The Clinical Burden and Complications Associated With Glycogen Storage Disease Type Ia (GSDIa): Results From a Systematic Literature Review
Author(s)
Manpreet K. Sidhu, BA, MBA, PhD1, Dagmara Chojecki, MSc2, Nicole Tunstall, BSc, MSc3, Louise Perrault, MSc2, Hema Viswanathan, PhD4, Elizabeth Dorn, PhD4, Richard Collis, MD4, Kadakkal Radhakrishnan, MD5, David F Rodriguez-Buritica, MD6.
1Executive Director, Global HEOR and Epidemiology, Ultragenyx Pharmaceutical Inc., Novato, CA, USA, 2International Market Access Consulting, Montreal, QC, Canada, 3International Market Access Consulting GmbH, Zug, Switzerland, 4Ultragenyx Pharmaceutical Inc., Novato, CA, USA, 5Cleveland Clinic, Cleveland, OH, USA, 6Department of Pediatrics, Division of Medical Genetics, McGovern Medical School at the University of Texas Health Science Center at Houston (UTHealth Houston) and Children’s Memorial Hermann Hospital, Houston, TX, USA.
1Executive Director, Global HEOR and Epidemiology, Ultragenyx Pharmaceutical Inc., Novato, CA, USA, 2International Market Access Consulting, Montreal, QC, Canada, 3International Market Access Consulting GmbH, Zug, Switzerland, 4Ultragenyx Pharmaceutical Inc., Novato, CA, USA, 5Cleveland Clinic, Cleveland, OH, USA, 6Department of Pediatrics, Division of Medical Genetics, McGovern Medical School at the University of Texas Health Science Center at Houston (UTHealth Houston) and Children’s Memorial Hermann Hospital, Houston, TX, USA.
OBJECTIVES: Glycogen storage disease type Ia (GSDIa) is a rare metabolic disorder caused by biallelic pathogenic G6PC gene variants, resulting in deficiency of glucose-6-phosphatase, an enzyme essential for the release of glucose from glycogen and the generation of glucose de novo from gluconeogenesis. There are no disease-modifying treatments approved for GSDIa. Patients present with a range of chronic complications and acute complications that include potentially life-threatening episodes of hypoglycemia and metabolic control abnormalities. Current treatment strategies focus on nutritional management, including prescribed cornstarch and dietary restrictions. Due to the low prevalence of the disease, large studies characterizing GSDIa are limited.
METHODS: A comprehensive systematic literature review of epidemiology, clinical burden, treatment strategies, and the humanistic/societal impact of GSDIa was conducted using relevant databases (PubMed, Embase, Cochrane Library-Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews) and grey literature sources. Studies published in English or French after 1970 were included. The review was modeled on the domains of the European Network for Health Technology Assessment (EUnetHTA) Core Model.
RESULTS: A total of 2336 citations were screened, and 329 full-text articles were retrieved for further evaluation. After applying the Population, Intervention, Comparators, Outcomes, Study design (PICOS) criteria,152 publications were eligible for inclusion. A total of 57 publications based on retrospective chart reviews, observational cohort studies, case-control studies, and biochemical analyses investigated comorbidities and complications. GSDIa was found to be associated with acute complications, including abnormalities of glycemic and metabolic control, and chronic complications including, hepatic adenomas, hepatocellular carcinoma, liver transplantation, renal dysfunction, renal transplantation, growth and pubertal impairment, osteoporosis, bleeding tendencies, and endocrine abnormalities.
CONCLUSIONS: GSDIa is associated with various acute and long-term complications, including glycemic, metabolic, hepatic, renal, and other complications, all of which place a substantial burden on patients and caregivers.
METHODS: A comprehensive systematic literature review of epidemiology, clinical burden, treatment strategies, and the humanistic/societal impact of GSDIa was conducted using relevant databases (PubMed, Embase, Cochrane Library-Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews) and grey literature sources. Studies published in English or French after 1970 were included. The review was modeled on the domains of the European Network for Health Technology Assessment (EUnetHTA) Core Model.
RESULTS: A total of 2336 citations were screened, and 329 full-text articles were retrieved for further evaluation. After applying the Population, Intervention, Comparators, Outcomes, Study design (PICOS) criteria,152 publications were eligible for inclusion. A total of 57 publications based on retrospective chart reviews, observational cohort studies, case-control studies, and biochemical analyses investigated comorbidities and complications. GSDIa was found to be associated with acute complications, including abnormalities of glycemic and metabolic control, and chronic complications including, hepatic adenomas, hepatocellular carcinoma, liver transplantation, renal dysfunction, renal transplantation, growth and pubertal impairment, osteoporosis, bleeding tendencies, and endocrine abnormalities.
CONCLUSIONS: GSDIa is associated with various acute and long-term complications, including glycemic, metabolic, hepatic, renal, and other complications, all of which place a substantial burden on patients and caregivers.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
CO236
Topic
Clinical Outcomes, Epidemiology & Public Health, Health Technology Assessment
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
Diabetes/Endocrine/Metabolic Disorders (including obesity), Rare & Orphan Diseases