their children have a 50 percent chance of being born with the mutation. Even though they may not develop symptoms, a child with the gene mutation is considered to have Alagille syndrome and has a 50 percent of chance of passing the mutation on to the next generation.

Although Alagille syndrome is present from birth, it is often not diagnosed until later in childhood, particularly in less severe cases with few symptoms.

To diagnose Alagille syndrome, a clinician will typically conduct a physical examination and order some or all of the following tests:

• Blood test
• Urinalysis
• Eye exam
• X-ray of the spine
• Heart exam
• Liver biopsy
• Genetic testing

Even with extensive testing, Alagille syndrome is difficult to diagnose. If three or more of the following conditions are present, clinicians feel more confident diagnosing Alagille syndrome:

• Symptoms of liver disease such as jaundice, dark urine, or white or gray stool
• Heart murmur
• Butterfly shaped bones in the spine
• Kidney disease
• Partially opaque cornea of the eye, a condition known as posterior embryotoxon
• Facial features associated with Alagille syndrome: pointy chin, broad brow, and widely spaced eyes

Treatment focuses on increasing the flow of bile from the liver to the digestive tract and promoting healthy physical development. Other treatments can alleviate the symptoms of Alagille syndrome and help make children more comfortable.

Medication

A prescription drug called ursodil (ursodeoxycholic acid) can increase the flow of bile from the liver and lower cholesterol levels in the blood.

Antihistamines and other medications often help relieve the itchiness associated with the decreased bile flow.

Nutritional supplements may help the child digest certain types of dietary fat, which can in turn help the child absorb vitamins A, D, E, and K.

Surgery

Currently, there is no surgical procedure that can correct the bile duct system. A liver biopsy may be necessary for an accurate diagnosis.

A child’s long-term outlook depends on how severely they are affected by Alagille syndrome. Ten to 30 percent of people with Alagille syndrome eventually develop advanced liver disease and need a liver transplant.

With proper treatment, however, many people with Alagille syndrome live healthy, normal lives.

The Center for Childhood Liver Disease at Boston Children’s Hospital specializes in helping infants, children, adolescents, and young adults who have a wide variety of liver, gallbladder, and bile duct disorders (otherwise known as hepatobiliary). Doctors refer children with liver disease to this program at Boston Children’s Hospital from all over the world.