Pancreatic involvement in EPG5-related disorders

Famili, Dennis T, Elghazali, Gehad, Argili, Emanuela, Saneto, Russell P, Harris, Michael, Gerasimenko, Oleg ORCID: https://orcid.org/0000-0003-2573-8258, Gerasimenko, Julia ORCID: https://orcid.org/0000-0002-2262-2543, Fanto, Manolis, Dafsari, Hormos Salimi and Jungbluth, Heinz 2025. Pancreatic involvement in EPG5-related disorders. Molecular Genetics and Metabolism Reports 45 , 101273. 10.1016/j.ymgmr.2025.101273

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Abstract

Vici syndrome is a severe neurodevelopmental multisystem disorder characterized by callosal agenesis, cataracts, cardiomyopathy, combined immunodeficiency and hypopigmentation. There may be additional variable involvement of other organs. VS is caused by recessive mutations in EPG5, encoding a tethering factor with important roles in autophagy, an essential cellular homeostatic mechanism involved in metabolic adaptation, infection defence and quality control of proteins and organelles. Acute pancreatitis is an inflammatory syndrome caused by an acute injury resulting in failure of safeguarding mechanisms preventing autodigestion. Chronic pancreatitis is characterized by replacement of pancreatic parenchyma with fibrotic tissue following repeated injury, resulting in endocrine and exocrine insufficiency. In addition to common causes such as excessive ethanol consumption, gallstones and pharmacological factors, there are likely to be additional genetic contributors. Here we report 3 patients with EPG5-related Vici syndrome and not previously recognized pancreatic involvement, ranging from otherwise asymptomatic amylase elevations to acute pancreatitis and pancreatic insufficiency. A topical literature review on the role of autophagy and autophagy-related genes in the pancreas suggested that autophagy defects may affect critical pathological events involved in pancreatitis, in particular abnormal vacuole formation in acinar cells, inappropriate intra-acinar trypsinogen activation, mitochondrial dysfunction and disturbed calcium homeostasis. These findings illustrate the importance of EPG5 and other autophagy-related genes in normal pancreatic function and expand the phenotypical spectrum of EPG5-related disorders.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Biosciences
Additional Information:	License information from Publisher: LICENSE 1: Title: cc by, Type: cc by
Publisher:	Elsevier
Date of First Compliant Deposit:	10 December 2025
Date of Acceptance:	4 November 2025
Last Modified:	10 Dec 2025 09:30
URI:	https://orca.cardiff.ac.uk/id/eprint/183077

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