Neutral lipid storage disease: genetic disorders caused by mutations in adipose triglyceride lipase/PNPLA2 or CGI-58/ABHD5

作者：Schweiger Martina; Lass Achim; Zimmermann Robert; Eichmann Thomas O; Zechner Rudolf^*

来源：American Journal of Physiology - Endocrinology And Metabolism, 2009, 297(2): E289-E296.

DOI：10.1152/ajpendo.00099.2009

• ichthyosis
• myopathy
• Jordans' anomaly
• Chanarin-Dorfman syndrome
• lipolysis

Schweiger M, Lass A, Zimmermann R, Eichmann TO, Zechner R. Neutral lipid storage disease: genetic disorders caused by mutations in adipose triglyceride lipase/PNPLA2 or CGI-58/ABHD5. Am J Physiol Endocrinol Metab 297: E289 E296, 2009. First published April 28, 2009; doi: 10.1152/ajpendo.00099.2009. 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.

• 出版日期2009-8