title: Energy balance, glucose and lipid metabolism, cardiovascular risk and liver disease burden in adult patients with type 1 Gaucher disease.
abstract: Gaucher disease (GD), the most prevalent lysosomal storage disease, is characterized by systemic accumulation of macrophages engorged with glycosphingolipid-laden lysosomes. Even though both lysosomes and sphingolipids play a pivotal role in metabolic homeostasis, little is known on metabolic abnormalities associated with GD. In this review, we discuss the peculiarity of energy balance and glucose and lipid metabolism in adult type 1 GD patients. Moreover, we evaluate the potential relationship between these metabolic derangements, cardiovascular risk and chronic liver disease. The limited data available show that adult type 1 GD is characterized by a hypermetabolic state, peripheral insulin resistance and hypolipidemia with markedly reduced HDL-cholesterol levels, partially reverted by enzyme replacement therapy (ERT) or substrate reduction therapy (SRT). Although this unfavorable metabolic profile has not been associated with increased incidence of type 2 diabetes and premature atherosclerosis, a natural history study has shown that cardio-cerebrovascular events and malignancy are the leading causes of death in treated type 1 GD patients. Hepatomegaly is frequently observed in GD and ERT/SRT are highly effective in reducing liver volume. Nevertheless, patients with GD may be at increased risk of long-term liver complications including cirrhosis and hepatocellular carcinoma. The role that ERT/SRT and/or lifestyle habits may have on such metabolic features of GD patients, and subsequently on long-term prognosis, deserves further investigations. To gain more insights into the peculiarity of GD metabolism may serve both surveillance and treatment purposes by helping to identify new markers of disease severity and define an updated natural history of GD.
authors.affiliation: Regional Referral Centre for Lysosomal Storage Diseases, Division of Internal Medicine and Metabolism, NOCSAE, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia and AUSL Modena, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Nascimbeni
authors.affiliation: Regional Referral Centre for Lysosomal Storage Diseases, Division of Internal Medicine and Metabolism, NOCSAE, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia and AUSL Modena, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Dalla Salda
authors.affiliation: Regional Referral Centre for Lysosomal Storage Diseases, Division of Internal Medicine and Metabolism, NOCSAE, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia and AUSL Modena, Italy. Electronic address: carubbi@unimore.it.
authors.forename: Francesca
authors.initials: F
authors.lastname: Carubbi
mesh_terms: D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000378:metabolism; D004734:Energy Metabolism; D005776:Gaucher Disease / Q000150:complications* / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007333:Insulin Resistance; D050356:Lipid Metabolism; D008107:Liver Diseases / Q000150:complications* / Q000378:metabolism; D008113:Liver Neoplasms / Q000150:complications / Q000378:metabolism; D024821:Metabolic Syndrome / Q000150:complications / Q000378:metabolism; D012307:Risk Factors
chemical_list: D005947:Glucose
keywords: Gaucher disease; Glucocerebrosidase deficiency; Hepatocellular carcinoma; High-density lipoprotein cholesterol; Insulin resistance; Lysosomal storage disease; Resting energy expenditure