Glycogen storage disease type III: a mixed-methods study to assess the burden of disease.

Background: Glycogen storage disease type III (GSD III) is a rare inherited disorder that results from a glycogen debranching enzyme deficiency. Objectives: The purpose of this research was to collect data on the signs, symptoms, and impacts of GSD III from the perspective of adult patients and caregivers of individuals with GSD III. Design: Online survey and qualitative interviews. Methods: Following institutional review board approval, adult patients and caregivers of children with GSD III were recruited through advocacy networks and clinical sites. If eligible, participants were consented, screened, and sent a survey and/or participated in a 60-min interview. The survey and interview included questions about family history, diagnosis, signs and symptoms, impacts, and management of GSD III. Conceptual models were developed following the analysis of results. Results: In all, 29 adults and 46 caregivers completed the online survey and/or the interviews with 73 survey and 19 interview respondents. Adults and caregivers reported digestive, musculoskeletal, growth and physical appearance, and cardiac signs and symptoms. Liver conditions were reported by most respondents (83%). Adults and caregivers frequently reported impacts such as difficulty keeping up with peers (77%) and difficulty exercising/difficulty with physical activity (53%). Hypoglycemia was frequently reported in both adults and children, with more than half reporting hospitalizations due to hypoglycemia. Caregivers focused on hypoglycemia when reporting signs/symptoms that most interfere with their child's life and prevention of hypoglycemia as a desired outcome for an effective therapy. Adults most often reported muscle weakness as a top interfering symptom and the most important goal of a potential therapy. Impacts were also reported in activities of daily living, cognitive, emotional, work/school, and sleep domains. Conclusion: Individuals with GSD III experience a broad spectrum of symptoms and disease impacts. There is an unmet need for therapies that improve metabolic control, reduce the burden of dietary management, reduce fatigue and liver problems, and improve muscle strength and function.