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Indian Journal of Pediatrics Sep 2002Alagille syndrome (AGS) was described more than 35 years ago as a genetic entity characterised by five major features: chronic cholestasis owing to paucity of... (Review)
Review
Alagille syndrome (AGS) was described more than 35 years ago as a genetic entity characterised by five major features: chronic cholestasis owing to paucity of interlobular bile ducts; peripheral pulmonary stenosis; butterfly like vertebral arch defect; posterior embryotoxon and peculiar facies. AGS has long been said to have a relative good prognosis but overall survival at twenty years averages 70%. Complex congenital heart disease and hepatic disease with or without liver transplantation contribute significantly to mortality. JAGGED1 has been identified as a responsible gene by demonstration of mutations in AGS patients. Studies of JAGGED1 expression pattern demonstrate that minor features and almost all the elements in the long list of manifestations described in AGS patients are not coincidental. This suggests that Alagille syndrome definition may be revisited in the light of JAGGED1 mutations.
Topics: Alagille Syndrome; Child; Child, Preschool; Disease Progression; Female; Humans; Incidence; India; Infant; Infant, Newborn; Male; Risk Factors; Survival Rate
PubMed: 12420916
DOI: 10.1007/BF02723697 -
Indian Journal of Pediatrics Sep 2002Syndromic paucity of bile ducts or "Alagille syndrome" is characterized by peculiar facies, chronic cholestasis, posterior embryotoxon, butterfly-like vertebral arch... (Review)
Review
Syndromic paucity of bile ducts or "Alagille syndrome" is characterized by peculiar facies, chronic cholestasis, posterior embryotoxon, butterfly-like vertebral arch defects and peripheral pulmonary artery hypoplasia or stenosis. We present a two-year-old female child with the 'partial' or 'incomplete' Alagille syndrome. The child had three of the five major features of the syndrome. A brief review of literature of the syndrome is presented.
Topics: Alagille Syndrome; Child, Preschool; Disease Progression; Female; Follow-Up Studies; Humans; India; Liver Function Tests; Risk Assessment; Severity of Illness Index
PubMed: 12420920
DOI: 10.1007/BF02723701 -
Clinical and Investigative Medicine.... Oct 1996A genetic syndrome causing paucity of interlobular bile ducts (Alagille syndrome) is characterized by five main characteristics: typical, peculiar facies; chronic... (Review)
Review
A genetic syndrome causing paucity of interlobular bile ducts (Alagille syndrome) is characterized by five main characteristics: typical, peculiar facies; chronic cholestasis; posterior embryotoxon; butterfly-like vertebral-arch defects; and cardiovascular malformations. In the complete form of the syndrome, all five features are observed. Four or less of these characteristics are present in the incomplete or partial forms of this syndrome. Other, less frequent characteristics (growth retardation, mental retardation, renal and bone abnormalities as well as a high-pitched voice) have also been observed. An autosomal dominant mode of genetic transmission with variable penetrance seems likely. Therapy consists of nutritional supplementation of medium-chain triglycerides, essential fatty acids and fat-soluble vitamins. Liver transplantation has been used successfully to treat patients with liver failure, portal hypertension or severe pruritus and xanthomatosis.
Topics: Alagille Syndrome; Humans
PubMed: 8889270
DOI: No ID Found -
Fetal and Pediatric Pathology Feb 2021This review aims to highlight the clinicopathological characteristics and differential diagnosis of central hepatic regenerative nodules (CHRNs) in patients with... (Review)
Review
OBJECTIVE
This review aims to highlight the clinicopathological characteristics and differential diagnosis of central hepatic regenerative nodules (CHRNs) in patients with Alagille syndrome.
METHODS
A review of the literature for cases of CHRNs and their differential diagnoses in patients with Alagille syndrome was performed and the main findings were collated.
RESULTS
Large, regenerative hepatic nodules are seen in approximately 30% of patients with Alagille syndrome. They are thought to be a functional adaptation to vascular changes rather than a neoplastic process. The nodules are typically centrally located, and normal hepatic vasculature coursing through the lesions are noted radiologically. Microscopically, they are characterized by well-circumscribed hepatic lesions with preserved architecture, lesser degrees of fibrosis and relative preservation of interlobular bile ducts compared to the background cirrhotic liver.
CONCLUSION
Regenerative nodules are common in Alagille's syndrome, and should be distinguished from hepatocellular carcinomas and adenomas for appropriate management and prognostication.
Topics: Alagille Syndrome; Carcinoma, Hepatocellular; Diagnosis, Differential; Humans; Liver; Liver Neoplasms
PubMed: 31608763
DOI: 10.1080/15513815.2019.1675834 -
Journal of Pediatric Gastroenterology... Jan 2010Alagille syndrome is a multisystem disorder in which progressive liver disease with persistent cholestasis and dramatic pruritus often warrant consideration for liver... (Review)
Review
Alagille syndrome is a multisystem disorder in which progressive liver disease with persistent cholestasis and dramatic pruritus often warrant consideration for liver transplantation. The most important part of the transplant assessment is evaluation of the cardiac and renal involvement. Preoperatively, cardiac performance often must be tested with dynamic stress tests, mimicking hemodynamic changes during liver transplant. Many aspects of the syndrome including cholestasis, pruritus, and hypercholesterolemia improve posttransplant, but short stature is rarely significantly affected. One- and 5-year patient and graft survival after liver transplant is comparable to other elective indications, but effects of long-term immunosuppressants on evolution of other components of the syndrome, including vascular, bone, and renal disease, remain largely unknown.
Topics: Alagille Syndrome; Graft Survival; Humans; Immunosuppressive Agents; Liver Transplantation; Preoperative Care
PubMed: 19949348
DOI: 10.1097/MPG.0b013e3181c1601f -
Revista Espanola de Enfermedades... Apr 2019Alagille syndrome (ALGS) is an autosomal-dominant multisystem disorder caused by mutations in Jagged 1 (JAG1) or NOTCH2. The penetrance is low but highly variable. It is... (Review)
Review
Alagille syndrome (ALGS) is an autosomal-dominant multisystem disorder caused by mutations in Jagged 1 (JAG1) or NOTCH2. The penetrance is low but highly variable. It is almost exclusively diagnosed in children with cholestasis and, more rarely, in their adult relatives. Here, we report the case of a patient diagnosed with ALGS in adulthood. The patient was a 28-year-old male who presented with characteristic facial features, an eye abnormality, chronic cholestasis with bile duct paucity on liver biopsy, atrial defects and stenosis of the left internal carotid artery. A novel frameshift mutation, c.2087_2088insAAAAATGG (p. W697Kfs*49), in JAG1 was identified. To our knowledge, this is the first case of ALGS diagnosed in adulthood in China. ALGS should be considered as a differential diagnosis for intrahepatic cholestasis in adult patients with a wide variety of clinical manifestations, including cardiac disease, skeletal abnormalities, ocular abnormalities and characteristic facial features.
Topics: Adult; Alagille Syndrome; Bile Ducts; Carotid Stenosis; Cholestasis, Intrahepatic; Frameshift Mutation; Humans; Jagged-1 Protein; Magnetic Resonance Imaging; Male; Tomography, X-Ray Computed
PubMed: 30746957
DOI: 10.17235/reed.2019.5679/2018 -
Seminars in Liver Disease Nov 2001Since the first descriptions of Alagille syndrome (syndromic bile duct paucity) 30 years ago, our appreciation of the clinical variability and complexity of this... (Review)
Review
Since the first descriptions of Alagille syndrome (syndromic bile duct paucity) 30 years ago, our appreciation of the clinical variability and complexity of this disorder has grown. In addition to the liver, Alagille syndrome is associated with abnormalities that involve the heart, eye, skeleton, kidneys, and the increasing importance of abnormalities of the central nervous system is being recognized. The developmental nature of the disorder has been proven with the identification of the disease-causing gene, Jagged1. Jagged1 is a cell surface protein that functions in an embryologically important signaling pathway, known as the Notch signaling pathway. Identification of the role of Jagged1 (JAG1) in the etiology of Alagille syndrome has improved diagnosis for this variably expressed disorder. In this review, we summarize information on the range of clinical abnormalities of the liver and other affected organs in affected individuals. Genetic studies have demonstrated the range of defects in JAG1 that cause Alagille syndrome. Mutations in JAG1 can be identified in 70% of Alagille syndrome patients, and they are inherited in 30-50%. These mutations include total gene deletions as well as mutations (frameshift, missense, and nonsense) in almost all regions of the 26 exons of the Jagged1 gene. This review focuses on clinical and genetic features of Alagille syndrome.
Topics: Alagille Syndrome; Calcium-Binding Proteins; Humans; Intercellular Signaling Peptides and Proteins; Jagged-1 Protein; Membrane Proteins; Mutation; Proteins; Serrate-Jagged Proteins
PubMed: 11745040
DOI: 10.1055/s-2001-19036 -
Hepatology (Baltimore, Md.) Jun 2024Alagille syndrome (ALGS) is characterized by chronic cholestasis with associated pruritus and extrahepatic anomalies. Maralixibat, an ileal bile acid transporter... (Comparative Study)
Comparative Study
BACKGROUND AND AIMS
Alagille syndrome (ALGS) is characterized by chronic cholestasis with associated pruritus and extrahepatic anomalies. Maralixibat, an ileal bile acid transporter inhibitor, is an approved pharmacologic therapy for cholestatic pruritus in ALGS. Since long-term placebo-controlled studies are not feasible or ethical in children with rare diseases, a novel approach was taken comparing 6-year outcomes from maralixibat trials with an aligned and harmonized natural history cohort from the G lobal AL agille A lliance (GALA) study.
APPROACH AND RESULTS
Maralixibat trials comprise 84 patients with ALGS with up to 6 years of treatment. GALA contains retrospective data from 1438 participants. GALA was filtered to align with key maralixibat eligibility criteria, yielding 469 participants. Serum bile acids could not be included in the GALA filtering criteria as these are not routinely performed in clinical practice. Index time was determined through maximum likelihood estimation in an effort to align the disease severity between the two cohorts with the initiation of maralixibat. Event-free survival, defined as the time to first event of manifestations of portal hypertension (variceal bleeding, ascites requiring therapy), surgical biliary diversion, liver transplant, or death, was analyzed by Cox proportional hazards methods. Sensitivity analyses and adjustments for covariates were applied. Age, total bilirubin, gamma-glutamyl transferase, and alanine aminotransferase were balanced between groups with no statistical differences. Event-free survival in the maralixibat cohort was significantly better than the GALA cohort (HR, 0.305; 95% CI, 0.189-0.491; p <0.0001). Multiple sensitivity and subgroup analyses (including serum bile acid availability) showed similar findings.
CONCLUSIONS
This study demonstrates a novel application of a robust statistical method to evaluate outcomes in long-term intervention studies where placebo comparisons are not feasible, providing wide application for rare diseases. This comparison with real-world natural history data suggests that maralixibat improves event-free survival in patients with ALGS.
Topics: Humans; Alagille Syndrome; Female; Male; Retrospective Studies; Child; Infant; Child, Preschool; Progression-Free Survival; Adolescent; Carrier Proteins; Membrane Glycoproteins
PubMed: 38146932
DOI: 10.1097/HEP.0000000000000727 -
Clinics in Liver Disease May 2013Neonatal conjugated jaundice is a common presentation of hereditary liver diseases, which, although rare, are important to recognize early. Developments in molecular... (Review)
Review
Neonatal conjugated jaundice is a common presentation of hereditary liver diseases, which, although rare, are important to recognize early. Developments in molecular genetic techniques have enabled the identification of causative genes, which has improved diagnostic accuracy for patients and has led to a greater understanding of the molecular pathways involved in liver biology and pathogenesis of liver diseases. This review provides an update of the current understanding of clinical and molecular features of the inherited liver diseases that cause neonatal conjugated jaundice.
Topics: Alagille Syndrome; Cholestasis; Humans; Prognosis
PubMed: 23540503
DOI: 10.1016/j.cld.2012.12.004 -
Medicina Clinica Mar 2022
Topics: Adult; Alagille Syndrome; Carcinoma, Hepatocellular; Humans; Liver Cirrhosis; Liver Neoplasms
PubMed: 34256939
DOI: 10.1016/j.medcli.2021.06.010