Abstract
Glycogen storage disease type Ia (GSDIa) is a rare inherited disorder of carbohydrate metabolism due to a deficiency of the glucose-6-phosphatase-alpha (G6Pase-α, G6PC1 gene) involved in both glycogenolysis and gluconeogenesis. Patients show fasting hypoglycaemia, elevated lactate, metabolic acidosis, hypercholesterolemia, hypertriglyceridemia, and hyperuricemia. The accumulation of glycogen and fat in kidneys and liver results in renal disease and hepatomegaly. The clinical outcome of GSDIa patients is often associated with long-term complications, which need therapy adjustments and are therefore challenging. With time, liver adenomas or nephropathy often develop even in patients with apparently stable metabolic control. In addition, a long-term concern is the higher risk of developing metabolic syndrome including insulin-resistance (IR). A better understanding of the pathophysiology of GSDIa is warranted to develop reliable tools to monitor and possibly anticipate long-term complications and treatment response. The availability of a set of biomarkers, detectable in body fluids, can potentially provide critical information on patient conditions by using non-invasive procedures. In this respect, whole blood is an easily accessible and minimally invasive tissue which, reflecting the systemic changes in the body, may provide significant clinical and pathological information on diverse biological processes. A preliminary mass spectrometry-based lipidomic and proteomic study was performed in our laboratories on the serum of a small cohort of patients and controls. GSDIa patients showed a higher total content of ceramides and hexosylceramides compared to controls. Differential proteomic analysis demonstrated the alteration of several cellular pathways including cholesterol metabolism and immune response, suggesting metabolic and inflammatory unbalances in GSDIa patients when compared to controls. The present study is expected to enroll a cohort of 30 GSDIa patients, (equally distributed between males and females), 30 age- and gender-matched healthy controls (HC) and 30 subjects with hyperlipidemia (HS). By increasing the cohort of subjects, we could divide patients in two classes: children (< 16 years old) and adult (> 16 years old). The aims of the project are: 1) generate and integrate profiling independent datasets on GSDIa patients; 2) define molecular pathways that are dysregulated in GSDIa. The data resulting from each independent analysis will be integrated to identify class-specific biomarkers and combination of biomarkers. The multiomic datasets will be finally analysed to evaluate their ability to discriminate patients, as for disease progression and treatment response. Integration will be performed at the statistical, biochemical, and functional level, and will serve as the basis for hypothesis-driven studies on the role of specific pathways in the genesis and progression of the disease.
Project details
Unibo Team Leader: Camilla Luni
Unibo involved Department/s:
Dipartimento di Ingegneria Civile, Chimica, Ambientale e dei Materiali
Coordinator:
Università degli Studi di NAPOLI Federico II(Italy)
Total Unibo Contribution: Euro (EUR) 62.000,00
Project Duration in months: 24
Start Date:
05/10/2023
End Date:
28/02/2026
