Alagille syndrome is a genetic disorder associated with liver, heart, kidney, skeletal, and eye abnormalities as well as a set of characteristic facial features. Facial features associated with Alagille syndrome include a broad, prominent forehead, deep-set eyes, and a small, pointed chin. Also, X-rays often reveal that individuals with Alagille syndrome have butterfly-shaped vertebrae in the spinal column. Generally, Alagille syndrome becomes evident in infancy or early childhood.
In individuals with Alagille syndrome, liver damage is caused by abnormalities in the bile ducts that carry bile, a substance that helps to digest fats, from the liver to the gallbladder and small intestine. Bile ducts in individuals with Alagille syndrome are fewer in number, narrower than normal and malformed. As a result, bile builds up in the liver, causing scarring that prevents the liver from eliminating toxins from the blood.
Alagille syndrome is also associated with heart problems. Blood flow from the heart to the lungs (pulmonicstenosis) may occur in the lower chambers of the heart (ventricular septal defect).
A genetic mutation in the JAG1 gene is responsible for about 90% of all cases of Alagille syndrome. Small deletions of genetic material on chromosome 20, including the JAG1 gene, represent approximately 7% of all reported cases. A very small number of people have mutations on the NOTCH2 gene.
About 30-50% of those with Alagille syndrome inherit the condition from one affected parent. Others are affected by new mutations in the gene or new deletions of genetic material on Chromosome 20 prior to birth. This process occurs randomly during reproductive cell formation in early fetal development and can be present in those with no family history of Alagille syndrome.
Symptoms, though most common in infants, can also occur in children and adults. The most noticeable symptoms reflect those of liver disease and poor bile drainage. These symptoms include:
Some symptoms are unique to Alagille syndrome:
Alagille syndrome is difficult to diagnose, both because the condition is rare and because there are many potential symptoms.
As a rule, three of the following symptoms must be present for an AS diagnosis:
If Alagille syndrome is suspected, genetic bloods test are performed to look for mutations on the JAG1 or NOTCH2 genes.
Treatment for Alagilles syndrome focuses on specific symptoms. These treatments include:
In extreme cases a procedure called partial external biliary diversion (PEBD) may be performed. This procedure entails surgically connecting one end of the small intestine to the gallbladder and the other end to the abdominal opening, called the stoma. This allows bile to leave the body. It is collected in an external bag.
Alagille syndrome is a rare condition affecting about 1 in 70,000 infants.