Alagille syndrome is a rare liver condition that is passed down through families. It occurs due to the liver’s inability to properly remove bile, which is digestive fluid that contains acids, electrolytes, and other substances. This inability is caused by a lack of enough bile ducts to drain bile properly.
Even though Alagille syndrome is primarily considered to be a liver condition, it can also affect other parts of the body, such as the kidneys, heart, eyes, and bones.
This article discusses the symptoms, causes, and treatment options for people with Alagille syndrome.
Alagille Syndrome Signs and Symptoms
Since Alagille syndrome can affect various parts of the body, there are many symptoms associated with the disease. The first signs and symptoms often appear shortly after birth and can include:
- Cholestasis (inadequate bile flow from the liver)
- Jaundice (yellowing of the skin and whites of the eyes)
- Inability to gain weight properly
- Lack of developmental growth following birth
- Severe skin itchiness (cholestatic pruritus)
- Heart murmurs (extra sounds in the heart)
- Congenital heart defects (present since birth)
- A thicker-than-usual ring around the cornea in the eye
- Pale-colored stool or dark urine
- Enlarged liver and spleen
- Blood vessel stenosis (when certain blood vessels are narrower than they should be)
- Bluish skin due to a type of heart disease known as cyanotic heart disease (causes low oxygen levels throughout the blood)
- Possible cognitive or developmental impairment
- Loss of bone mass
- Masses of fat that collect underneath the skin
Because the condition can affect various parts of the body, there are various mild, moderate, and severe complications that can occur if someone inherits it.
Complications of Alagille Syndrome
While not everyone will develop complications, there are common health issues associated with the disease. They include:
- Liver disease and failure
- Issues with the function of both the kidneys and pancreas
- Irregular shaped spinal bones
- Mild vision loss
- Damage to the retina (part of the eye that transfers visual information to the brain for sight)
- Electrical disturbances of the heart
- Malabsorption of nutrients that can lead to another condition known as rickets
- Tetralogy of Fallot (a type of heart condition that presents with four structural abnormalities)
Alagille syndrome is hereditary and occurs when there are mutations to two specific genes: NOTCH2 and JAG1. Both genes are tasked with giving instructions to create a certain protein that is used in what’s called the Notch signaling pathway. This pathway triggers certain actions within the body that are important for fetal development.
The two genes affected in Alagille syndrome are designed to provide the information to this pathway so that it functions properly. When they mutate, that pathway is compromised.4 This causes developmental issues.
This type of hereditary condition is considered to be autosomal dominant, which means that only one copy of the gene has to mutate for the condition to develop. The mutated gene needs to come from just one of the two biological parents. There is a 50% chance that someone will develop Alagille syndrome if one of their biological parents has the mutated gene.3
In many cases, a child can be born with the gene mutation when neither of their parents has the disease.
Physical Features and Alagille Syndrome
When a person is born with Alagille syndrome, both their health and physical features are affected. Roughly 70%–96% of people with the condition will have distinct facial features, such as deep and wide-set eyes, a pointed chin, a broad forehead that shapes the face like an inverted triangle, and a straight nose with a rounded tip.1 These facial features are harder to see in infants, but as a person ages, they become more apparent.