Evaluation of FGF21 levels in patients diagnosed with glycogen storage diseases with liver involvement

Introduction: Glycogen storage diseases (GSDs) are inherited metabolic diseases caused by enzyme deficiencies that affect the glycogen synthesis and breakdown. While some of these diseases are inherited in X-linked manner, most of them are inherited autosomal recessive and can affect organs such as the liver, muscle and heart. GSD subtypes with liver involvement often present with symptoms such as fasting hypoglycemia and hepatomegaly, with medical nutrition therapy being the cornerstone of treatment. Fibroblast Growth Factor-21 (FGF21) is a crucial peptide hormone involved in the regulation of lipid, glucose, and energy metabolism. Although FGF21 can be released from various organs and tissues, it is predominantly produced by the liver. FGF21 release may increase in the liver during fasting, in the pancreas during overnutrition, in the muscle during exercise, and in the brown adipose tissue after exposure to cold. This hormone has beneficial effects on metabolic health, including increased glucose uptake, promotion of thermogenesis and energy expenditure, and enhanced insulin sensitivity. Purpose: This study aimed to determine the levels of FGF21 in GSD patients with liver involvement, followed by Çukurova University Faculty of Medicine, Department of Pediatric Metabolism and Nutrition, to assess differences according to GSD types, and to evaluate the relationship of FGF21 levels with biochemical parameters. Materials and Methods: Our study included 50 (26F/24M) glycogen storage patients with liver involvement who presented to Çukurova University Faculty of Medicine, Pediatric Metabolism and Nutrition Outpatient Clinic between July 2022 and May 2023. Of these patients, 10 (20%) had GSD type Ia, 2 (4%) had GSD type Ib, 16 (32%) had GSD type III, 3 (6%) had GSD type VI, 8 (16%) had GSD type IXa, 4 (8%) had GSD type IXb, and 7 (14%) had GSD type IXc. Serum FGF21 levels were measured. The association between GSD subtypes, biochemical examinations, abdominal ultrasonographic imaging findings, growth parameters (weight standard deviation score [SDS], height SDS, body mass index SDS) and FGF21 were evaluated. Results: 52% of the patients were female and 48% were male. The mean age at admission was 142.26±76.19 (23-360) months. The rate of consanguineous marriage was 72% and the rate of positive family history was 54%. The most common reasons for admission were abdominal distension, hepatomegaly, hypoglycemia, selective family screening and growth retardation. The mean age of the patients at diagnosis was 34.40±39.14 (0-188) months, with all patients were diagnosed before 18 years of age. At diagnosis, 80% had a normal body weight for age and 58% had normal height. The median FGF21 value for healthy individuals is expected to be between 100-200 pg/ml. In our study, the average FGF21 level of the patients was 318.3±126.9 (min-max: 148.52-647.44) pq/ml. The highest FGF21 levels were observed in patients with GSD type IXc (464.31±112.88 pq/ml), followed by type IXa (343.35 ± 137.18 pg/ml) and type III (323.80 ± 116.04 pg/ml). FGF21 levels in other types were below the overall group average. FGF21 levels in type IXc patients were statistically significantly higher than other types (p = 0.001). A positive correlation was found between FGF21 levels and lactate dehydrogenase and gamma-glutamyl transferase levels. Conclusion: There are no other studies in the literature evaluating serum FGF21 levels in GDH patients. In our study, the mean FGF21 levels in patients were found to be similar to those in patients with acute fatty liver and hepatosteatosis reported in the literature. When all subtypesglycogen storage diseases were evaluated together, no significant differences in FGF21 levels were observed between the subtypes. However, when comparing type IXc, which has been reported as a more severe phenotype causing progressive liver cirrhosis, with other types, FGF21 levels were found to be statistically significantly higher. This suggests that FGF21 could potentially be used as a biomarker for identifying patients with severe phenotypes. Key words: Glycogen storage disease, liver involvement, Fibroblast Growth Factor-21,