Alagille Syndrome

Definition

Definition of Alagille Syndrome
Alagille syndrome is a genetic disorder that affects the liver, heart, kidney, and other systems of the body. Problems associated with the disorder generally become evident in infancy or early childhood. The disorder is inherited in an autosomal dominant pattern, and the estimated prevalence of Alagille syndrome is 1 in every 100,000 live births.

Symptoms

Symptoms of Alagille Syndrome
The symptoms of Alagille syndrome and their severity vary, even among people in the same family.

1. Liver Symptoms: Infants with Alagille syndrome may have symptoms of liver disease and poor bile drainage from the liver in the first few weeks of life. These symptoms can also occur in children and adults with Alagille syndrome.
2. Jaundice: Bilirubin is the pigment that gives bile its reddish-yellow color. Jaundice occurs when the bilirubin content in the blood rises, causing yellowing of the skin and whites of the eyes. High levels of bilirubin in the blood can darken the urine, while stools may become pale, gray, or white from a lack of bilirubin in the intestines. Many healthy newborns have mild jaundice due to immaturity of the liver. This type of jaundice disappears by the second or third week of life, whereas the jaundice of Alagille syndrome remains. Infants with jaundice that persists should be checked by a doctor.
3. Pruritus: The buildup of bilirubin in the blood may cause itching, also called pruritus. Pruritus usually starts after 3 months of age and can be severe.

Causes

Causes of Alagille Syndrome
Alagille syndrome is an autosomal dominant disorder, meaning it can be inherited from one parent who has the disorder. A child who has a parent with Alagille syndrome has a 50 percent chance of developing the disorder. Most people with Alagille syndrome have a mutation, or defect, in the Jagged1 (JAG1) gene. Mutations in the NOTCH2 gene are seen in less than 1 percent of people with Alagille syndrome.

Diagnosis

Diagnosis of Alagille Syndrome
Because the symptoms of Alagille syndrome vary and because the syndrome is so rare, the disorder can be difficult to diagnose. The doctor will perform a thorough physical examination to look for clinical symptoms of the disorder. If Alagille syndrome is suspected, the doctor will order one or more of the following tests and examinations:

1. blood tests to check liver function and nutritional status
2. an abdominal ultrasound to look for liver enlargement and to rule out other conditions
3. a liver biopsy to check for a decreased number of hepatic ducts
4. a cardiology examination to check for heart problems
5. an eye examination to check for posterior embryotoxon
6. an x ray of the spine to look for abnormalities
7. examinations of the blood vessels and kidneys to check for abnormalities

Treatment

Treatment of Alagille Syndrome
There is no known cure for Alagille's Syndrome. Most of the treatments available are aimed at improving the functioning of the heart, and reducing the effects of impaired liver function.

1. Medication: Several medications are used to improve bile flow and reduce itching (pruritus): Ursodiol (Actigall), Hydroxyzine (Atarax), Cholestyramine, Rifampicin, and Phenobarbitol have all been used to varying degrees of success. Many patients with Alagille's Syndrome will also benefit from a high dose of a multivitamin such as ADEK (continuing high levels of vitamins A, D, E, and K), as the reduced bile flow makes it difficult to absorb and utilize these vitamins.
2. Surgery: Corrective surgery is sometimes needed to repair heart defects associated with Alagille Syndrome. Also, because the pulmonary arteries are often narrow in patients with Alagille syndrome, a catheterization process similar to angioplasty may be used to widen the arteries to reduce pressure on the heart's pumping valves. In moderate to severe cases, stents may be placed in the arteries to increase their diameter. Transplantation of the liver has been a successful alternative to medication in severe cases.

Prognosis

Prognosis of Alagille Syndrome
The outlook for people with Alagille syndrome depends on several factors, including the severity of liver damage and heart problems and the early correction of malabsorption. Predicting who will experience improved bile flow and who will progress to end-stage liver failure is difficult. Fifteen percent of people with Alagille syndrome will eventually require a liver transplant.

Survival rates for people receiving liver transplants have improved over the past several years because of newer drugs that suppress the immune system and keep it from attacking and damaging the new liver.

Prevention

Prevention of Alagille Syndrome
Alagille syndrome can affect other parts of the body in ways that may help doctors distinguish it from other liver conditions.