OBJECTIVES: Glycogen Storage Disease Type Ia (GSDIa) is an inherited disorder caused by deficiency of glucose-6-phosphatase that results in impaired release of glucose from glycogen, putting patients at risk for acute hypoglycemia. Patients also develop hepatomegaly, nephromegaly, and abnormal/delayed growth. Current disease management requires frequent consumption of raw cornstarch on a strict schedule, sometimes throughout the night. This retrospective cohort study investigated comorbidities in adults with GSDIa.

METHODS: PearlDiver claims database with Mariner dataset was searched for patients aged ≥18 years with GSDI (ICD-10-D-E7401), no diagnoses related to inflammatory bowel disease (indicative of GSDIb), and ≥12 months continuous enrollment in insurance between October 2015 and Dec 2019. GSDIa-related comorbidities were identified via ICD-10 diagnosis codes. Related codes were grouped and accuracy was confirmed by clinical experts.

RESULTS: 1,418 patients were included (male, 54.5%), mean age 46.0 years (standard deviation [SD] 17.1) with mean insurance enrollment duration of 3.26 years. Most prevalent (≥40%) comorbidities included hypertension (57.9%), anemia (52.3%), nutritional deficiency (47.7%), hyperlipidemia (43.1%), and abdominal pain (42.4%). Noteworthy comorbidities included depression (28.6%), chronic kidney disease (CKD, 22.5%), atherosclerotic heart disease (AHD, 15.4%), and hepatocellular carcinoma (HCC, 1.1%). Additionally, 2.3% underwent liver and/or kidney transplant.

CONCLUSIONS: GSDIa in adults is commonly associated with numerous interrelated comorbidities that may be serious. Rates of HCC were notable, possibly due to progressive buildup of glycogen in organ tissues causing liver inflammation and hepatic adenomas. Over one half of the population experienced hypertension or anemia, likely related to high rates of CKD. Other frequent comorbidities included nutritional deficiency, anemia, abdominal pain, and obesity–possibly attributed to large consumption of cornstarch, which is not nutrient rich. Depression was common and may result from the seriousness of disease symptoms and demanding management strategy. This analysis reveals that GSDIa is associated with many comorbidities and large unmet need.