Alagille Syndrome: Causes, Symptoms & Treatment

Alagille syndrome is a genetic disorder. The disease is usually referred to by the abbreviation ALGS. Synonymous terms for the disease are arteriohepatic dysplasia or Alagille-Watson syndrome. Alagille syndrome is relatively rare, with a frequency of 1:70000 or 1:100000 thought to occur.

What is Alagille syndrome?

Alagille syndrome has a genetic component. A specific defect on a gene is responsible for the development of the disease. Alagille syndrome received its name in reference to the person who first described the disease. This person was the French scientist Alagille. Alagille syndrome is a hereditary disease that is inherited by children in an autosomal dominant manner. The decisive factor for the development of the disease is the defect of a certain differentiation protein, which is responsible for different types of tissue in the human organism. For this reason, it is possible that many different organ systems of the body become diseased in the course of Alagille syndrome. For example, some individuals show symptoms of the liver. In principle, the individual clinical appearance varies greatly from person to person. It is also characteristic that numerous patients show only minor or no symptoms at all.

Causes

Alagille syndrome has a genetic component. A specific defect on a gene is responsible for the development of the disease. Basically, Alagille syndrome is inherited in an autosomal dominant manner. The penetrance is 100 percent, while the phenotypic appearance varies greatly from patient to patient. In principle, Alagille syndrome is differentiated into two subcategories, which refer to different mutations. Different gene loci are affected. If the mutation is located on the 20th chromosome, the disease is referred to as ALSG1. If the mutation is on the 1st chromosome, it is ALSG2. It is also possible for new mutations to occur. The probability of this is more than 50 percent. Every person who has a corresponding mutation also shows symptoms of the disease in the phenotype. However, the degree of expression of Alagille syndrome differs individually.

Symptoms, complaints, and signs

The complaints that arise in connection with Alagille syndrome are very diverse and often affect several organs. For example, a so-called bile stasis (medical term cholestasis) is typical. In newborn babies, jaundice usually develops. In addition, the facial features of affected patients show striking deviations from the average. The forehead is often very broad. The eyes are deep-set and the chin is usually relatively small. The skeleton also shows anomalies, such as a so-called clinodactyly, shortened distal phalanges, a short ulnar bone, and butterfly vertebrae. Characteristic for the Alagille syndrome are also diseases affecting the eyes and the optic nerves. Possible diseases here are embryotoxon, for example. In addition, affected individuals suffer more often from diseases of the heart. If the liver is diseased in Alagille syndrome, a variety of complaints are possible. These include jaundice, short stature, high pressure of the portal vein, itching, and so-called hypercholesterolemia, in which cholesterol accumulates under the skin. In addition, the spleen enlarges in some patients.

Diagnosis and course

Suspicion of the presence of Alagille syndrome arises in numerous cases from the visual abnormalities of the affected individuals. A visit to an appropriate specialist is advisable to make a definite diagnosis and initiate appropriate treatment. First, the attending specialist discusses the symptoms and medical history with the patient or, in the case of minors, with the patient’s legal guardian. Since Alagille syndrome is a hereditary disease, the family history plays a central role. Following the patient interview, numerous examinations are performed. For example, the spine and heart are x-rayed. The eyes and optic nerves are also examined. In this way, numerous typical anomalies can already be detected that point to Alagille syndrome. To obtain final certainty about the presence of the disease, genetic analysis is used.This makes the corresponding mutations detectable. A biopsy of the liver provides less certainty. It only indicates symptoms and their origin, but not the underlying disease. In the majority of affected individuals, the diagnosis of Alagille syndrome is made on the basis of clinical complaints and typical accompanying symptoms.

Complications

A wide variety of complications may develop in Alagille syndrome, depending on the severity of the disease. If only the liver is affected, for example, itching and redness occur during the course of the syndrome, but often severe kidney disease can also develop, which can later lead to jaundice and hypercholesterolemia. In the long term, Alagille syndrome can lead to short stature, splenomegaly and facial deformities. Characteristics of the condition include widely spaced eyes, a narrow chin, and a large forehead. The syndrome also increases the risk of heart defects, eye malformations, butterfly vertebrae and vascular malformations. Besides, it is mainly the multiform concomitant diseases of Alagille syndrome that lead to severe complications. Thus, mentioned jaundice is associated with deficiency symptoms, fever and a general malaise, while disorders of the immune system are accompanied by increased susceptibility to infections and diseases. If the liver is already severely damaged, this can lead to life-threatening biliary obstruction with severe pain and high fever. Liver transplantation, which is often necessary, can lead to complications such as inflammation and rejection, which in rare cases can be fatal. The earlier action is taken, the less likely severe complications of Alagille syndrome will occur.

When should you see a doctor?

When Alagille syndrome is suspected, a doctor must always be consulted, who can diagnose the hereditary disease and, if necessary, treat it directly. Medical advice is needed at the latest when a newborn shows typical symptoms such as jaundice, complaints of the cardiovascular system, or abnormalities of the face (butterfly vertebrae, bent finger limbs, shortened ulna, and others). Diseases of the eye or the optic nerves also indicate a serious condition that must be clarified. In most cases, the signs of the hereditary disease are already recognized in the hospital and can be treated immediately. If the above-mentioned complaints occur repeatedly in the first months of life and accumulate with increasing age, the pediatrician must be consulted. In addition to Alagille syndrome, there may be other underlying diseases that can have serious consequences if left untreated. It is therefore advisable to seek medical advice at the first suspicion and to have the child examined. The symptoms usually indicate beyond doubt that there is a disease that needs to be treated.

Treatment and therapy

Most people affected by Alagille syndrome do not need any treatment. This is because often the symptoms are only mild. However, depending on the particular organ involvement present, therapy is sometimes necessary. If, for example, the liver is affected by the disease, regular check-ups are necessary, especially in child and adolescent patients. In this way, the course of the disease can be monitored. It may be necessary for affected individuals to take additional vitamins or adhere to certain diets. Liver transplantation is indicated when the organ is increasingly remodeled or patients suffer from itching that can no longer be controlled even with medications. A causal cure of Alagille syndrome is not possible, as it is a genetic disease. Only the symptoms are treated.

Outlook and prognosis

Due to Alagille syndrome, jaundice and biliary congestion occur in most cases already in babies or newborns. Similarly, various malformations and deformities may occur throughout the patient’s body, although the face is usually the most severely affected by the deformities. This can lead to teasing or bullying, especially in children. Likewise, the optic nerves are often affected, so that visual problems may occur under certain circumstances. Likewise, Alagille syndrome negatively affects the heart and can cause various problems and discomforts to the heart.Affected individuals suffer from reduced growth and often from itching. Likewise, there is sometimes an enlargement of the patient’s spleen. The patient’s quality of life is thus significantly reduced by Alagille syndrome. Treatment of Alagille syndrome is not necessary in every case. If the symptoms are only very mild, the syndrome does not need to be treated. However, a causal treatment is not possible, so that only the symptoms can be treated. As a rule, there is no reduced life expectancy.

Prevention

Alagille syndrome represents a hereditary disease, so preventive measures do not exist. Therefore, it is very important to start therapy quickly.

Follow-up

The options for aftercare are usually severely limited in Alagille syndrome. The affected person is always dependent on medical treatment for this condition to relieve the symptoms of the disease. There is no self-healing in the process. Since Alagille syndrome is also a hereditary disease, it cannot be completely cured. If the patient wishes to have children, hereditary counseling is advisable to prevent the syndrome from being passed on to the children. As a rule, those affected are dependent on taking vitamins and various medications. Regular intake should be ensured. Interactions with other medications must also be taken into account in order to prevent complications. Parents must also ensure that children take their medication regularly. Furthermore, regular examinations of the internal organs are necessary in Alagille syndrome in order to detect and treat damage at an early stage. In case of surgical interventions, the affected person should rest and take care of his body after such an intervention. Contact with other sufferers of the disease can also have a positive effect on the course of the disease. In some cases, the patient’s life expectancy is also limited by Alagille syndrome.

Here’s what you can do yourself

Alagille syndrome (ALGS) cannot be treated causally. Nevertheless, if ALGS is suspected, a physician should definitely be consulted to diagnose the disease and treat the symptoms. Under no circumstances should an attempt be made to treat the accompanying symptoms of the disease exclusively by oneself. Whether and what a patient can do himself to improve his symptoms depends on which organs are affected and which accompanying symptoms specifically occur. ALGS is often accompanied by liver disease and jaundice. These disorders must definitely be treated by a doctor. However, naturopathy knows a number of methods that support the therapy of jaundice. For example, garden chervil tea is used. It is prepared by pouring one liter of boiling water over 30 grams of fresh chervil. The tea should be steeped for ten minutes before it is strained, and then it is drunk in cups throughout the day. In the same way tea is prepared from dandelion and daisies or from real soapwort. But in the case of soapwort, the leaves must boil for five minutes. Patients for whom the disease is accompanied by severe itching can be helped by antihistamines from the pharmacy, which are available over the counter as a cream, gel or drops.