Bempedoic Acid Treatment in Four Adult Patients with Glycogen Storage Disease Type 1a: A Retrospective, Exploratory Case Series

Background: Glycogen storage disease type 1a (GSD 1a) is an inborn error of metabolism due to glucose-6-phosphatase deficiency. Treatment consists of frequent, carbohydrate-rich meals, intake of glucose polymers like uncooked cornstarch, or drip feeding in small infants. Although dietary treatment is challenging, it has improved the long-term outcomes for patients with GSD 1a. Nevertheless, several complications, including dyslipidaemia, remain difficult to manage, and early atherosclerosis with risk for ischemic stroke is a potential long-term concern. We propose bempedoic acid (BA) as a potential treatment option for dyslipidaemia in adult patients with GSD 1a. BA is an approved lipid-lowering therapy and may have additional beneficial metabolic effects in patients with GSD 1a. We hypothesize that BA may reduce malonyl-CoA concentrations and thereby alleviate the inhibition of mitochondrial fatty acid oxidation. This could potentially contribute to improved metabolic stability in patients with GSD 1a. Methods: Four adult female patients with GSD 1a and dyslipidaemia received BA at a dose of 180 mg once daily for 2–5 years. In this retrospective case series, we explored potential additional effects of BA treatment beyond its established lipid-lowering effect. Results: Under BA treatment, patients reported prolonged fasting periods, and carbohydrate intake could be reduced in some patients. Plasma lactate concentrations decreased during treatment, while triglyceride concentrations decreased in two patients but increased in the others. Two patients experienced a slight, clinically irrelevant increase in serum uric acid concentrations, a known adverse effect of BA. No other adverse effects were observed. Conclusions: In this retrospective, uncontrolled, single-center case series, BA was associated not only with its expected lipid-lowering effect, but also with potential improvements in metabolic control and prolonged fasting tolerance in adults with GSD 1a. However, these preliminary observations require confirmation in larger, prospective, controlled studies. Future studies should include standardized metabolic assessments and direct measurements of key metabolites involved in the pathophysiology of GSD 1a. Preclinical studies using appropriate animal models may further contribute to elucidating the underlying mechanisms and potential metabolic effects of BA.