Multiomics approach provides insight into altered choline metabolism and liver injury in patients with glycogen storage disease type Ia

Abstract Glycogen storage disease type Ia (GSDIa) is an inherited disorder of carbohydrate metabolism. Patients present with excessive storage of glycogen and fat in the liver and kidneys and are potentially at risk of developing long-term complications. Currently, the mainstay of treatment is highl...

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Main Authors: Francesca Pirozzi, Ramin Amiri, Camilla Luni, Alessandro Rossi, Daniela Melis, Roberta Fedele, Carmen Rosano, Pietro Strisciuglio, Maaike H. Oosterveer, Terry G. J. Derks, Giancarlo Parenti, Marianna Caterino, Margherita Ruoppolo
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Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-06272-7
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author Francesca Pirozzi
Ramin Amiri
Camilla Luni
Alessandro Rossi
Daniela Melis
Roberta Fedele
Carmen Rosano
Pietro Strisciuglio
Maaike H. Oosterveer
Terry G. J. Derks
Giancarlo Parenti
Marianna Caterino
Margherita Ruoppolo
author_facet Francesca Pirozzi
Ramin Amiri
Camilla Luni
Alessandro Rossi
Daniela Melis
Roberta Fedele
Carmen Rosano
Pietro Strisciuglio
Maaike H. Oosterveer
Terry G. J. Derks
Giancarlo Parenti
Marianna Caterino
Margherita Ruoppolo
author_sort Francesca Pirozzi
collection DOAJ
description Abstract Glycogen storage disease type Ia (GSDIa) is an inherited disorder of carbohydrate metabolism. Patients present with excessive storage of glycogen and fat in the liver and kidneys and are potentially at risk of developing long-term complications. Currently, the mainstay of treatment is highly tailored dietary regimens aimed at improving metabolic control. In the present study, to better elucidate the mechanisms potentially involved in the development of long-term complications, a mass spectrometry-based strategy was employed for an in-depth characterization of the serum proteomic and metabolomic profile of n.12 GSDIa patients. The detection of differential abundance of highly liver-specific circulating proteins and choline-related metabolites in patients provides new insights into the extent of liver damage and dysregulation of lipid metabolism in GSDIa. Specifically, the differential abundance of serum aldolase B and its positive correlation with traditional liver function markers supports its role as a potential biomarker for long-term monitoring of GSDIa liver injury.
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spelling doaj-art-042224cd7faa46a2a462f181017e8fac2025-08-20T03:37:30ZengNature PortfolioScientific Reports2045-23222025-07-0115111710.1038/s41598-025-06272-7Multiomics approach provides insight into altered choline metabolism and liver injury in patients with glycogen storage disease type IaFrancesca Pirozzi0Ramin Amiri1Camilla Luni2Alessandro Rossi3Daniela Melis4Roberta Fedele5Carmen Rosano6Pietro Strisciuglio7Maaike H. Oosterveer8Terry G. J. Derks9Giancarlo Parenti10Marianna Caterino11Margherita Ruoppolo12Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico IIDepartment of Civil, Chemical, Environmental and Materials Engineering (DICAM), University of BolognaDepartment of Civil, Chemical, Environmental and Materials Engineering (DICAM), University of BolognaSection of Pediatrics, Department of Translational Medical Sciences, University of Naples Federico IIDepartment of Medicine, Surgery and Dentistry ‘Scuola Medica Salernitana’, University of SalernoCEINGE—Biotecnologie Avanzate Franco Salvatore S.C.A R.L.Section of Pediatrics, Department of Translational Medical Sciences, University of Naples Federico IISection of Pediatrics, Department of Translational Medical Sciences, University of Naples Federico IIDepartment of Pediatrics and Laboratory Medicine, University Medical Center Groningen, University of GroningenSection of Metabolic Diseases, Beatrix Children’s Hospital, University Medical Centre Groningen, University of GroningenSection of Pediatrics, Department of Translational Medical Sciences, University of Naples Federico IIDepartment of Molecular Medicine and Medical Biotechnology, University of Naples Federico IIDepartment of Molecular Medicine and Medical Biotechnology, University of Naples Federico IIAbstract Glycogen storage disease type Ia (GSDIa) is an inherited disorder of carbohydrate metabolism. Patients present with excessive storage of glycogen and fat in the liver and kidneys and are potentially at risk of developing long-term complications. Currently, the mainstay of treatment is highly tailored dietary regimens aimed at improving metabolic control. In the present study, to better elucidate the mechanisms potentially involved in the development of long-term complications, a mass spectrometry-based strategy was employed for an in-depth characterization of the serum proteomic and metabolomic profile of n.12 GSDIa patients. The detection of differential abundance of highly liver-specific circulating proteins and choline-related metabolites in patients provides new insights into the extent of liver damage and dysregulation of lipid metabolism in GSDIa. Specifically, the differential abundance of serum aldolase B and its positive correlation with traditional liver function markers supports its role as a potential biomarker for long-term monitoring of GSDIa liver injury.https://doi.org/10.1038/s41598-025-06272-7Glycogen storage disease type IaMultiomicsLipid metabolismLiver injurySerum biomarkersALDOB
spellingShingle Francesca Pirozzi
Ramin Amiri
Camilla Luni
Alessandro Rossi
Daniela Melis
Roberta Fedele
Carmen Rosano
Pietro Strisciuglio
Maaike H. Oosterveer
Terry G. J. Derks
Giancarlo Parenti
Marianna Caterino
Margherita Ruoppolo
Multiomics approach provides insight into altered choline metabolism and liver injury in patients with glycogen storage disease type Ia
Scientific Reports
Glycogen storage disease type Ia
Multiomics
Lipid metabolism
Liver injury
Serum biomarkers
ALDOB
title Multiomics approach provides insight into altered choline metabolism and liver injury in patients with glycogen storage disease type Ia
title_full Multiomics approach provides insight into altered choline metabolism and liver injury in patients with glycogen storage disease type Ia
title_fullStr Multiomics approach provides insight into altered choline metabolism and liver injury in patients with glycogen storage disease type Ia
title_full_unstemmed Multiomics approach provides insight into altered choline metabolism and liver injury in patients with glycogen storage disease type Ia
title_short Multiomics approach provides insight into altered choline metabolism and liver injury in patients with glycogen storage disease type Ia
title_sort multiomics approach provides insight into altered choline metabolism and liver injury in patients with glycogen storage disease type ia
topic Glycogen storage disease type Ia
Multiomics
Lipid metabolism
Liver injury
Serum biomarkers
ALDOB
url https://doi.org/10.1038/s41598-025-06272-7
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