Glycogen storage disease type I: Genetic etiology, clinical manifestations, and conventional and gene therapies

Abstract

Glycogen storage disease type I (GSDI) is an inherited metabolic disorder characterized by a deficiency of enzymes or proteins involved in glycogenolysis and gluconeogenesis, resulting in excessive intracellular glycogen accumulation. While GSDI is classified into four different subtypes based on molecular genetic variants, GSDIa accounts for approximately 80%. GSDIa and GSDIb are autosomal recessive disorders caused by deficiencies in glucose‐6‐phosphatase (G6Pase‐α) and glucose‐6‐phosphate‐transporter (G6PT), respectively. For the past 50 years, the care of patients with GSDI has been improved following elaborate dietary managements. GSDI patients currently receive dietary therapies that enable patients to improve hypoglycemia and alleviate early symptomatic signs of the disease. However, dietary therapies have many limitations with a risk of calcium, vitamin D, and iron deficiency and cannot prevent long‐term complications, such as progressive liver and renal failure. With the deepening understanding of the pathogenesis of GSDI and the development of gene therapy technology, there is great progress in the treatment of GSDI. Here, we review the underlying molecular genetics and the current clinical management strategies of GSDI patients with an emphasis on promising experimental gene therapies.

Pediatrics in the era of precision medicine and precision epidemiology

“…But if the factors that have the highest impact on the risk and consequences of a possible SARS‐CoV‐2 infection can be identified, protection strategies can be tailored for the different individual situations—aiming at finding a balance between providing the maximal protection to the mother and child from COVID‐19‐related sequelae and the possibility of the other to live a life free of unnecessary restrictions in the very sensitive life situation. As another example, Zhong and colleagues provide a thorough review of possible treatment opportunities for glycogen storage disease type I—a rare disorder that has previously been managed primarily by nutritional interventions 5 . While rare diseases have been to some extent neglected in the past due to resource limitations and lack of high‐quality evidence, this new knowledge opens new opportunities.…”