Symptoms & Causes for Alagille Syndrome

What are the signs and symptoms of Alagille syndrome?

The most common signs and symptoms of Alagille syndrome are caused by less bile flowing out of the liver. Alagille syndrome may also affect other parts of the body, such as the heart, eyes, face, skeleton, blood vessels, and kidneys.

The signs and symptoms of Alagille syndrome vary, even among people in the same family. Some people with Alagille syndrome may have mild symptoms or may not know they have the disease. Others may have more severe symptoms, health problems, and complications.

Liver signs and symptoms

In Alagille syndrome, the reduced flow of bile out of the liver may lead to the following signs and symptoms

• severe itchiness of the skin, called pruritus
• yellowish color of the whites of the eyes and skin, called jaundice
• darkening of the color of urine and lightening of the color of stools
• fatty deposits that appear as yellow bumps on the skin, called xanthomas
• loose, greasy, bad-smelling stools, a sign that less bile is reaching the small intestine to help digest fats
• an enlarged liver or spleen, which a doctor may notice during a physical exam or imaging tests

These may be the first signs of Alagille syndrome and often appear in the first year of life.⁶ While Alagille syndrome commonly affects the liver, a small number of people with the disease have no signs or symptoms of reduced bile flow or liver disease.

Other signs and health problems

Alagille syndrome can affect many other parts of the body. Doctors may look for the following signs of the disease

• poor growth and energy, caused by the liver problems and other problems
• heart problems such as heart murmur and heart defects that are present at birth
• eye defects such as white or gray-white rings on the corneas, called posterior embryotoxon, which does not affect vision
• facial features such as a wide forehead and a pointed chin and nose
• bones of the skeleton that have an abnormal shape, such as bones in the spine shaped like butterflies, called butterfly vertebrae, which rarely cause problems
• narrowing and weakness in the walls of blood vessels, especially those in the head and neck
• kidney problems, including kidney dysplasia, renal tubular acidosis, and vesicoureteral reflux

What causes Alagille syndrome?

Gene mutations cause Alagille syndrome. Mutations of a gene called JAG1 cause most cases of Alagille syndrome. Mutations of a gene called NOTCH2 cause 1 to 2 percent of cases of Alagille syndrome.⁷

In at least half—50 to 70 percent—of people with Alagille syndrome, the disease is caused by a new gene mutation, meaning that the gene mutation was not inherited from a parent.⁷

In the remainder of people who have Alagille syndrome, the gene mutation for the disease is inherited from a parent. Alagille syndrome is an autosomal dominant disease, meaning that a child can get Alagille syndrome by inheriting a gene mutation from only one parent. Children who have one parent with Alagille syndrome have a 50 percent chance of inheriting the gene mutation and having the disease.⁸

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