OBJECTIVES: Glycogen Storage Disease Type III (GSDIII) is a rare inherited deficiency of glycogen-debranching enzyme characterized by organ dysfunction due to glycogen accumulation in tissues, as well as hypoglycemia. Current management practices to avoid hypoglycemia and preserve skeletal and cardiac muscles include a high-protein diet and uncooked cornstarch supplementation. This retrospective cohort study investigated common and serious complications among US patients with GSDIII.

METHODS: PearlDiver claims database with Mariner dataset was searched for patients diagnosed with GSDIII (ICD-10-D-E7403) and ≥12 months continuous enrollment in insurance between October 2015 and February 2020. A healthy comparator group was generated using propensity-score age- and sex-matching (1:20 ratio). Complications selected through literature review and expert clinical review were identified using ICD-10 diagnosis codes.

RESULTS: Overall, 230 patients with GSDIII and 4,600 comparators were included (female, 50%; mean age, 24.3 years; mean enrollment, 3.5 years). Complications were diagnosed among 96.1% of patients with GSDIII versus 74.8% of comparators. The most frequent complications among patients with GSDIII versus comparators were hepatomegaly (37.4% vs 0.6%), abdominal pain (36.5% vs 23.1%), hyperlipidemia (32.6% vs 16.2%), and nutritional deficiency (32.6% vs 12.3%). Additional serious complications were hypoglycemia (23.5% vs 0.9%), cardiomyopathy (14.3% vs 0.8%), liver cirrhosis (9.1% vs 0.3%), and rhabdomyolysis (6.5% vs <0.2%). Cardiovascular complications were frequent and included arrhythmia (18.7% vs 5.8%), cardiomegaly (17.0% vs 1.8%), heart valve disorder (10.0% vs 2.6%), and heart failure (6.5% vs 2.9%). Common musculoskeletal complications included muscle weakness (12.2% vs 2.8%) and myopathy (7.8% vs <0.2%). Psychiatric complications included anxiety (19.6% vs 15.6%) and depression (16.5% vs 12.5%).

CONCLUSION: GSDIII is associated with high prevalence of complications, including serious cardiovascular, hepatic, and musculoskeletal manifestations. Nutritional and gastrointestinal complications were especially frequent and may be related to dietary management measures. These findings highlight the large unmet medical need for patients with GSDIII.