Abstract
Glycogen storage disease type IV (GSD IV) is an ultra-rare autosomal recessive disorder caused by pathogenic variants in GBE1 which results in reduced or deficient glycogen branching enzyme activity. Consequently, glycogen synthesis is impaired and leads to accumulation of poorly branched glycogen known as polyglucosan. GSD IV is characterized by a remarkable degree of phenotypic heterogeneity with presentations in utero, during infancy, early childhood, adolescence, or middle to late adulthood. The clinical continuum encompasses hepatic, cardiac, muscular, and neurologic manifestations that range in severity. The adult-onset form of GSD IV, referred to as adult polyglucosan body disease (APBD), is a neurodegenerative disease characterized by neurogenic bladder, spastic paraparesis, and peripheral neuropathy. There are currently no consensus guidelines for the diagnosis and management of these patients, resulting in high rates of misdiagnosis, delayed diagnosis, and lack of standardized clinical care. To address this, a group of experts from the United States developed a set of recommendations for the diagnosis and management of all clinical phenotypes of GSD IV, including APBD, to support clinicians and caregivers who provide long-term care for individuals with GSD IV. The educational resource includes practical steps to confirm a GSD IV diagnosis and best practices for medical management, including (a) imaging of the liver, heart, skeletal muscle, brain, and spine, (b) functional and neuromusculoskeletal assessments, (c) laboratory investigations, (d) liver and heart transplantation, and (e) long-term follow-up care. Remaining knowledge gaps are detailed to emphasize areas for improvement and future research.
Original language | English (US) |
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Article number | 107525 |
Journal | Molecular Genetics and Metabolism |
Volume | 138 |
Issue number | 3 |
DOIs | |
State | Published - Mar 2023 |
Bibliographical note
Funding Information:The authors gratefully acknowledge the patients and caregivers who have served as “patient advocates” and provided input for the development of this resource, as well as the Association for Glycogen Storage Disease and the Adult Polyglucosan Body Disease Research Foundation for their critical review and suggestions. The authors also acknowledge Dr. Ghada Hijazi, Leticia Flores, and Jenna Foltz for their assistance with the creation of this resource, and Erica Nading and Dr. Jordan Foreman for their review. Figs. 1 and 2 were created with BioRender.com.
Funding Information:
AA, SLA, DSB, TAB, LEC, MH, PBK, BTK, RLK, PSK, APL, JLO-M, SP, ALS, CS-A, and RS have no relevant disclosures. HOA has received research funding from The Keith B. Hayes Foundation for investigating polyglucosan diseases. DSG serves on the Executive Board of the APBD Research Foundation. Funding of this resource was provided in part by the Association for Glycogen Storage Disease that was restricted to the use of developing this clinical practice resource.
Publisher Copyright:
© 2023
Keywords
- Adult polyglucosan body disease
- Andersen disease
- Clinical practice guideline
- Diagnosis guideline
- Glycogen branching enzyme
- Glycogen storage disease type IV
- Management guideline
PubMed: MeSH publication types
- Journal Article
- Review