Alagille Syndrome

What is Alagille syndrome?

Alagille syndrome is an inherited disorder that closely resembles other forms of liver disease seen in infants and young children. However, a group of unusual features affecting other organs distinguishes Alagille syndrome from the other liver and biliary diseases of infants.

Children with Alagille syndrome usually suffer a progressive loss of the bile ducts within the liver over the first year of life and narrowing of bile ducts outside the liver. This leads to a buildup of bile in the liver, causing damage to liver cells. Scarring may occur and lead to cirrhosis in about 30 to 50% of affected children.

What are the symptoms of Alagille syndrome?

Symptoms of Alagille syndrome are jaundice; pale, loose stools; and poor growth within the first three months of life. Later, there is persistent jaundice, itching, fatty deposits in the skin, and stunted growth and development during early childhood. The disease often stabilizes between ages four and ten with an improvement in symptoms.

Other features, which help establish the diagnosis, include abnormalities in the kidneys, cardiovascular system, eyes, and spine. Narrowing of the blood vessel connecting the heart to the lungs leads to heart murmurs but rarely causes problems in heart function. The shape of the bones of the spinal column may look like the wings of a butterfly on x-ray, but this shape almost never causes any problems with function of the nerves in the spinal cord.

More than 90% of children with Alagille syndrome have an unusual abnormality of the eyes. An extra, circular line on the surface of the eye can be detected during a specialized eye examination. In addition, some children may have some changes in kidney function.

Many physicians believe that there is a specific facial appearance shared by most of the children with Alagille syndrome that makes them easily recognizable. The features include a prominent, broad forehead; deep-set eyes; a straight nose; and a small pointed chin.

What causes Alagille syndrome?

Alagille syndrome is a genetic condition (associated with the Notch signaling pathway and Jagged1 gene) that causes narrowed and malformed bile ducts in the liver. Bile that cannot flow through the deformed ducts builds up in the liver and causes scarring. The scar tissue prevents the liver from working properly to eliminate wastes from the bloodstream.

How is Alagille syndrome diagnosed?

A diagnosis of Alagille syndrome usually depends upon finding several different components of the syndrome in an individual. Generally, the syndrome involves five distinct findings, including reduced bile flow, congenital heart disease, bone defects, a thickening of a line on the surface of the eye, and particular facial features. Diagnosis can be confirmed by genetic analysis.

How is Alagille syndrome treated?

Treatment of Alagille syndrome focuses on trying to increase the flow of bile from the liver, maintaining the child’s normal growth and development pattern, and correcting any of the nutritional deficiencies that often develop. Because bile flow from the liver to the intestine is slowed in Alagille syndrome patients, medications designed to increase the flow of bile are frequently prescribed.

While reduced bile flow into the intestine leads to poor digestion of dietary fat, a specific type of fat can still be well digested, and therefore infant formulas containing high levels of medium-chain triglycerides (MCT) are usually substituted for conventional formulas. Some infants can grow adequately on breast milk if additional MCT oil is given. There are no other dietary restrictions.

Problems with fat digestion and absorption may lead to deficiency of fat-soluble vitamins (A, D, E, and K). Deficiencies of these vitamins can be diagnosed by blood tests and can usually be corrected by large oral doses. If the child's system cannot absorb vitamins given by mouth, vitamin injections into the muscle may be necessary.

Sometimes surgery is necessary during infancy to help establish the diagnosis of Alagille syndrome by direct examination of the bile duct system and through liver biopsy. However, surgical reconstruction of the bile duct system is not recommended because bile can still flow from the liver, and there is presently no procedure that can correct for the loss of the bile ducts within the liver. Occasionally, liver cirrhosis advances to a stage where the liver fails to perform its functions. Liver transplantation is then considered.

If my child has been diagnosed with Alagille syndrome, what should I ask our doctor?

Speak to your doctor about your child’s dietary needs and the possible paths that the disease may take.

Who is at risk for Alagille syndrome?

Alagille syndrome is generally inherited only from one parent and there is a 50% chance that each child will develop the syndrome. The genetic basis has recently been defined and the “Alagille gene” has been found. Each affected adult or child may have all or only a few of the features of the syndrome. Frequently, a parent, brother, or sister of the affected child will share the facial appearance, heart murmur, or butterfly vertebrae, but have a completely normal liver and bile ducts.

Via: American Liver Foundation