Alagille syndrome

Source: Wikipedia, the free encyclopedia.
Alagille syndrome
Other namesAlagille–Watson syndrome (ALGS), hepatic ductular hypoplasia
Alagille syndrome is inherited in an autosomal dominant manner
SpecialtyMedical genetics, Gastroenterology, Cardiology
Named afterDaniel Alagille

Alagille syndrome (ALGS) is a genetic disorder that affects primarily the liver and the heart. 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 30,000 to 1 in every 40,000 live births. It is named after the French pediatrician Daniel Alagille, who first described the condition in 1969.[1][2]

Signs and symptoms

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 that requires

transplantation.[3] It is uncommon, but Alagille syndrome can be a life-threatening disease with a mortality rate of 10%.[4] The majority of deaths from ALGS are typically due to heart complications or chronic liver failure.[5] [citation needed
]

Liver

Signs and symptoms arising from liver damage in Alagille syndrome may include a yellowish tinge in the

Hepatocellular cancer has been reported in a small number of cases, but it is extremely rare.[8]

Heart

Tetralogy of Fallot is a common heart defect experienced in Alagille syndrome patients.

Common signs of Alagille syndrome include congenital heart problems varying from heart murmurs to significant structural abnormalities, such as

Pulmonary Stenosis, overriding aorta, ventricular septal defect, and right ventricular hypertrophy are common amongst Alagille patients. Patients may also present with Ventricular septal defect, Atrial septal defect, Patent ductus arteriosus, and Coarctation of the aorta. The mortality rate of Tetralogy of Fallot when untreated ranges from 70% by age 10 to 95% by age 40. However, complete surgical repair can significantly improve both longevity and quality of life in patients with Alagille syndrome.[citation needed
]

Other

Other presentations of Alagille's syndrome include

lipidosis caused by the hindrance of lipid metabolism.[10]

Genetics

ALGS is caused by loss of function mutations in either

autosomal dominant gene, there have been reports of a rare, autosomal recessive version of the disease.[13] In the autosomal recessive case, the ALGS patient must inherit two mutated genes: one from each parent. Although about 40% of the mutations are inherited from affected parents, most cases result from new, acquired mutations. These are caused by environmental factors that mutate one copy of the gene.[14] Environmental factors that can result in gene mutations may include radiation such as ultraviolet rays from the sun, or chemicals such as benzene, which is found in cigarette smoke.[15] These cases occur in people with no familial history of the disorder.[citation needed
]

Pathophysiology

NOTCH2 encode for proteins that are crucial to the notch gene–signaling cascade. Specifically, JAG1 encodes for a surface-binding ligand that regulates the notch signaling pathway. It plays a crucial role in cell signaling during embryonic development. If the pathway is disrupted due to mutations, an infant will not develop properly.[16] Alagille syndrome causes bile duct paucity, which is characterized by narrow and malformed bile ducts. Bile duct paucity causes bile to build up in the liver, resulting in scarring of the liver which hinders the liver's normal functions, like blood filtration and drug metabolism.[16]

The notch gene–signaling cascade is also important for cell–cell recognition, which involves gene regulation mechanisms that control multiple cell differentiation processes during embryonic and adult life, and is specially important for:[citation needed]

Diagnosis

Alagille syndrome can be extremely difficult to diagnose. While people are born with ALGS, it is almost always diagnosed later during childhood. The diagnosis can be difficult because the severity of the disease varies widely among patients.

single nucleotide polymorphisms (SNPs) in the affected gene(s). Multiplex ligation-dependent probe amplification (MLPA) can detect large deletions and/or insertions and microarray comparative genomic hybridization is used to improve the accuracy of MLPA.[18]

Treatment

Early treatment is possible once the disease is diagnosed. Treatments of Alagille syndrome typically involve medications, therapies, and/or surgical procedures. All treatments aim to improve bile excretion from the liver, reduce pain caused by the disease, and help improve nutritional deficiencies.[19] Diet can also be a crucial factor in improving quality of life when living with ALGS.[citation needed]

Medication

Several medications are used to improve bile flow, including

ursodiol or liver transplant.[19]

Many patients with Alagille syndrome have nutritional and/or malabsorption issues which often hinders normal growth. Patients benefit from vitamin A, D, E, and K supplements because the reduced bile flow makes it difficult to absorb and utilize these vitamins. A high-calorie diet is very important, and often requires a gastrostomy tube to maintain the high caloric intake.[citation needed]

Maralixibat (Livmarli) was approved for medical use in the United States in September 2021.[20][21]

Surgery

Surgery is common in more severe cases on Alagille syndrome, especially for patients with liver disease or end-stage liver failure. Liver transplants can either be a complete liver transplant from a deceased organ donor, or a partial transplant from a living donor.[22][23] Liver transplants can be difficult in ALGS patients because heart defects are common along with the liver failure, and such intense surgeries are dangerous for cardiac patients because they cannot handle the stress of surgery and general anesthesia.[citation needed]

Partial biliary diversion has been used to significantly reduce

Kasai procedure to improve bile drainage; however, later liver transplantation is still often necessary.[citation needed
]

See also

References

  1. Who Named It?
  2. PMID 803282
    .
  3. ^ "Alagille syndrome". Genetics Home Reference. Retrieved 31 October 2016.
  4. PMID 29939604. {{cite journal}}: Cite journal requires |journal= (help
    )
  5. PMID 29543694
    .
  6. ^ "Symptoms & Causes for Alagille Syndrome". National Institute of Diabetes and Digestive and Kidney Diseases.
  7. ^
    PMID 9039994
    .
  8. PMID 19706204
    .
  9. PMID 6875709
    .
  10. PMID 29318215
    .
  11. S2CID 5775213
    .
  12. PMID 22209762
    .
  13. ^
    PMID 22521120
    .
  14. ^
    S2CID 52883591
    .
  15. ^ "What is a gene mutation and how do mutations occur?". U.S. National Library of Medicine.
  16. ^ a b "Alagille syndrome". Genetics Home Reference. Retrieved 2016-12-23.
  17. ^ a b "Alagille Syndrome - Diagnosis & Treatment". Boston Children's Hospital.
  18. S2CID 24604635
    .
  19. ^ a b c "Department of Surgery - Alagille Syndrome". surgery.ucsf.edu. Retrieved 2019-10-08.
  20. ^ Highlights of prescribing information
  21. ^ "Maralixibat: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Retrieved 29 September 2021.
  22. OCLC 1111825084
    .
  23. ^ "Donor Requirements & Evaluation - Live Liver Transplant". Lahey Hospital & Medical Center, Burlington & Peabody. Retrieved 2019-10-08.

External links

Retrieved from "https://en.wikipedia.org/w/index.php?title=Alagille_syndrome&oldid=1187733246"