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Cardiomyopathy as presenting sign of glycogenin-1 deficiency-report of three cases and review of the literature.

Hedberg-Oldfors, C; Glamuzina, E; Ruygrok, P; Anderson, LJ; Elliott, P; Watkinson, O; Occleshaw, C; Abernathy, M; Turner, C; Kingston, N; et al. Hedberg-Oldfors, C; Glamuzina, E; Ruygrok, P; Anderson, LJ; Elliott, P; Watkinson, O; Occleshaw, C; Abernathy, M; Turner, C; Kingston, N; Murphy, E; Oldfors, A (2017) Cardiomyopathy as presenting sign of glycogenin-1 deficiency-report of three cases and review of the literature. J Inherit Metab Dis, 40 (1). pp. 139-149. ISSN 1573-2665 https://doi.org/10.1007/s10545-016-9978-1
SGUL Authors: Anderson, Lisa

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Abstract

We describe a new type of cardiomyopathy caused by a mutation in the glycogenin-1 gene (GYG1). Three unrelated male patients aged 34 to 52 years with cardiomyopathy and abnormal glycogen storage on endomyocardial biopsy were homozygous for the missense mutation p.Asp102His in GYG1. The mutated glycogenin-1 protein was expressed in cardiac tissue but had lost its ability to autoglucosylate as demonstrated by an in vitro assay and western blot analysis. It was therefore unable to form the primer for normal glycogen synthesis. Two of the patients showed similar patterns of heart dilatation, reduced ejection fraction and extensive late gadolinium enhancement on cardiac magnetic resonance imaging. These two patients were severely affected, necessitating cardiac transplantation. The cardiomyocyte storage material was characterized by large inclusions of periodic acid and Schiff positive material that was partly resistant to alpha-amylase treatment consistent with polyglucosan. The storage material had, unlike normal glycogen, a partly fibrillar structure by electron microscopy. None of the patients showed signs or symptoms of muscle weakness but a skeletal muscle biopsy in one case revealed muscle fibres with abnormal glycogen storage. Glycogenin-1 deficiency is known as a rare cause of skeletal muscle glycogen storage disease, usually without cardiomyopathy. We demonstrate that it may also be the cause of severe cardiomyopathy and cardiac failure without skeletal muscle weakness. GYG1 should be included in cardiomyopathy gene panels.

Item Type: Article
Additional Information: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http:// creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
Keywords: Genetics & Heredity, 1103 Clinical Sciences
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) > Cardiac (INCCCA)
Journal or Publication Title: J Inherit Metab Dis
ISSN: 1573-2665
Language: eng
Dates:
DateEvent
January 2017Published
7 October 2016Published Online
12 September 2016Accepted
Publisher License: Creative Commons: Attribution 4.0
PubMed ID: 27718144
Go to PubMed abstract
URI: http://openaccess.sgul.ac.uk/id/eprint/108697
Publisher's version: https://doi.org/10.1007/s10545-016-9978-1

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