Liver Disease in Alagille Syndrome

Kriegermeier, Alyssa; Wehrman, Andrew; Kamath, Binita M.; Loomes, Kathleen M.

doi:10.1007/978-3-319-94571-2_4

Cited by 4 publications

(4 citation statements)

References 56 publications

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“…The classic clinical feature of ALGS is neonatal cholestasis with high gamma-glutamyl transferase, which is present in 85% and is associated with pruritus in 74% of patients [ 6 ]. Complications secondary to cholestasis are burdensome in early childhood and include fat-soluble vitamin deficiency (FSVD), growth failure, and disfiguring xanthomas [ 7 ]. In the current era with readily available genetic testing, a liver biopsy is no longer necessary for the diagnosis of ALGS.…”

Section: Features Of Alagille Syndrome and Relevance In Adulthoodmentioning

confidence: 99%

“…However, cardiac defects may be identified for the first time in adulthood, which if associated with liver involvement, should raise suspicion for ALGS. Finally, the hyperlipidemia associated with cholestatic ALGS is predominantly lipoprotein X which has no atherosclerotic consequences [ 7 ]. The implications of cardiac defects on LT candidacy will be discussed further below.…”

Section: Features Of Alagille Syndrome and Relevance In Adulthoodmentioning

confidence: 99%

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Management of adults with Alagille syndrome

et al. 2023

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Alagille syndrome (ALGS) is a complex rare genetic disorder that involves multiple organ systems and is historically regarded as a disease of childhood. Since it is inherited in an autosomal dominant manner in 40% of patients, it carries many implications for genetic counselling of patients and screening of family members. In addition, the considerable variable expression and absence of a clear genotype–phenotype correlation, results in a diverse range of clinical manifestations, even in affected individuals within the same family. With recent therapeutic advancements in cholestasis treatment and the improved survival rates with liver transplantation (LT), many patients with ALGS survive into adulthood. Although LT is curative for liver disease secondary to ALGS, complications secondary to extrahepatic involvement remain problematic lifelong. This review is aimed at providing a comprehensive review of ALGS to adult clinicians who will take over the medical care of these patients following transition, with particular focus on certain aspects of the condition that require lifelong surveillance. We also provide a diagnostic framework for adult patients with suspected ALGS and highlight key aspects to consider when determining eligibility for LT in patients with this syndrome.

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Section: Features Of Alagille Syndrome and Relevance In Adulthoodmentioning

confidence: 99%

Section: Features Of Alagille Syndrome and Relevance In Adulthoodmentioning

confidence: 99%

Management of adults with Alagille syndrome

et al. 2023

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“…In a majority, the mutations in the JAG1 gene are protein truncations, others include gene deletions and missense mutations. 2 , 6 Of all the organs involved, ALGS affects the liver and the heart the most. Jagged1 expression in the portal vein mesenchyme is necessary for bile duct formation.…”

Section: Genetics and Pathogenesis Of Algsmentioning

confidence: 99%

“… 1 It is caused by mutations involving the notch signaling pathway of either the JAG1 gene (encoding JAGGED) (94–99%) located on chromosome 20 or the NOTCH2 gene (1–4%) located on chromosome 1. 1 , 2 Although traditionally labeled as arteriohepatic dysplasia confined to the liver, this disease affects multiple organs. With an appreciation of increasing numbers of phenotypes, a revised set of diagnostic criteria for ALGS has been proposed.…”

Section: Introductionmentioning

confidence: 99%

Multidisciplinary Management of Alagille Syndrome

Menon¹,

Shanmugam²,

Vij³

et al. 2022

JMDH

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Alagille syndrome (ALGS) is an autosomal dominant disorder characterized by involvement of various organ systems. It predominantly affects the liver, skeleton, heart, kidneys, eyes and major blood vessels. With myriads of presentations across different age groups, ALGS is usually suspected in infants presenting with high gamma glutamyl transpeptidase cholestasis and/or congenital heart disease. In children it may present with decompensated cirrhosis, intellectual disability or short stature, and in adults vascular events like stroke or ruptured berry aneurysm are more commonly noted. Liver transplantation (LT) is indicated in children with cholestasis progressing to cirrhosis with decompensation. Other indications for LT include intractable pruritus, recurrent fractures, hepatocellular carcinoma and disfiguring xanthomas. Due to an increased risk of renal impairment noted in ALGS, these patients would require optimized renal sparing immunosuppression in the post-transplant period. As the systemic manifestations of ALGS are protean and a wider spectrum is being increasingly elucidated, a multidisciplinary team needs to be involved in managing these patients. Moreover, many basic-science and clinical questions especially with regard to its presentation and management remain unanswered. The aim of this review is to provide updated insights into the management of the multi-system involvement of ALGS.

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