Alagille syndrome

What is Alagille syndrome?

It is a Genetic disorder(JAG 1 gene)  also known as arteriohepatic dysplasia.Children  usually have a liver disease characterized by a progressive loss of the bile ducts within the liver over the first year of life and narrowing of the bile ducts outside the liver. This leads to a buildup of bile in the liver, causing damage to liver cells. Scarring may occur and lead to cirrhosis in about 30 to 50 percent of affected children.

How common is this condition?

The incidence rate is approximately 1 case in every 100,000 live births.

What is the cause and risk of developing syndrome?

 The disease is inherited from one parent and there is a 50 percent chance that each child will develop the syndrome. Each affected adult or child may have all or only a few of the features of the syndrome. Frequently, a parent or brother or sister of the affected child will share the facial appearance, heart murmur or butterfly vertebrae, but have a completely normal liver and bile ducts

What are the presentation of disease?

Symptoms of the illness are jaundice (yellowing of skin and eyes), pale, loose stools and poor growth within the first three months of life. Later there is persistent jaundice, itching, fatty deposits in the skin, and stunted growth and development during early childhood. Frequently, the disease stabilizes between ages 4 and 10 with an improvement in symptoms.

What are the other systems which get affected by the disease?

Other features that help establish the diagnosis include abnormalities in the cardiovascular system, the spinal column, the eye, and the kidneys. Narrowing of the blood vessels connecting the heart to the lungs (pulmonary artery) leads to extra heart sounds but rarely problems in heart function.
 Facial features include a prominent, broad forehead, deep-set, widely spaced eyes, broad forehead, malformed or low-set ears, a long, straight nose and a small pointed chin. More than 90 percent of children with Alagille syndrome have an unusual abnormality of the eyes. An extra, circular line on the surface of the eye requires specialized eye examination to detect and does not lead to any disturbances in vision. Patients may also develop kidney problems (nephropathy).

Does child  with Alagille syndrome have vitamin deficiency?

Problems with fat digestion and absorption may lead to deficiency of fat-soluble vitamins - A, D, E and K.Vitamin A deficiency causes night blindness and red eyes. Vitamin D deficiency causes softening and fractures of the bones and teeth (rickets). Vitamin E deficiency causes a disabling disease of the nervous system and muscles, and vitamin K deficiency causes bleeding problems.

How to diagnose Alagille syndrome?

Diagnosis is often based on the medical history, physical examination, and blood tests. Radiologic tests and liver biopsy (sampling tissue for analysis) may be necessary.

What is the treatment for this condition?

Treatment is primarily medical and not surgical.Basic aim of the treatment is to prevent bile stagnation in liver and to correct nutritional deficiency. Itching caused by the buildup of bile in the blood and skin may be relieved by medications including diphenhydramine (Benadryl) and hydroxyzine hydrochloride (Atarax).  Although reduced flow of bile into the intestine leads to poor digestion of dietary fat, a specific type of fat can still be well digested and therefore infant formulas containing high levels of medium-chain triglycerides - MCT - are usually substituted. Deficiencies of the vitamins A, D, E, and K can usually be corrected by oral doses.

What is the role of surgery?

Sometimes, surgery is necessary during infancy to help establish the diagnosis of Alagille syndrome(Rule out biliary atresia) by direct examination of the bile duct system. However, surgical reconstruction of the bile duct system is often not recommended. Occasionally, liver cirrhosis advances to a stage where the liver fails to perform its functions. Liver transplantation is then considered.

What is the prognosis of the children suffering from Alagille syndrome?

Estimated 20-year survival rates are 80% for those not requiring liver transplantation and 60% for those requiring transplantation. Among children with cholestatic liver disease, 1-year and 5-year survival after liver transplantation is significantly lower in children with Alagille syndrome than in children with biliary atresia. The 20-year predicted survival  for those with significant intracardiac lesions is 40% while the 20-year predicted survival for those without intracardiac lesions is 80%.

Important Articles on Alagille syndrome

1. Alagille syndrome: spectrum of clinical presentation in India.

    http://www.ncbi.nlm.nih.gov/pubmed/22692667

    Gupta P, Bhakhri BK, Paul P.

    Indian J Gastroenterol.2012Jun;31(3):149-50.doi:10.1007/s12664-012-0199-8. No abstract available.

    PMID: 22692667 [PubMed - indexed for MEDLINE]

2. Alagille syndrome: a rare disease in an adolescent.

   http://www.ncbi.nlm.nih.gov/pubmed/22678460

    Guru Murthy GS, Rana BS, Das A, Thapa BR, Duseja AK, Dhiman RK, Chawla YK.

    Dig Dis Sci. 2012Nov;57(11):3035-7. doi:10.1007/s10620-012-2226-0.Epub 2012Jun 8. No abstract

    available.

    PMID: 22678460 [PubMed - indexed for MEDLINE]

3. Alagille syndrome with prominent skin manifestations.

    http://www.ncbi.nlm.nih.gov/pubmed/16394388

    Sengupta S, Das JK, Gangopadhyay A.

    Indian J Dermatol Venereol Leprol. 2005 Mar-Apr;71(2):119-21.

    PMID: 16394388 [PubMed - indexed for MEDLINE] Free Article

4. Alagille syndrome.

   http://www.ncbi.nlm.nih.gov/pubmed/12420920

    Shendge H, Tullu MS, Shenoy A, Chaturvedi R, Kamat JR, Khare M, Joshi A.

    Indian J Pediatr. 2002 Sep;69(9):825-7. Review.

    PMID: 12420920 [PubMed - indexed for MEDLINE]

5. Alagille syndrome.

   http://www.ncbi.nlm.nih.gov/pubmed/12420916

    Hadchouel M.

    Indian J Pediatr. 2002 Sep;69(9):815-8. Review.

    PMID: 12420916 [PubMed - indexed for MEDLINE]

6. Alagille syndrome. A case report.

   http://www.ncbi.nlm.nih.gov/pubmed/1981431

    Nigale V, Trasi SS, Khopkar US, Wadhwa SL, Nadkarni NJ.

    Acta Derm Venereol. 1990;70(6):521-3.

    PMID: 1981431 [PubMed - indexed for MEDLINE].

 

 

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