Alagille Syndrome

What Is Alagille Syndrome?

Alagille syndrome is a rare genetic disorder that affects the liver and sometimes other parts of the body such as the heart, eyes, bones, kidneys, blood vessels and nervous system.  

People with Alagille syndrome have fewer bile ducts than normal in the liver, or bile ducts that are narrow or misshapen. Bile ducts are small tubes that move bile out of the liver. Bile helps the body absorb and utilize the fat in the foods we eat. When the bile ducts are unable to move the bile through, it collects in the liver and affects the organ's ability to function. 

Alagille syndrome varies greatly from person to person. The condition may affect different organs in different people; it may also affect some organs more seriously. Many people with Alagille syndrome have only mild symptoms and can lead normal lives with normal life expectancy. A small percentage of people with the syndrome, however, may have severe and life-threatening complications. 

Who Is Most at Risk for Alagille Syndrome?  

Alagille syndrome is considered a rare condition, affecting approximately 1 in every 30,000 to 50,000 births. It can occur in people of any racial or ethnic background and affects males and females equally. 

The condition is often caused by a gene mutation that passes from parent to child. Children who have one parent with Alagille syndrome have a 50 percent chance of inheriting the gene mutation and having the disease. 

Between 30 and 50 percent of children with Alagille syndrome inherit it from one of their parents. In other people, the condition is caused by a new (spontaneous or sporadic) gene mutation not inherited from a parent.

What Causes Alagille Syndrome?  

Alagille syndrome is caused by mutations in the JAG1 or NOTCH2 genes, which play a crucial role in organ development during embryonic growth. Whether a child inherits the gene mutation from a parent or spontaneously, nothing parents do can cause or prevent the mutation from occurring. 

What Are Signs and Symptoms of Alagille Syndrome?  

Alagille syndrome is present at birth, but signs and symptoms may not become apparent until later in life. Symptoms vary from child to child and can range from mild to severe.  

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

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

• Persistent jaundice 
• Severe itchiness of the skin (pruritus) 
• Dark urine or gray or white stools 
• Poor growth or poor weight gain due to insufficient bile to digest and absorb fat 
• Deficiency of vitamins A, D, E and K, which depend on bile acids for digestion and absorption 
• Heart murmur 
• “Butterfly” shaped bones in the spinal column 
• Distinct facial features: pointed chin, large forehead and widely spaced and deep-set eyes 
• Hard white or yellow nodules in the skin (xanthomas) that develop due to fatty deposits 

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

• Enlarged liver or spleen 
• Malabsorption problems such as diarrhea 
• Eye abnormalities such as white or gray-white rings on the corneas (posterior embryotoxon), which does not affect vision 
• Weak bones 
• Poor growth or delayed puberty 
• Liver failure 
• Portal hypertension 
• Heart and blood vessel abnormalities 
• Problems with kidney function or structure 
• Developmental delays  

How Is Alagille Syndrome Diagnosed?  

Alagille syndrome is usually diagnosed during infancy or early childhood. The variation in symptoms and severity can make it difficult to diagnose. The diagnostic process will likely include:  

• Clinical evaluation, including a physical examination to look for characteristic signs and symptoms of Alagille syndrome 
• Blood tests to assess liver function, including levels of liver enzymes and bilirubin 
• Imaging tests such as ultrasound, magnetic resonance imaging (MRI) and/or CT scans to visualize the liver and other affected organs. These tests can help identify abnormalities such as bile duct paucity (reduced number of bile ducts) and liver enlargement 
• Other tests such as urinalysis, eye exam, spinal X-ray, heart exam, kidney or pancreas function tests and/or liver biopsy 
• Genetic testing to identify abnormal genes associated with Alagille syndrome 

Depending on the specific symptoms and complications present, your child may be referred to specialists at Lurie Children’s including pediatric hepatologists, cardiologists, geneticists, nephrologists and ophthalmologists for further evaluation and management. 

How Is Alagille Syndrome Treated? 

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

• Medications such as antihistamines to alleviate symptoms like itching (pruritus), or bile acid-binding resins to improve bile flow. 
• Nutritional Support: Children with Alagille Syndrome may require specialized diets or nutritional supplements to ensure adequate digestion, growth and development. In severe cases of liver dysfunction, nutritional support may be provided through tube feeding or intravenous nutrition. 
• Monitoring and Surveillance: Regular monitoring of liver function, growth parameters and developmental milestones is essential for detecting and managing complications early. Patients may require periodic blood tests, imaging studies and consultations with specialists to monitor their condition closely. 
• Surgical interventions may be required to address specific complications such as congenital heart defects. Bile duct surgery or liver transplantation may be considered for severe liver dysfunction. 

Alagille syndrome affects each person diagnosed with the condition differently, even within the same family. Some people will experience very mild symptoms while others might need more treatment or surgery to combat severe symptoms. 

Early diagnosis and treatment can minimize the effects of the condition and prevent life-threatening symptoms. 

What Is the Long-term Outlook for Alagille Syndrome? 

There is no cure for Alagille syndrome. It is a lifelong condition, and the long-term outlook for people who have it can vary widely depending on the severity of symptoms and presence of complications.  

The severity of liver disease in children with Alagille syndrome typically peaks by 3 to 5 years of age and often resolves by 7 to 8 years of age. With appropriate medical management, many patients can maintain stable liver function and lead relatively normal lives. In other cases, liver disease will progress. Approximately 15 percent of patients with Alagille syndrome will require liver transplantation. 

The long-term prognosis for cardiac complications associated with Alagille syndrome depends on the specific type and severity of the heart defect. Some heart abnormalities may require surgical correction, while others may be managed with medications and close monitoring. 

Children with Alagille syndrome may experience growth delays and developmental challenges. Lurie Children’s takes a comprehensive approach and offers individualized support for each patient.  

Your child may be referred to the Division of Gastroenterology, Hepatology and Nutrition, one of the leading programs in the country for evaluating and treating conditions that affect digestion and nutrition. 

With appropriate treatment and support, many individuals with Alagille syndrome can lead healthy, normal lives. While the condition presents unique challenges, ongoing follow-up with a multidisciplinary care team can significantly improve outcomes and quality of life for your child.