Introduction:
Alagille syndrome is a rare disorder that mainly affects the liver. It is found to occur in 1 in every 70,000 newborns. The symptoms usually develop during the first few months after birth. The intensity of the symptoms varies from one person to another.
What Is Alagille Syndrome?
Alagille syndrome is a complex genetic disorder that is inherited within families. It affects the body systems like the liver, heart, eyes, and kidneys. In normal individuals, the liver produces a fluid (bile) carried by bile ducts to other parts (gallbladder, intestine) to help digestion. In patients with Alagille syndrome, the bile ducts are defective and less in number, so the bile gets built up within, causing liver damage.
What Causes Alagille Syndrome?
Changes (deletions) that occur in the genes during the early development of infants are found to cause Alagille syndrome. Most of the patients are affected by alterations in the JAG1 gene and rarely in the NOTCH2 gene.
What Are the Clinical Features of Alagille Syndrome?
-
Liver Damage: As it becomes difficult for the bile ducts to remove bile from the liver, stocking of bile leads to scarring liver tissue and further damage. It also leads to yellowish discoloration of the skin (jaundice) and eyes, dark-colored urine, pale stools, and itchy skin in infancy.
-
Malnutrition: Bile juices produced by the liver are responsible for absorbing and digesting fat and vitamins like A, D, E, and K. Since the bile is not available in adequate amounts in the intestines, poor absorption of vitamins occurs, leading to defective blood clotting, vision problems, rickets, and other growth disturbances (delay in development).
-
Heart Abnormalities: Abnormal sound (murmur) heard with heartbeats and narrowed blood vessels of the lungs (stenosis) are the characteristic features of Alagille syndrome. In a few children, defects in the valves and septum of the heart occur. The most common among them is the tetralogy of Fallot, which causes bluish discoloration of the skin (cyanosis).
-
Eye Defects: Various abnormalities of the eyes are observed during a clinical eye examination. These include the thickening of lines on the eye's surface (cornea), referred to as posterior embryotoxon (PE). The inner layers (retina) of the eye responsible for sending vision images to the brain have degenerated. Vision is not lost, but the clarity of vision is reduced.
-
Facial Deformities like broad forehead, pointed chin, widely spaced, and malformed eyes (hypertelorism) are seen.
-
Bone Defects: Specific spine bones are irregularly shaped, leading to a butterfly-shaped appearance that is usually visualized in the radiographic examination. In a few patients, bone growth is disturbed, and the weakening of bones also occurs.
-
Kidney Abnormalities: The functioning of kidneys, like filtration of blood, are impaired, and rarely the presence of cyst and abnormally small kidneys are also observed.
-
Skin Nodules are whitish and caused by cholesterol deposits in the skin (xanthomas).
-
Other abnormalities like pancreatic insufficiency lead to decreased production of enzymes which eventually causes malnourishment.
-
In specific individuals, Moyamoya syndrome causes narrowing and blockage of the carotid artery that supplies blood to the brain, which later causes serious problems.
How to Diagnose Alagille Syndrome?
The various tools used in diagnosis are:
-
Liver Biopsy: The defective liver tissue is surgically removed and sent for microscopic examination. It will identify tissue scarring and abnormalities of bile ducts in the liver.
-
Blood Tests are done to identify the deficiencies of vitamins and to detect the functioning of the liver by checking the level of a specific protein (albumin) in the blood.
-
Radiographs are taken to visualize any bony defects and view the characteristic butterfly-shaped spinal column.
-
Ultrasound of the abdomen is done to detect pancreas, liver, and spleen abnormalities.
-
An Eye Examination detects classic features like posterior embryotoxon and other vision problems.
-
Electrocardiograms and angiograms detect abnormal heart sounds and blocked blood vessels.
-
Genetic Testing is done to detect the changes in the JAG1 gene that is responsible for causing Alagille syndrome.
What Is the Differential Diagnosis?
The diseases that are similar to Alagille syndrome are as follows:
-
Extrahepatic biliary atresia is an inflammatory disorder of the liver that destroys the bile ducts, leading to bile collection in the liver. The characteristic features include jaundice, liver scarring, itchy skin, pale stools, etc.
-
DiGeorge syndrome is a genetic disorder with clinical features like eye and heart valve defects, butterfly spine, etc. However, liver abnormalities do not occur in this disease.
-
Neonatal hepatitis affects the liver of newborns and has symptoms like pale stools, dark-colored urine, and yellowish discoloration of the skin. But the bile ducts are not damaged in infants with neonatal hepatitis.
How to Treat Alagille Syndrome?
Pharmacological Treatment:
-
Antihistamines like Rifampin and Naltrexone are suggested to get relief from itching.
-
Drugs like Cholestyramine reduce the increased cholesterol levels that cause white nodules on the skin.
-
Ursodeoxycholic acid improves the flow of bile and decreases the production of cholesterol by the liver.
-
Supplements of vitamin A, D, E, and K are given to children to support growth and development. Formulas containing triglyceride, a fat that is easily absorbed, are provided. Extra nutrients, if necessary, are supplied through thin tubes from the nose directly to the abdomen. Or the doctor may also insert a gastrostomy tube through a small opening in the stomach.
Surgical Treatment:
-
When the symptoms are severe and are not managed with medications, the doctor will plan for the following surgeries to improve the quality of life.
-
Liver Transplant: If the liver is severely damaged and its function is wholly worsened, then a decision is made to transplant the liver to increase its functioning.
-
Partial biliary diversion is a surgical procedure done to prevent the circulation of bile within the liver and divert it to the intestines. It is a very effective surgery done in children to reduce the symptoms like itching and fatty deposits in the skin.
-
The doctors may plan for heart surgery to treat any complications due to heart valve or blood vessel defects.
Conclusion:
Patients with Alagille syndrome can lead a good life if the symptoms are corrected and nutritional support is provided early. Well, coordination of the patient to the doctor's advice is essential in treating such diseases.
