Glycogen storage diseases: An update

Abstract

Glycogen storage diseases (GSDs), also referred to as glycogenoses, are inherited metabolic disorders of glycogen metabolism caused by deficiency of enzymes or transporters involved in the synthesis or degradation of glycogen leading to aberrant storage and/or utilization. The overall estimated GSD incidence is 1 case per 20000-43000 live births. There are over 20 types of GSD including the subtypes. This heterogeneous group of rare diseases represents inborn errors of carbohydrate metabolism and are classified based on the deficient enzyme and affected tissues. GSDs primarily affect liver or muscle or both as glycogen is particularly abundant in these tissues. However, besides liver and skeletal muscle, depending on the affected enzyme and its expression in various tissues, multiorgan involvement including heart, kidney and/or brain may be seen. Although GSDs share similar clinical features to some extent, there is a wide spectrum of clinical phenotypes. Currently, the goal of treatment is to maintain glucose homeostasis by dietary management and the use of uncooked cornstarch. In addition to nutritional interventions, pharmacological treatment, physical and supportive therapies, enzyme replacement therapy (ERT) and organ transplantation are other treatment approaches for both disease manifestations and long-term complications. The lack of a specific therapy for GSDs has prompted efforts to develop new treatment strategies like gene therapy. Since early diagnosis and aggressive treatment are related to better prognosis, physicians should be aware of these conditions and include GSDs in the differential diagnosis of patients with relevant manifestations including fasting hypoglycemia, hepatomegaly, hypertransaminasemia, hyperlipidemia, exercise intolerance, muscle cramps/pain, rhabdomyolysis, and muscle weakness. Here, we aim to provide a comprehensive review of GSDs. This review provides general characteristics of all types of GSDs with a focus on those with liver involvement.

Glycogen Storage Disease: Expert Opinion on Clinical Diagnosis Revisited after Molecular Testing

“…GSDs comprise a group of inborn errors of metabolism (IEM) due to dysfunctions in glycogen metabolism causing multisystemic diseases that can present at any age from the neonatal period to adulthood [1][2][3][4][5][6]. The characteristics of GSDs depend on the abnormal site of glycogen metabolism.…”

“…Recent reviews suggest 20 types and subtypes of GSDs, divided into hepatic, muscular, mixed (hepatomuscular), and others limited to specific systems (two cardiac forms and one cerebral). The estimated GSD incidence is 1 case per 20,000-43,000 live births, and 80% of hepatic GSDs are caused by types I, III, and IX [4,7,8]. A summary of those with liver involvement is presented in Table 1.…”

“…Table 1. Genetic and epidemiologic characteristics of the hepatic GSDs [4,5,8]. The first step in the diagnosis of GSDs is a characterization of the patient's phenotype and clinical features [5].…”

“…The first step in the diagnosis of GSDs is a characterization of the patient's phenotype and clinical features [5]. Although GSDs share similar clinical features to some extent, there is a wide spectrum of the phenotypic disease continuum [4,5]. The resulting phenotypic classes for each type of GSD can be used to aid diagnosis and treatment.…”

“…Some metabolites inform the differential diagnosis of GSDs and can be useful for disease surveillance, including the measures of glucose, ketones, blood lactate, serum lipids and triglycerides, liver transaminases, uric acid, creatine kinase, and neutrophils count [5]. Hypoglycemia is the hallmark of hepatic GSDs, and hepatomegaly is a cardinal manifestation of GSDs with liver involvement, except for GSD 0 [4].…”