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| MeshID = D016738 | | | MeshID = D016738 | |
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| {{Search infobox}} | | {{Alagille syndrome}} |
| '''For patient information click [[{{PAGENAME}} (patient information)|here]]''' | | '''For patient information click [[{{PAGENAME}} (patient information)|here]]''' |
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| {{CMG}} | | {{CMG}}; '''Associate Editor-In-Chief:'''[[Sandeep Basnet| Sandeep Basnet, MBBS]], [[User: Prashanthsaddala|Prashanth Saddala M.B.B.S]] |
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| {{Editor Help}} | | {{SK}} Alagille's syndrome; Alagille-Watson syndrome; arteriohepatic dysplasia (AHD); cardiovertebral syndrome; cholestasis with peripheral pulmonary stenosis; hepatic ductular hypoplasia; hepatofacioneurocardiovertebral syndrome; paucity of interlobular bile ducts; Watson-Miller syndrome |
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| ==Overview== | | ==[[Alagille syndrome overview|Overview]]== |
| '''Alagille syndrome''' is a multisystem [[genetic disorder]] that affects the [[liver]], [[heart]], [[eyes]], [[face]], [[skeleton]], [[kidneys]] and [[vascular system]]. Problems associated with the disorder generally become evident in infancy or early childhood. The patients have a characteristic facial appearance. The disorder is inherited in an [[autosomal dominant]] pattern, and the estimated prevalence of Alagille syndrome is 1 in every 70,000 live births. The clinical features are highly variable even within the family.
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| ==Pathophysiology== | | ==[[Alagille syndrome historical perspective|Historical Perspective]]== |
| 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.
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| [[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. | | ==[[Alagille syndrome pathophysiology|Pathophysiology]]== |
| | ==[[Alagille syndrome epidemiology and demographics|Epidemiology and Demographics]]== |
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| [[NOTCH2]] is also associated with Alagille syndrome.<ref name="pmid17949281">{{cite journal |author=Samejima H, Torii C, Kosaki R, ''et al'' |title=Screening for Alagille syndrome mutations in the JAG1 and NOTCH2 genes using denaturing high-performance liquid chromatography |journal=Genet. Test. |volume=11 |issue=3 |pages=216–27 |year=2007 |pmid=17949281 |doi=10.1089/gte.2006.0519}}</ref> | | ==[[Alagille syndrome risk factors|Risk Factors]]== |
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| 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.
| | ==[[Alagille syndrome causes|Causes]]== |
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| Children with Alagille syndrome may be at risk for pathologic fractures, which manifest at an early age and in a unique distribution favoring the lower extremity long bones <ref name="pmid20453673">{{cite journal| author=Bales CB, Kamath BM, Munoz PS, Nguyen A, Piccoli DA, Spinner NB et al.| title=Pathologic lower extremity fractures in children with Alagille syndrome. | journal=J Pediatr Gastroenterol Nutr | year= 2010 | volume= 51 | issue= 1 | pages= 66-70 | pmid=20453673 | doi=10.1097/MPG.0b013e3181cb9629 | pmc=PMC2893241 | url= }} </ref>.
| | ==[[Alagille syndrome differential diagnosis|Differentiating Alagille syndrome from Other Diseases]]== |
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| ==Associated Conditions== | | ==[[Alagille syndrome natural history|Natural History, Complications & Prognosis]]== |
| 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== |
| | | [[Alagille syndrome diagnostic criteria|Diagnostic Criteria]] | [[Alagille syndrome history and symptoms | History and Symptoms]] | [[Alagille syndrome physical examination | Physical Examination]] | [[Alagille syndrome laboratory findings | Laboratory Findingd]] | [[Alagille syndrome electrocardiogram |Electrocardiogram]] | [[Alagille syndrome x ray|X Ray]] | [[Alagille syndrome CT|CT]] | [[Alagille syndrome MRI|MRI]] | [[Alagille syndrome other imaging findings |Other Imaging Findings]] | [[Alagille syndrome other diagnostic studies|Other Diagnostic Studies]] |
| ==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]].
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| ===Symptoms===
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| *[[Itching]]
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| ===Physical Examination===
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| ====Head, Eyes, Ears, Nose, Throat====
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| *A broad, prominent forehead, deep-set eyes, and a small pointed chin may be present.
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| *[[Scleral icterus]]
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| ====Skin====
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| *[[Jaundice]]
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| *[[Xanthomas]]
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| ===Laboratory Studies===
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| ====Biochemical Evaluation====
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| Total Bilirubin >6.5 mg/dL, Conjugated Bilirubin >4.5 mg/dL, and cholesterol >520 mg/dL in children younger than 5 years of age are likely be associated with severe liver disease in later life <ref name="pmid20421762">{{cite journal| author=Kamath BM, Munoz PS, Bab N, Baker A, Chen Z, Spinner NB et al.| title=A longitudinal study to identify laboratory predictors of liver disease outcome in Alagille syndrome. | journal=J Pediatr Gastroenterol Nutr | year= 2010 | volume= 50 | issue= 5 | pages= 526-30 | pmid=20421762 | doi=10.1097/MPG.0b013e3181cea48d | pmc=PMC2861305 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20421762 }} </ref>.
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| ====Liver Biopsy====
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| A liver [[biopsy]] may indicate too few [[bile duct]]s (bile duct paucity).
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| ====X ray====
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| An unusual butterfly shape of the bones of the spinal column that can be seen in an [[x-ray]]
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| ==Treatment== | | ==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.
| | [[Alagille syndrome medical therapy|Medical Therapy]] | [[Alagille syndrome surgery|Surgery]] | [[Alagille syndrome cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Alagille syndrome future or investigational therapies|Future or Investigational Therapies]] |
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| ==Medical Therapy==
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| The medical management of Alagille Syndrome is complex and continues to generate controversy. The significant variability of organ involvement requires the managing physician to have an understanding of the breadth and interplay of the variable manifestations. Furthermore, the liver disease in particular requires an appreciation of the natural history and evolution of the profound cholestasis.
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| 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.
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| 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.
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| ==Surgery==
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| Corrective surgery is sometimes needed to repair heart defects associated with Allagile Syndrome. Also, because the pulmonary arteries are often narrow in Alagille 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. However, liver transplantation from donor parents should always be preceded by genetic testing because cases have been known where donor mother was also found to have alagille syndrome post transplant owing to the autosomal dominant inheritance pattern of the syndrome. Death from graft failure, neurological, and cardiac complications is significantly higher in patients with Alagille Syndrome than patients with Biliary Atresia <ref name="pmid20070561">{{cite journal| author=Arnon R, Annunziato R, Miloh T, Suchy F, Sakworawich A, Sogawa H et al.| title=Orthotopic liver transplantation for children with Alagille syndrome. | journal=Pediatr Transplant | year= 2010 | volume= 14 | issue= 5 | pages= 622-8 | pmid=20070561 | doi=10.1111/j.1399-3046.2009.01286.x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20070561 }} </ref>.
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| 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.
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| The Kasai procedure, although appropriate for children with biliary atresia, does not benefit children with Alagille Syndrome and actually appears to worsen outcome <ref name="pmid20601899">{{cite journal| author=Kaye AJ, Rand EB, Munoz PS, Spinner NB, Flake AW, Kamath BM| title=Effect of Kasai procedure on hepatic outcome in Alagille syndrome. | journal=J Pediatr Gastroenterol Nutr | year= 2010 | volume= 51 | issue= 3 | pages= 319-21 | pmid=20601899 | doi=10.1097/MPG.0b013e3181df5fd8 | pmc= | url= }} </ref>.
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| ==See also== | | ==Related Chapters== |
| *[[Progressive familial intrahepatic cholestasis]] | | *[[Progressive familial intrahepatic cholestasis]] |
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| ==References==
| | {{Congenital malformations and deformations of digestive system}} |
| {{Reflist|2}} | | [[fr:Syndrome d'Alagille]] |
| | [[pl:Zespół Alagille'a]] |
| | [[pt:Síndrome de Alagille]] |
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| ==External links ==
| | {{WikiDoc Help Menu}} |
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| *[http://www.cincinnatichildrens.org/svc/alpha/l/liver/diseases/alagille-syndrome.htm Alagille Syndrome, Liver Diseases and Treatments, Cincinnati Children's Hospital Medical Center]
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| ==Support groups ==
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| *[http://www.alagille.org/ Alagille Syndrome Alliance]
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| *[http://www.liverfamilies.org/ LIVER FAMILIES: An online support group for families whose lives have been touched by pediatric liver disease and transplant. ]
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| {{Congenital malformations and deformations of digestive system}} | |
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| [[Category:Pediatrics]] | | [[Category:Pediatrics]] |
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| [[Category:Rare diseases]] | | [[Category:Rare diseases]] |
| [[Category:Hepatology]] | | [[Category:Hepatology]] |
| [[Category:Mature chapter]] | | [[Category:Overview complete]] |
| [[Category:Up-To-Date]]
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| [[de:Alagille-Syndrom]]
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| [[fr:Syndrome d'Alagille]]
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| [[nl:Syndroom van Alagille]]
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| [[pl:Zespół Alagille'a]]
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| [[pt:Síndrome de Alagille]]
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| {{WikiDoc Help Menu}}
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| {{WikiDoc Sources}}
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