Alagille syndrome: Difference between revisions
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'''Alagille syndrome''' is a [[genetic disorder]] that affects the [[liver]], [[heart]], 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 70,000 live births. | '''Alagille syndrome''' is a [[genetic disorder]] that affects the [[liver]], [[heart]], 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 70,000 live births. | ||
== | ==Associated Conditions== | ||
Alagille syndrome can be associated with [[congenital heart disease]], particularly [[Tetralogy of Fallot]]. The [[kidney]]s and [[central nervous system]] may also be affected. | |||
==Diagnosis== | |||
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]]. | 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]]. | ||
===Symptoms=== | |||
*[[Itching]] | |||
===Physical Examination== | |||
====Head, Eyes, Ears, Nose, Throat==== | |||
*A broad, prominent forehead, deep-set eyes, and a small pointed chin may be present. | |||
*[[Scleral icterus]] | |||
====Skin==== | |||
*[[Jaundice]] | |||
*[[Xanthomas]] | |||
===Laboratory Studies=== | |||
====Liver Biopsy==== | |||
A liver [[biopsy]] may indicate too few [[bile duct]]s (bile duct paucity). | |||
====X ray==== | |||
An unusual butterfly shape of the bones of the spinal column that can be seen in an [[x-ray]] | |||
==Pathophysiology== | |||
[[Mutation]]s in the [[JAG1]] [[gene]] cause Alagille syndrome.<ref name="pmid9207787">{{cite journal |author=Oda T, Elkahloun AG, Pike BL, ''et al'' |title=Mutations in the human Jagged1 gene are responsible for Alagille syndrome |journal=Nat. Genet. |volume=16 |issue=3 |pages=235–42 |year=1997 |pmid=9207787 |doi=10.1038/ng0797-235}}</ref> The JAG1 gene is involved in signaling between adjacent cells during [[Mammalian embryogenesis|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, and certain facial features. | [[Mutation]]s in the [[JAG1]] [[gene]] cause Alagille syndrome.<ref name="pmid9207787">{{cite journal |author=Oda T, Elkahloun AG, Pike BL, ''et al'' |title=Mutations in the human Jagged1 gene are responsible for Alagille syndrome |journal=Nat. Genet. |volume=16 |issue=3 |pages=235–42 |year=1997 |pmid=9207787 |doi=10.1038/ng0797-235}}</ref> The JAG1 gene is involved in signaling between adjacent cells during [[Mammalian embryogenesis|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, and certain facial features. | ||
Revision as of 21:10, 13 September 2011
| Alagille syndrome | |
| ICD-10 | Q44.7 (EUROCAT Q44.71) |
|---|---|
| ICD-9 | 759.89 |
| OMIM | 118450 |
| DiseasesDB | 29085 |
| MeSH | D016738 |
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Overview
Alagille syndrome is a genetic disorder that affects the liver, heart, 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 70,000 live births.
Associated Conditions
Alagille syndrome can be associated with congenital heart disease, particularly Tetralogy of Fallot. The kidneys and central nervous system may also be affected.
Diagnosis
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.
Symptoms
=Physical Examination
Head, Eyes, Ears, Nose, Throat
- A broad, prominent forehead, deep-set eyes, and a small pointed chin may be present.
- Scleral icterus
Skin
Laboratory Studies
Liver Biopsy
A liver biopsy may indicate too few bile ducts (bile duct paucity).
X ray
An unusual butterfly shape of the bones of the spinal column that can be seen in an x-ray
Pathophysiology
Mutations in the JAG1 gene cause Alagille syndrome.[1] 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, and certain facial features.
NOTCH2 is also associated with Alagille syndrome.[2]
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.
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.
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.
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 (contining high levels of vitamins A, D, E, and K), as the reduced bile flow makes it difficult to absorb and utilize these vitamins.
Surgery
Corrective surgery is sometimes needed to repair heart defects associated with Allagile's Syndrome. Also, because the pulmonary arteries are often narrow in Alagilles patients, 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
See also
References
- ↑ 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.
External links
Support groups
Template:SIB Template:Congenital malformations and deformations of digestive system