title: Neutral lipid storage disease: genetic disorders caused by mutations in adipose triglyceride lipase/PNPLA2 or CGI-58/ABHD5.
abstract: Neutral lipid storage disease (NLSD) is a group of autosomal recessive disorders characterized by the excessive accumulation of neutral lipids in multiple tissues. Recently, two genes, adipose triglyceride lipase (ATGL/PNPLA2) and comparative gene identification-58 (CGI-58/ABHD5), have been shown to cause NLSD. ATGL specifically hydrolyzes the first fatty acid from triacylglycerols (TG) and CGI-58/ABHD5 stimulates ATGL activity by a currently unknown mechanism. Mutations in both the ATGL and the CGI-58 genes are associated with systemic TG accumulation, yet the resulting clinical manifestations are not identical. Patients with defective ATGL function suffer from more severe myopathy (NLSDM) than patients with defective CGI-58 function. On the other hand, CGI-58 mutations are always associated with ichthyosis (NLSDI), which was not observed in patients with defective ATGL function. These observations indicate an ATGL-independent function of CGI-58. This review summarizes recent findings with the goal of relating structural variants of ATGL and CGI-58 to functional consequences in lipid metabolism.
authors.affiliation: Institute of Molecular Biosciences, University of Graz, Graz, Austria.
authors.forename: Martina
authors.initials: M
authors.lastname: Schweiger
authors.forename: Achim
authors.initials: A
authors.lastname: Lass
authors.forename: Robert
authors.initials: R
authors.lastname: Zimmermann
authors.forename: Thomas O
authors.initials: TO
authors.lastname: Eichmann
authors.forename: Rudolf
authors.initials: R
authors.lastname: Zechner
mesh_terms: D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase; D000818:Animals; D006801:Humans; D008049:Lipase / Q000235:genetics* / Q000502:physiology; D008052:Lipid Metabolism, Inborn Errors / Q000150:complications / Q000235:genetics*; D008954:Models, Biological; D009154:Mutation / Q000502:physiology; D000217:Acyltransferases
chemical_list: D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase; D008049:Lipase; C439972:ABHD5 protein, human; C494794:PNPLA2 protein, human; D000217:Acyltransferases