Pancreatitis in RYR1-related disorders

Famili, Dennis T., Mistry, Arti, Gerasimenko, Oleg ORCID: https://orcid.org/0000-0003-2573-8258, Gerasimenko, Julia ORCID: https://orcid.org/0000-0002-2262-2543, Tribe, Rachel M., Kyrana, Eirini, Dhawan, Anil, Goldberg, Michael F., Voermans, Nicol, Willis, Tracey and Jungbluth, Heinz 2023. Pancreatitis in RYR1-related disorders. Neuromuscular Disorders 33 (10) , pp. 769-775. 10.1016/j.nmd.2023.09.003

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Abstract

Mutations in RYR1 encoding the ryanodine receptor (RyR) skeletal muscle isoform (RyR1) are a common cause of inherited neuromuscular disorders. Despite its expression in a wide range of tissues, non-skeletal muscle manifestations associated with RYR1 mutations have only been rarely reported. Here, we report three patients with a diagnosis of Central Core Disease (CCD), King-Denborough Syndrome (KDS) and Malignant Hyperthermia Susceptibility (MHS), respectively, who in addition to their (putative) RYR1-related disorder also developed symptoms and signs of acute pancreatitis. In two patients, episodes were recurrent, with severe multisystem involvement and sequelae. RyR1-mediated calcium signalling plays an important role in normal pancreatic function but has also been critically implicated in the pathophysiology of acute pancreatitis, particularly in bile acid- and ethanol-induced forms. Findings from relevant animal models indicate that pancreatic damage in these conditions may be ameliorated through administration of the specific RyR1 antagonist dantrolene and other compounds modifying pancreatic metabolism including calcium signalling. These observations suggest that patients with RYR1 gain-of-function variants may be at increased risk of developing acute pancreatitis, a condition which should therefore be considered in the health surveillance of such individuals.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
Additional Information:	License information from Publisher: LICENSE 1: URL: http://creativecommons.org/licenses/by-nc/4.0/, Start Date: 2023-09-18
Publisher:	Elsevier
ISSN:	0960-8966
Date of First Compliant Deposit:	19 September 2023
Date of Acceptance:	15 September 2023
Last Modified:	28 Nov 2023 15:49
URI:	https://orca.cardiff.ac.uk/id/eprint/162607

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