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Disease Profile
Alagille syndrome
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
Unknown
Age of onset
All ages
ICD-10
Q44.7
Inheritance
Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.
Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.
X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.
X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.
Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.
Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.
Not applicable
Other names (AKA)
Hepatic ductular hypoplasia; Watson Alagille syndrome; Alagille-Watson syndrome;
Categories
Congenital and Genetic Diseases
Summary
Alagille
Alagille syndrome is caused by changes or
Symptoms
- Liver problems: One of the major features of Alagille syndrome is liver damage caused by abnormalities in the bile ducts. These ducts carry bile, which helps to digest fats, from the liver to the gallbladder and small intestine. In Alagille syndrome, the bile ducts may be narrow, malformed, and reduced in number. This results in a build-up of bile causing scarring that prevents the liver from working properly. This may lead to
jaundice , itchy skin, and deposits of cholesterol in the skin (xanthomas). - Nutrition problems: Since bile is important for the digestion and absorption of fat and fat-soluble vitamins, people with Alagille syndrome may have a hard time getting enough calories and may develop Vitamin A, D, E and/or K deficiencies. Calcium and zinc deficiencies may also be associated with Alagille syndrome. Many people with Alagille syndrome continue to have nutrition problems even after a liver transplant, suggesting that other factors of the syndrome may play a role. Malnutrition can lead to slow growth, delayed puberty and other health concerns.
- Heart problems: Alagille syndrome is also associated with several heart problems, including impaired blood flow from the heart into the lungs (pulmonic stenosis). Other associated heart-related problems include a hole between the two lower chambers of the heart (ventricular septal defect) and a combination of heart defects called tetralogy of Fallot.
- Distinctive facial features: People with Alagille syndrome may have distinctive facial features, such as a broad, prominent forehead; deep-set eyes; and a small, pointed chin.
- Neurologic problems: Some people with Alagille syndrome may have
intellectual disabilities anddevelopmental delay . - Vascular problems: Alagille syndrome can be associated with abnormalities of the blood vessels in the head and neck, which can lead to spontaneous or injury-induced bleeding in the skull or brain, or a stroke. Alagille syndrome can also cause narrowing (stenosis) or bulging (aneurysm) of other blood vessels in the body.
- Kidney problems: Some children may have impaired kidney function such as kidney artery stenosis, lipoid nephrosis, or glomerulosclerosis.
- Bone problems: People may have an unusual butterfly shape of the bones of the spinal column (vertebrae) but this shape almost never causes any problems with the function of the nerves in the spinal cord. However, Vitamin D deficiency can lead to rickets or weakened bones and poor growth. Calcium deficiency and other features of Alagille syndrome can also lead to poor growth, abnormally shaped bones, and increased risk of broken bones.
- Eye problems: Eye abnormalities are common in Alagille syndrome, but for the most part do not require treatment and do not cause vision loss. The most common eye finding is an extra, circular line on the surface of the eye, called a posterior embryotoxon, that can be detected during a specialized eye examination. Although about 90% of people with Alagille syndrome have this eye finding, so do up to 15% of people who do not have this syndrome. Other eye findings may include Axenfeld anomaly, in which strands of the colored part of the eye (iris) are abnormally attached to the cornea, and color changes of the retina (retinal pigmentary changes).
- Pancreatic insufficiency: Alagille syndrome can cause pancreatic insufficiency. People whose pancreas does not produce enough
enzymes to help digest food do not properly absorb fat from food (fat malabsorption) and excrete fat in their bowel movements. Pancreatic insufficiency can cause poor nutrition and growth and therefore is believed to play a larger role than first suspected in the nutritional problems for people with Alagille syndrome.
More information about the symptoms associated with Alagille syndrome can be found on the Children's Hospital of Philadelphia (CHOP) Alagille Syndrome information page and GeneReviews Alagille Syndrome Report.
This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.
Medical Terms | Other Names |
Learn More:
HPO ID
|
---|---|---|
80%-99% of people have these symptoms | ||
Cholestasis |
Slowed or blocked flow of bile from liver
|
0001396 |
Corneal dystrophy | 0001131 | |
Failure to thrive |
Faltering weight
Weight faltering
[ more ] |
0001508 |
Hepatomegaly |
Enlarged liver
|
0002240 |
Reduced number of intrahepatic bile ducts | 0006571 | |
Ventricular septal defect |
Hole in heart wall separating two lower heart chambers
|
0001629 |
30%-79% of people have these symptoms | ||
Butterfly vertebral arch | 0004617 | |
Coarse facial features |
Coarse facial appearance
|
0000280 |
Frontal bossing | 0002007 | |
Intrauterine growth retardation |
Prenatal growth deficiency
Prenatal growth retardation
[ more ] |
0001511 |
Long nose |
Elongated nose
Increased height of nose
Increased length of nose
Increased nasal height
Increased nasal length
Nasal elongation
[ more ] |
0003189 |
Pointed chin |
Pointy chin
Small pointed chin
Witch's chin
[ more ] |
0000307 |
Protruding ear |
Prominent ear
Prominent ears
[ more ] |
0000411 |
Round face |
Circular face
Round facial appearance
Round facial shape
[ more ] |
0000311 |
Spina bifida occulta | 0003298 | |
Telangiectasia of the skin | 0100585 | |
Vertebral segmentation defect | 0003422 | |
5%-29% of people have these symptoms | ||
Abnormal pupil morphology |
Abnormality of the pupil
Pupillary abnormalities
Pupillary abnormality
[ more ] |
0000615 |
Abnormality of the ribs |
Rib abnormalities
|
0000772 |
Abnormality of the ureter | 0000069 | |
Atrial septal defect |
An opening in the wall separating the top two chambers of the heart
Hole in heart wall separating two upper heart chambers
[ more ] |
0001631 |
Brachycephaly |
Short and broad skull
|
0000248 |
Clinodactyly of the 5th finger |
Permanent curving of the pinkie finger
|
0004209 |
Cryptorchidism |
Undescended testes
Undescended testis
[ more ] |
0000028 |
Deeply set eye |
Deep set eye
Deep-set eyes
Sunken eye
[ more ] |
0000490 |
Delayed puberty |
Delayed pubertal development
Delayed pubertal growth
Pubertal delay
[ more ] |
0000823 |
Delayed skeletal maturation |
Delayed bone maturation
Delayed skeletal development
[ more ] |
0002750 |
Downslanted palpebral fissures |
Downward slanting of the opening between the eyelids
|
0000494 |
Flat face |
Flat facial shape
|
0012368 |
Hypertelorism |
Wide-set eyes
Widely spaced eyes
[ more ] |
0000316 |
0000822 | ||
Hypoplasia of the ulna |
Underdeveloped inner large forearm bone
|
0003022 |
Intellectual disability, mild |
Mental retardation, borderline-mild
Mild and nonprogressive mental retardation
Mild mental retardation
[ more ] |
0001256 |
Keratoconus |
Bulging cornea
|
0000563 |
Little lower jaw
Small jaw
Small lower jaw
[ more ] |
0000347 | |
Nephrotic syndrome | 0000100 | |
Peripheral pulmonary artery stenosis |
Narrowing of peripheral lung artery
|
0004969 |
Renal hypoplasia/aplasia |
Absent/small kidney
Absent/underdeveloped kidney
[ more ] |
0008678 |
Short distal phalanx of finger |
Short outermost finger bone
|
0009882 |
Short philtrum | 0000322 | |
Specific learning disability | 0001328 | |
Cross-eyed
Squint
Squint eyes
[ more ] |
0000486 | |
1%-4% of people have these symptoms | ||
Duplicated collecting system | 0000081 | |
Focal segmental glomerulosclerosis | 0000097 | |
Hepatic failure |
Liver failure
|
0001399 |
Conditions with similar signs and symptoms from Orphanet
|
---|
Differential diagnoses include biliary atresia, congenital hepatic fibrosis, cystic fibrosis, neonatal jaundice, polycystic kidney disease, progressive familial intrahepatic cholestasis, and tyrosinemia (see these terms).
Visit the Orphanet disease page for more information.
|
Organizations
Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.
Organizations Supporting this Disease
-
Alagille Syndrome Alliance (ALGSA)
PO Box 4216
Wilsonville, OR 97070
Telephone: 503-970-1255
E-mail: alagille@alagille.org
Website: https://alagille.org -
Children's Liver Disease Foundation
36 Great Charles Street
Birmingham, B3 3JY
United Kingdom
Telephone: +44 (0) 121 212 3839
Fax: +44 (0) 121 212 4300
E-mail: info@childliverdisease.org
Website: https://www.childliverdisease.org/ -
Children’s Liver Association for Support Services
25379 Wayne Mills Place, Suite 143
Valencia, CA 91355
Telephone: 1–877–679–8256
Fax: 661–263–9099
E-mail: info@classkids.org
Website: https://www.classkids.org
Organizations Providing General Support
-
American Liver Foundation
39 Broadway, Suite 2700
New York, NY 10006
Toll-free: +1-800-465-4837 (Helpline)
Telephone: +1-212-668-1000
E-mail: https://liverfoundation.org/for-patients/contact-us/
Website: https://liverfoundation.org/
Learn more
These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.
Where to Start
- The American Liver Foundation provides information about Alagille syndrome. Click on the above link to view this information.
- Genetics Home Reference (GHR) contains information on Alagille syndrome. This website is maintained by the National Library of Medicine.
- The National Digestive Diseases Information Clearinghouse (NIDDK) offers information on this condition. Click on the link to view information on this topic.
- The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.
In-Depth Information
- GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
- Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
- The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
- Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
- Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
- PubMed is a searchable database of medical literature and lists journal articles that discuss Alagille syndrome. Click on the link to view a sample search on this topic.
References
- Alagille Syndrome. https://www.albireopharma.com/programs/a4250. January, 2019; https://digestive.niddk.nih.gov/ddiseases/pubs/alagille/.
- Alagille Syndrome. American Liver Foundation. https://www.liverfoundation.org/abouttheliver/info/alagille/.
- Alagille syndrome. Genetics Home Reference (GHR). 2014; https://ghr.nlm.nih.gov/condition=alagillesyndrome.
- Spinner NB, Hitchinson AL, Krantz ID, Kamath BM. Alagille Syndrome. GeneReviews. 2013; https://www.ncbi.nlm.nih.gov/books/NBK1273/.
- Alagille Syndrome. Children's Hospital of Pennsylvania (CHOP). https://www.chop.edu/conditions-diseases/alagille-syndrome.
- Berniczei-Royko A & cols. Medical and dental management of Alagille syndrome: A review. Med Sci Monit. 2014; 20:476-480. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3972053/pdf/medscimonit-20-476.pdf.
- Ramachandran P & cols. Outcome of partial internal biliary diversion for intractable pruritus in children with cholestatic liver disease. Pediatr Surg Int. 2014; 30(10):1045-9. https://www.ncbi.nlm.nih.gov/pubmed/25064227.
- Ben Ameur S, Chabchoub I, Telmoudi J & cols. Management of cholestatic pruritus in children with Alagille syndrome: Case report and literature review. Arch Pediatr. 2016; 23(12):1247-1250. https://www.ncbi.nlm.nih.gov/pubmed/28492167.
- Scheimann A. Alagille Syndrome. Medscape Reference. January 10, 2016; https://reference.medscape.com/article/926678-overview.
- Smithson S. Treatment of cardiovascular complications of Alagille syndrome in clinical optimization for liver transplantation. International Journal of Cardiology. 2014; 176(2):37-40. https://www.internationaljournalofcardiology.com/article/S0167-5273(14)00869-9/fulltext.
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