RBCK1-related disease: A rare multisystem disorder with polyglucosan storage, auto-inflammation, recurrent infections, skeletal, and cardiac myopathy-Four additional patients and a review of the current literature

Rahul Phadke; Carola Hedberg-Oldfors; Renata S Scalco; David M Lowe; Michael Ashworth; Marco Novelli; Roshni Vara; Aine Merwick; Halima Amer; Reecha Sofat; Max Sugarman; Ana Jovanovic; Mark Roberts; Vasiliki Nakou; Andrew King; Istvan Bodi; Heinz Jungbluth; Anders Oldfors; Elaine Murphy

doi:10.1002/jimd.12234

RBCK1-related disease: A rare multisystem disorder with polyglucosan storage, auto-inflammation, recurrent infections, skeletal, and cardiac myopathy-Four additional patients and a review of the current literature

J Inherit Metab Dis. 2020 Sep;43(5):1002-1013. doi: 10.1002/jimd.12234. Epub 2020 Apr 16.

Authors

Rahul Phadke^{1

2

3}, Carola Hedberg-Oldfors⁴, Renata S Scalco^{2

5}, David M Lowe⁶, Michael Ashworth⁷, Marco Novelli⁸, Roshni Vara⁹, Aine Merwick¹⁰, Halima Amer¹¹, Reecha Sofat¹¹, Max Sugarman¹², Ana Jovanovic¹², Mark Roberts¹³, Vasiliki Nakou¹⁴, Andrew King¹⁵, Istvan Bodi¹⁵, Heinz Jungbluth^{14

16

17}, Anders Oldfors⁴, Elaine Murphy¹⁸

Affiliations

¹ Dubowitz Neuromuscular Centre, UCL Institute of Child Health, Great Ormond Street Hospital, London, UK.
² MRC Centre for Neuromuscular Diseases, University College London, Queen Square, London, UK.
³ Division of Neuropathology, National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
⁴ Department of Pathology and Genetics, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
⁵ CAPES Foundation, Ministry of Education of Brazil, Brasilia DF, Brazil.
⁶ Department of Immunology, Royal Free Hospital, London, UK and Institute of Immunity and Transplantation, University College London, Royal Free Campus, London, UK.
⁷ Department of Histopathology, Great Ormond Street Hospital, London, UK.
⁸ Department of Histopathology, University College London NHS Foundation Trust, London, UK.
⁹ Department of Paediatric Inherited Metabolic Disease, Evelina London Children's Hospital, London, UK.
¹⁰ Department of Neurology, Beaumont Hospital, Dublin, Ireland.
¹¹ Department of Clinical Pharmacology, University College London NHS Foundation Trust, London, UK.
¹² Mark Holland Metabolic Unit, Salford Royal NHS Foundation Trust, Salford, UK.
¹³ Great Manchester Neurosciences Unit, Salford Royal NHS Foundation Trust, Salford, UK.
¹⁴ Department of Paediatric Neurology, Neuromuscular Service, Evelina London Children's Hospital, Guy's and St. Thomas' Hospital NHS Foundation Trust, London, UK.
¹⁵ Department of Clinical Neuropathology, King's College Hospital, London, UK.
¹⁶ Randall Division for Cell and Molecular Biophysics, Muscle Signaling Section, King's College London, London, UK.
¹⁷ Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
¹⁸ Charles Dent Metabolic Unit, National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.

PMID: 32187699
DOI: 10.1002/jimd.12234

Abstract

In this article, we report four new patients, from three kindreds, with pathogenic variants in RBCK1 and a multisystem disorder characterised by widespread polyglucosan storage. We describe the clinical presentation of progressive skeletal and cardiac myopathy, combined immunodeficiencies and auto-inflammation, illustrate in detail the histopathological findings in multiple tissue types, and report muscle MRI findings.

Keywords: RBCK1; auto-inflammation; cardio; glycogen; myopathy; polyglucosan.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Child
Child, Preschool
Female
Glucans / metabolism*
Glycogen Storage Disease / genetics*
Glycogen Storage Disease / metabolism*
Humans
Inflammation / pathology
Male
Muscle, Skeletal / pathology
Muscular Diseases / pathology
Reinfection / pathology
Transcription Factors / genetics*
Ubiquitin-Protein Ligases / genetics*

Substances

Glucans
Transcription Factors
polyglucosan
RBCK1 protein, human
Ubiquitin-Protein Ligases

Grants and funding

DH_/Department of Health/United Kingdom