What is Alagille Syndrome?
Alagille Syndrome is a genetic condition that affects the liver, heart and other parts of the body. One of the major features of Alagille syndrome is biliary hypoplasia, an incomplete development of the bile duct system resulting in fewer than normal bile ducts inside the liver.
Bile is a fluid made by the liver that helps the body digest fats and absorb fat-soluble vitamins, and also carries toxins and waste products out of the body. Bile ducts drain bile from the liver to the gall bladder for storage and to the small intestine for digestion. In people with Alagille syndrome, the decreased number of bile ducts results in a build up of bile in the liver (cholestasis) and causes damage which can lead to liver scarring, loss of liver tissue and cirrhosis – a chronic condition that prevents the liver from removing toxins from the blood and can lead to liver malfunction and failure.
Alagille syndrome affects approximately one in every 30,000 live births. The number of features and their severity varies between individuals, with some babies being diagnosed when very young yet some people reaching adulthood unaware they have Alagille syndrome.
The Children's Liver Disease Foundation has useful insights from those affected by Alagille syndrome.
Cause
The cause of Alagille syndrome is not fully understood but is known to be partly caused by a genetic mutation. A gene mutation means that the protein made by that gene may not function properly and can lead to a genetic disorder that can then be passed on to the person's children. Almost all gene mutations in Alagille syndrome are in the gene JAGGED1 (JAG1). Approximately 30-50% of people with Alagille syndrome have inherited the gene mutation from a parent, whereas the rest have developed the gene mutation spontaneously.
Symptoms
Signs and symptoms arising from liver damage in Alagille syndrome include prolonged jaundice, a yellow discolouration of the skin and the whites of the eyes lasting longer than 2-3 weeks; dark or yellow coloured urine; or pale, white or grey stools. The Children's Liver Disease Foundation (CLDF) have a stool chart that can be used to compare your babies stools with healthy and potentially unhealthy stools. In addition, itching of the skin known as pruritus is a common sign of liver disease.
These symptoms of liver disease present because the liver is unable to remove bilirubin, a reddish-yellow product formed from the breakdown of the protein haemoglobin found in blood. Normally bilirubin is absorbed and processed in the liver and released in bile. When the bile ducts are blocked bilirubin builds up in the blood causing jaundice and pruritus, enters the urine making it darker in colour, and cannot reach the intestines contributing to the pale stools.
A person with Alagille syndrome may also have xanthomas - fatty deposits that appear as yellow bumps on the skin, most commonly on elbows, joints, tendons, hands, feet, knees or buttocks, are also a common symptom. They are caused by abnormally high cholesterol levels in the blood which is common in people with liver disease.
Several other liver diseases can cause similar symptoms as seen in Alagille syndrome, however there are also specific signs uniquely associated with the disease. People with Alagille syndrome often have distinct facial features including a broad, prominent forehead, deep-set eyes and a small, pointed chin. The disorder may also cause skeletal defects such as butterfly-shaped spinal vertebrae, heart and blood vessel (cardiovascular) defects including heart murmurs, eye abnormalities and kidney disease.
Diagnosis
Diagnosing Alagille syndrome can be difficult due to the variety of signs and symptoms and their severity, and because the syndrome is so rare. Typically, multiple parts of the body need to be affected in order to diagnose Alagille syndrome,and investigations may include a combination of:
There is no cure for Alagille syndrome and treatments aim to improve the quality of life of the patient. This includes medications and therapies to increase bile flow from the liver, promote growth and development of the child and correct nutritional deficiencies. Other symptoms such as cardiovascular defects will continue to be monitored and treated as required.
Increasing bile flow should help with symptoms such as pruritus, however specific medications may be prescribed, and patients may be advised to keep skin moisturised and cut fingernails short to decrease the associated skin damage from scratching.
As malabsorption and poor weight gain and growth can be common complications of Alagille syndrome, dieticians may recommend a high-calorie diet and vitamin supplements for fat-soluble vitamins A, D, E and K. Infants may also be given a special formula to help the small intestine absorb fat.
A liver transplant is only considered for a small subset of patients who have severe liver disease causing cirrhosis or persistent symptoms which cannot be controlled in other ways.
Alagille Syndrome is a genetic condition that affects the liver, heart and other parts of the body. One of the major features of Alagille syndrome is biliary hypoplasia, an incomplete development of the bile duct system resulting in fewer than normal bile ducts inside the liver.
Bile is a fluid made by the liver that helps the body digest fats and absorb fat-soluble vitamins, and also carries toxins and waste products out of the body. Bile ducts drain bile from the liver to the gall bladder for storage and to the small intestine for digestion. In people with Alagille syndrome, the decreased number of bile ducts results in a build up of bile in the liver (cholestasis) and causes damage which can lead to liver scarring, loss of liver tissue and cirrhosis – a chronic condition that prevents the liver from removing toxins from the blood and can lead to liver malfunction and failure.
Alagille syndrome affects approximately one in every 30,000 live births. The number of features and their severity varies between individuals, with some babies being diagnosed when very young yet some people reaching adulthood unaware they have Alagille syndrome.
The Children's Liver Disease Foundation has useful insights from those affected by Alagille syndrome.
Cause
The cause of Alagille syndrome is not fully understood but is known to be partly caused by a genetic mutation. A gene mutation means that the protein made by that gene may not function properly and can lead to a genetic disorder that can then be passed on to the person's children. Almost all gene mutations in Alagille syndrome are in the gene JAGGED1 (JAG1). Approximately 30-50% of people with Alagille syndrome have inherited the gene mutation from a parent, whereas the rest have developed the gene mutation spontaneously.
Symptoms
Signs and symptoms arising from liver damage in Alagille syndrome include prolonged jaundice, a yellow discolouration of the skin and the whites of the eyes lasting longer than 2-3 weeks; dark or yellow coloured urine; or pale, white or grey stools. The Children's Liver Disease Foundation (CLDF) have a stool chart that can be used to compare your babies stools with healthy and potentially unhealthy stools. In addition, itching of the skin known as pruritus is a common sign of liver disease.
These symptoms of liver disease present because the liver is unable to remove bilirubin, a reddish-yellow product formed from the breakdown of the protein haemoglobin found in blood. Normally bilirubin is absorbed and processed in the liver and released in bile. When the bile ducts are blocked bilirubin builds up in the blood causing jaundice and pruritus, enters the urine making it darker in colour, and cannot reach the intestines contributing to the pale stools.
A person with Alagille syndrome may also have xanthomas - fatty deposits that appear as yellow bumps on the skin, most commonly on elbows, joints, tendons, hands, feet, knees or buttocks, are also a common symptom. They are caused by abnormally high cholesterol levels in the blood which is common in people with liver disease.
Several other liver diseases can cause similar symptoms as seen in Alagille syndrome, however there are also specific signs uniquely associated with the disease. People with Alagille syndrome often have distinct facial features including a broad, prominent forehead, deep-set eyes and a small, pointed chin. The disorder may also cause skeletal defects such as butterfly-shaped spinal vertebrae, heart and blood vessel (cardiovascular) defects including heart murmurs, eye abnormalities and kidney disease.
Diagnosis
Diagnosing Alagille syndrome can be difficult due to the variety of signs and symptoms and their severity, and because the syndrome is so rare. Typically, multiple parts of the body need to be affected in order to diagnose Alagille syndrome,and investigations may include a combination of:
- Physical examination
- Heart tests
- X-ray to look for 'butterfly' vertebrae
- Abdominal ultrasound to check for an enlarged liver
- Eye examination
- Blood tests
- Urine tests
- Liver biopsy
- Genetic testing
There is no cure for Alagille syndrome and treatments aim to improve the quality of life of the patient. This includes medications and therapies to increase bile flow from the liver, promote growth and development of the child and correct nutritional deficiencies. Other symptoms such as cardiovascular defects will continue to be monitored and treated as required.
Increasing bile flow should help with symptoms such as pruritus, however specific medications may be prescribed, and patients may be advised to keep skin moisturised and cut fingernails short to decrease the associated skin damage from scratching.
As malabsorption and poor weight gain and growth can be common complications of Alagille syndrome, dieticians may recommend a high-calorie diet and vitamin supplements for fat-soluble vitamins A, D, E and K. Infants may also be given a special formula to help the small intestine absorb fat.
A liver transplant is only considered for a small subset of patients who have severe liver disease causing cirrhosis or persistent symptoms which cannot be controlled in other ways.
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