What is Alagille-Watson Syndrome & How is it Treated?|Causes, Symptoms, Diagnosis of Alagille-Watson Syndrome

What is Alagille-Watson Syndrome?

Alagille-Watson Syndrome affects both male and female equally and is a genetic disorder resulting from the mutation in certain genes. It affects many different parts of the body which in most cases also includes the liver. The number of small bile ducts present inside the liver of a person suffering from Alagille-Watson Syndrome is a lot less than what is found within a healthy person. This is why the liver problems occur. The less number of small bile ducts causes the bile to build up within the liver which sometimes can result in liver damage.

Alagille-Watson Syndrome also affects other parts of the body like the brain, kidneys, heart, eyes, face, blood vessels and even the skeleton. Facial features of the patient might also be affected. The forehead enlarges and becomes prominent, chins become small and pointed and sometimes the eyes also go through certain changes. Alagille-Watson Syndrome is not a common disorder. It is very rare and research shows that between 30,000 and 45,000 individuals, only 1 individual is found to be suffering from Alagille-Watson Syndrome. The frequency of Alagille-Watson Syndrome has not been determined yet as in many cases the disorder remains undiagnosed and in some cases it is also misdiagnosed.

Causes of Alagille-Watson Syndrome

The major cause of Alagille-Watson Syndrome is mutations in the JAG1 and NOTCH2 genes. Though the inherent is autosomal dominant in nature, in many cases the mutation is formed new. In these cases the mutation is not inherited but is created anew.

One of the parents might carry the mutations or sometimes within the affected individual new mutations occur that is the genes change abruptly. If one of the parents carries the mutation then there is a 50% chance of it being passed down to the child during pregnancy irrespective of the gender of the child. Male and female both are affected in equal manner.

The genes in which the mutation occurs are JAG1 and NOTCH2. Research has revealed that the mutation in JAG1 gene, which resides in the short arm (9) of chromosome 20(20p12), is found in 88% of cases, whereas the mutations in NOTCH2 gene, which is located in the short arm of chromosome1, is found in less than 1 percent of cases [1]. In many of these cases the mutations are very random in nature, occurring at any time without any warning sign because of the sudden and spontaneous genetic change or new mutation.

6-7% of cases have revealed that in certain individuals a complete deletion of the JAG1 gene happens. The individuals who go through the complete loss of the JAG1 gene are generally suffering from a very extreme kind of Alagile-Watson Syndrome.

Signs and Symptoms of Alagille-Watson Syndrome

Medical investigators reveal that the signs and symptoms of Alagille-Watson Syndrome are very much present and noticed in the early childhood stage or the infancy stage. There are many signs and symptoms of Alagille-Watson Syndrome. No two persons suffering from Alagille-Watson Syndrome will exhibit similar signs and symptoms. Even if they belong to the same family the symptoms may be quite different. It varies from person to person and so the detection and determination and the proper diagnosis of the disorder might be difficult and sometimes can go misdiagnosed or can also remain undiagnosed, which can cause long term damage within the individual. Thus it is very important to have sufficient knowledge about different signs and symptoms of Alagille-Watson Syndrome.

One of the prominent symptoms of Alagille-Watson Syndrome is the presence of abnormal functions within different parts of the body. The liver, the eyes, the brain, the heart, the skeleton is severely affected. One of the key signs indicating Alagille-Watson Syndrome is the liver disease. In some individuals it may be mild or virtually non-existent whereas in many others it can be severe. In some individuals it may be present in the form of jaundice; some individuals also suffer from mild cholestasis. In many cases where the liver disease is severe it can transform into a progressive liver disease which might potentially lead to liver failure.

The number of individuals who possess a less than normal small bile ducts is quite high. Total 90% of the patients suffering from Alagille-Watson Syndrome have less than normal small bile ducts. Thus the liver disease can confirm the presence of Alagille-Watson Syndrome within the body. The liver’s primary function is the formation of bile. The bile flow helps an individual’s body in many significant ways. It is important in the function of digestion and also when the dietary fats, vitamins and other nutrients need to be absorbed the bile becomes extremely crucial. The bile also helps the body immensely in getting rid of excess cholesterol, bilirubin, waste and toxins. Thus, when the bile flow is disrupted or is facing challenges, the body’s internal functions are very much affected. The vital nutrients are not properly absorbed and toxic materials gather within the body. Again it should be made clear that the above explained symptoms vary, so a person might not have liver disease but still can be suffering from Alagille-Watson Syndrome.

Researchers and medical practitioners have revealed that in approximately 15% of patients, a severe liver disease or progressive liver disease leads to complete liver failure. The nature of progressive liver disease in case of Alagille-Watson Syndrome is such that it is not able to reveal which kids are at risk.

Other signs and symptoms of Alagille-Watson Syndrome is faulty heart or heart defect. In some individuals heart murmur is heard. The heart murmur is the presence of another sound alongside the normal heart beat. Some children also have very complex heart diseases.

Another symptom is defect in the eye. The face also changes a lot. The chins look forward and pointed, the eyes look different than normal, and the forehead enlarges. Skeletal abnormalities happen sometime. Kidneys don’t function properly either. Other parts of the body are also affected.

Prognosis for Alagille-Watson Syndrome

The individuals who exhibit symptoms that are serious in nature must get a treatment. The seriousness of the symptoms depends on many factors like the liver disease and heart disease and how severe and life-threatening they are. It is estimated that almost 15% of individuals suffering from Alagille-Watson Syndrome would ultimately require a liver transplant.

There are people suffering from Alagille-Watson Syndrome who exhibit only one or two minor symptoms. These people do not require treatment.

Diagnosis of Alagille-Watson Syndrome

Before diagnosing the particular symptoms and the patient’s detailed history needs to be taken into account. The symptoms of Alagille-Watson Syndrome are many and varying among individuals, thus the diagnosis becomes a very difficult and tedious process.

The presence of bile duct paucity can be revealed through surgical removal. The bile paucity is an important factor which indicates the presence of Alagille-Watson Syndrome within the body. This characteristic is sometimes not found in infants.

The presence of the symptoms like liver disease, heart defect, eye and skeletal abnormality, and facial features that is different from normal helps immensely in the correct diagnosis.

Molecular genetic test also confirms the presence of Alagille-Watson Syndrome in many cases.

Treatment of Alagille-Watson Syndrome

Alagille-Watson Syndrome is a genetic disorder due to which a complete and absolute cure does not exist. Nevertheless the medical field has come up with certain treatments that can help control the symptoms.

Each individual is treated according to the symptoms that he shows up. A proper treatment requires the combined effort of different specialists.

People with heart disease, liver disease require specific treatment. To improve the bile flow a drug named ursodeoxycholic acid is given to the patient.

Partial biliary diversion, a surgical procedure is performed on infants and children who do not adequately react and respond to medicinal, pharamacologic and dietary therapies.
In cases where the disorder is extremely critical liver transplantation is required.

Standard therapy is used to treat patients with abnormal heart, blood vessel and kidney.

Conclusion

Though the Alagille-Watson Syndrome is a very rare disorder, individuals suffering from Alagille-Watson Syndrome can be treated well. Extra precautions should be taken in the process of diagnosis as a faulty diagnosis can become dangerous and life threatening. The need for proper care is an extreme necessity. Proper treatment will ensure a better and healthy future for the patient. Alagille-Watson Syndrome is a rare disease which affects 1 out of 100,000 people. It cannot be diagnosed easily as there are a wide range of symptoms for Alagille-Watson Syndrome. The children may inherit from their parents or they may face it due to liver problems. Patients may face a hole in the valves of the heart, restricted blood flow from formation of fatty substances, may suffer from kidney problems, jaundice, eye problems, weak bones, etc. Alagille-Watson Syndrome if diagnosed at an early stage can be treated. Liver transplantation can help to increase the life. Various medications and surgeries can be done in order to recover. If people suffer from minor symptoms, they can lead a normal life without any worry.

References:  

  1. Turnpenny, P., & Ellard, S. Alagille syndrome: pathogenesis, diagnosis and management. European Journal Of Human Genetics, (2011). 251-257. doi: 10.1038/ejhg.2011.181

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