Alagille syndrome
| Alagille syndrome | |
|---|---|
| Classification and external resources | |
| ICD-10 | Q44.7 (EUROCAT Q44.71) |
| ICD-9 | 759.89 |
| OMIM | 118450 |
| DiseasesDB | 29085 |
| eMedicine | ped/60 |
| MeSH | D016738 |
Alagille syndrome is a genetic disorder that affects the liver, heart, kidney, and other systems of the body. Problems associated with the disorder generally become evident in infancy or early childhood. The disorder is inherited in an autosomal dominant pattern, and the estimated prevalence of Alagille syndrome is 1 in every 100,000 live births.
It is named for Daniel Alagille.[1][2]
Contents |
[edit] Presentation
The severity of the disorder can vary within the same family, with symptoms ranging from so mild as to go unnoticed to severe heart and/or liver disease requiring transplantation.
Signs and symptoms arising from liver damage in Alagille syndrome may include a yellowish tinge in the skin and the whites of the eyes (jaundice), itching, and deposits of cholesterol in the skin (xanthomas). A liver biopsy may indicate too few bile ducts (bile duct paucity). Other signs of Alagille syndrome include congenital heart problems, particularly Tetralogy of Fallot, an unusual butterfly shape of the bones of the spinal column that can be seen in an x-ray, certain eye defects and narrow arteries that can lead to brain bleeds/ haemorrhages. Many people with Alagille syndrome have similar facial features, including a broad, prominent forehead, deep-set eyes, and a small pointed chin. The kidneys and central nervous system may also be affected.
[edit] Pathophysiology
Microdeletion of the 20p12 gene corresponding to JAG1 results in Alagille syndrome, similar to the inheritance pattern of Williams syndrome.[3] The JAG1 gene is involved in signaling between adjacent cells during embryonic development. This signaling influences how the cells are used to build body structures in the developing embryo. Mutations in JAG1 disrupt the signaling pathway, causing errors in development, especially of the heart, bile ducts in the liver, spinal column, eyes, blood vessels and certain facial features.
NOTCH2 is also associated with Alagille syndrome.[4]
Narrowed and malformed bile ducts in the liver produce many of the health problems associated with Alagille syndrome. Bile is produced in the liver and moves through the bile ducts into the small intestine, where it helps to digest fat. In Alagille syndrome, the bile builds up in the liver and causes scarring that prevents the liver from working properly to eliminate wastes from the bloodstream.
[edit] Genetics
This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene is sufficient to cause the disorder. In some cases, an affected person inherits the mutation from one affected parent. Other cases may result from new mutations in the gene. These cases occur in people with no history of the disorder in their family.
[edit] Treatment
There is no known cure for Alagille's Syndrome. Most of the treatments available are aimed at improving the functioning of the heart, and reducing the effects of impaired liver function.
[edit] Medication
Several medications are used to improve bile flow and reduce itching (pruritus): Ursodiol (Actigall), Hydroxyzine (Atarax), Cholestyramine, Rifampicin, and Phenobarbitol have all been used to varying degrees of success.
Many patients with Alagille's Syndrome will also benefit from a high dose of a multivitamin such as ADEK (continuing high levels of vitamins A, D, E, and K), as the reduced bile flow makes it difficult to absorb and utilize these vitamins.
[edit] Surgery
Corrective surgery is sometimes needed to repair heart defects associated with Alagille Syndrome. Also, because the pulmonary arteries are often narrow in patients with Alagille syndrome, a catheterization process similar to angioplasty may be used to widen the arteries to reduce pressure on the heart's pumping valves. In moderate to severe cases, stents may be placed in the arteries to increase their diameter. Transplantation of the liver has been a successful alternative to medication in severe cases.
Recently, a procedure called partial biliary diversion has been used to significantly reduce pruritus, jaundice, and xanthomas caused by poor bile flow. A portion of the bile produced by the liver is directed through a surgically created stoma into a plastic pouch on the patient's lower right abdomen. The pouch is periodically drained as it fills with bile.
This article incorporates public domain text from The U.S. National Library of Medicine
[edit] See also
[edit] References
- ^ synd/729 at Who Named It?
- ^ Alagille D, Odièvre M, Gautier M, Dommergues JP (January 1975). "Hepatic ductular hypoplasia associated with characteristic facies, vertebral malformations, retarded physical, mental, and sexual development, and cardiac murmur". J. Pediatr. 86 (1): 63–71. PMID 803282.
- ^ Oda T, Elkahloun AG, Pike BL, et al. (1997). "Mutations in the human Jagged1 gene are responsible for Alagille syndrome". Nat. Genet. 16 (3): 235–42. doi:10.1038/ng0797-235. PMID 9207787.
- ^ Samejima H, Torii C, Kosaki R, et al. (2007). "Screening for Alagille syndrome mutations in the JAG1 and NOTCH2 genes using denaturing high-performance liquid chromatography". Genet. Test. 11 (3): 216–27. doi:10.1089/gte.2006.0519. PMID 17949281.
[edit] External links
- Official Website for the Alagille Syndrome Alliance
- Official Alagille Syndrome Alliance message board
- GeneReviews/NCBI/UW/NIH entry on Alagille syndrome
- OMIM entries on Alagille syndrome
- Alagille Syndrome, Liver Diseases and Treatments, Cincinnati Children's Hospital Medical Center
- Information from the Alagille Syndrome Alliance
|
|||||||||||||||||||||||||||||||||||||||
|
||||||||||||||
