High childhood serum triglyceride concentrations associate with hepatocellular adenoma development in patients with glycogen storage disease type Ia
Martijn P.D. Haring,
Fabian Peeks,
Maaike H. Oosterveer,
Martijn C.G.J. Brouwers,
Carla E.M. Hollak,
Mirian C.H. Janssen,
Janneke G. Langendonk,
Alexander J.M. Rennings,
Margreet A.E.M. Wagenmakers,
Henkjan J. Verkade,
Terry G.J. Derks,
Vincent E. de Meijer
Affiliations
Martijn P.D. Haring
Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
Fabian Peeks
Department of Metabolic Diseases, Beatrix Children’s Hospital, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
Maaike H. Oosterveer
Department of Pediatrics, Center for Liver Digestive and Metabolic Diseases, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
Martijn C.G.J. Brouwers
Department of Internal Medicine, Division of Endocrinology and Metabolic Disease, Maastricht University Medical Center+, Maastricht, the Netherlands
Carla E.M. Hollak
Department of Endocrinology and Metabolism, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands
Mirian C.H. Janssen
Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, the Netherlands
Janneke G. Langendonk
Department of Internal Medicine, Center for Lysosomal and Metabolic Diseases, Erasmus University Medical Center, University Medical Center Rotterdam, Rotterdam, the Netherlands
Alexander J.M. Rennings
Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, the Netherlands
Margreet A.E.M. Wagenmakers
Department of Internal Medicine, Center for Lysosomal and Metabolic Diseases, Erasmus University Medical Center, University Medical Center Rotterdam, Rotterdam, the Netherlands
Henkjan J. Verkade
Pediatric Gastroenterology and Hepatology, Department of Pediatrics, Beatrix Children’s Hospital, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
Terry G.J. Derks
Department of Metabolic Diseases, Beatrix Children’s Hospital, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
Vincent E. de Meijer
Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Corresponding author. Address: University of Groningen and University Medical Center Groningen, Hanzeplein 1, 9700 RB, Groningen, the Netherlands. Tel.: +31 50 361 2896; fax: +31 50 361 4873.
Background & Aims: Glycogen storage disease type Ia (GSDIa) is an inborn error of carbohydrate metabolism caused by pathogenic variants in the glucose-6-phosphatase catalytic subunit 1 (G6PC1) gene and is associated with hepatocellular adenoma (HCA) formation. Data on risk factors for HCA occurrence in GSDIa are scarce. We investigated HCA development in relation to sex, G6PC1 genotype, and serum triglyceride concentration (TG). Methods: An observational study of patients with genetically confirmed GSDIa ≥12 years was performed. Patients were categorised for sex; presence of 2, 1, or 0 predicted severe G6PC1 variant (PSV); and median TG during childhood (5.65 mmol/L was associated with HCA development at younger age, compared with patients with childhood TG 5.65 mmol/L as an independent risk factor for HCA development (hazard ratio [HR] 6.0; 95% CI 1.2–29.8; p = 0.028). Conclusions: In patients with GSDIa, high childhood TG was associated with an increased risk of HCA, and earlier onset of HCA development, independent of sex-associated hypertriglyceridaemia, and G6PC1 genotype. Lay summary: Glycogen storage disease type Ia (GSDIa) is a rare, inherited metabolic disease that can be complicated by liver tumours (hepatocellular adenomas), which in turn may cause bleeding or progress to liver cancer. Risk factors associated with hepatocellular adenoma formation in patients with GSDIa are largely unknown. In our study, we found that high serum triglyceride concentrations during childhood, but not specific genetic variants, were associated with increased risk of hepatocellular adenoma diagnosis later in life.
