Alagille syndrome (NORD)
Definitions & Key takeaways
Alagille syndrome (NORD) is a rare, autosomal dominant disorder that affects the liver, heart, and other parts of the body. The most common symptom of Alagille syndrome is jaundice (yellowing of the skin and eyes) in infancy. Other symptoms may include malformed bones, kidney problems, and irregular developmental milestones. There is no cure for Alagille syndrome, but many affected individuals can lead normal, productive lives with proper care.
Alagille syndrome, or ALGS, is a genetic disorder that can affect multiple organs in the body and cause a variety of abnormalities.
Alagille syndrome typically affects the liver but it can also cause problems in the heart, kidney, eyes, and bones. One of the main liver features of Alagille syndrome is the disruption of bile flow from the liver to the gallbladder.
Affected individuals have a reduced number of bile ducts in the liver. As a result, there is a decrease in bile flow, also known as cholestasis.
The symptoms and signs of cholestasis include jaundice, or the yellowing of skin and eyes, severe itching, pale colored stools, and dark urine.
Some patients may also have an enlarged spleen or liver. Because many necessary vitamins and nutrients need bile to be properly absorbed, people with Alagille syndrome may also experience select vitamin deficiencies, or poor weight gain and growth.
Deficiencies in specific vitamins may result in vision problems from a lack of Vitamin A, bone weakness from a lack of vitamin D, developmental delays from a lack of Vitamin E, and blood clotting problems from a lack of Vitamin K.
The heart can also be impacted by Alagille syndrome. The most common finding in ALGS patients is peripheral pulmonary arterial stenosis.
This means that the blood vessels carrying blood to the lungs are narrowed. The stenosis typically manifests as a heart murmur, or an extra sound in the heartbeat.
Symptoms are based on the degree of narrowing of the blood vessel and some people may have no symptoms while others may have dizziness, shortness of breath, increased sweating, chest pains, and cyanosis, or bluish colored skin.
Children with Alagille syndrome may also have congenital heart defects, or heart problems that one is born with. The most common congenital heart defect in ALGS patients is tetralogy of Fallot.
Other possible defects include atrial septal defects, patent ductus arteriosus, and coarctation of the aorta. Congenital heart defects may result in dizziness and fainting, fatigue, shortness of breath, swelling in the hands, cyanosis and developmental delay.
There are many distinct facial features that are characteristic of Alagille syndrome. These include a broad forehead, deeply set and widely spaced eyes, and a pointed chin.
In the eyes, Alagille syndrome can cause a thickened lining of the cornea called posterior embryotoxon. This finding should not affect vision.
Some patients may have irregularly shaped bones in the vertebrae called butterfly vertebrae. Other symptoms include abnormalities in the kidney or pancreas, stenosis of other blood vessels throughout the body, and mild cognitive impairment.
Most people with Alagille syndrome have a mutation in the JAG1 gene. However, some patients have a mutation in the NOTCH2 gene instead.
These mutations are inherited in an autosomal dominant manner which means only a single copy of the mutated gene is necessary to cause the disorder.
If a parent carries the mutated gene, there is a 50% chance that they will pass the gene on to each of their offspring. However, about half of Alagille syndrome cases are caused by a de novo mutation, meaning they arise on their own and are not inherited.
Diagnosis of Alagille syndrome is primarily based on an individual’s symptoms and signs. Traditionally, diagnosis is made if there are at least 3 out of 5 of the following: distinct facial features, eye abnormalities, heart defects, symptoms of liver disease and skeletal abnormalities.
If ALGS is suspected in a patient, a liver biopsy is done to look for a decreased number of bile ducts. The diagnosis can be confirmed if genetic testing identifies a mutation in the JAG1 or NOTCH2 gene, but some patients do not have a mutation in one of these genes.
Treatment for Alagille syndrome varies depending on the specific symptoms. It will often require a coordinated effort within the individual’s care team including pediatricians, gastroenterologists, cardiologists, and others to monitor symptoms over time.
Supplemental treatment with vitamins and nutrients can help with growth problems. In some patients the drug ursodeoxycholic acid can be prescribed to improve bile flow.
Severe itching can be improved through adequate hydration of the skin as well as some treatments including antihistamines, rifampin, cholestyramine, and naltrexone.
Some affected infants and children who do not respond to dietary and drug treatments may require a surgery known as partial biliary diversion to increase bile flow.
In cases of severe progressive liver disease, liver transplant may be required. For those with confirmed diagnoses, genetic counseling is suggested to evaluate and understand family risks.
##Summary Alright, as a quick recap... Alagille syndrome is a genetic disorder that is mainly characterized by liver disease, heart defects, and distinct facial features.
Affected individuals may also have eye findings and skeletal abnormalities. Alagille syndrome is diagnosed through clinical signs and symptoms or molecular genetic testing.
Treatment for Alagille syndrome requires a coordinated approach that targets the various symptoms of a particular individual.
These treatments include supplemental feeding, drug therapies, and sometimes surgery. various symptoms of a particular individual these treatments include supplemental feeding
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