The Lack of the C-Terminal Domain of Adipose Triglyceride Lipase Causes Neutral Lipid Storage Disease through Impaired Interactions with Lipid Droplets

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.

Download Full-text

Metabolic Consequences of Adipose Triglyceride Lipase Deficiency in Humans: An In Vivo Study in Patients With Neutral Lipid Storage Disease With Myopathy

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2013-1444 ◽

2013 ◽

Vol 98 (9) ◽

pp. E1540-E1548 ◽

Cited By ~ 18

Author(s):

Andrea Natali ◽

Amalia Gastaldelli ◽

Stefania Camastra ◽

Simona Baldi ◽

Fabiana Quagliarini ◽

...

Keyword(s):

Neutral Lipid ◽

Storage Disease ◽

Lipid Storage ◽

In Vivo Study ◽

Adipose Triglyceride Lipase ◽

Lipid Storage Disease ◽

Triglyceride Lipase ◽

Neutral Lipid Storage Disease

Download Full-text

Peripheral leukocyte anomaly detected with routine automated hematology analyzer sensitive to adipose triglyceride lipase deficiency manifesting neutral lipid storage disease with myopathy/triglyceride deposit cardiomyovasculopathy

Molecular Genetics and Metabolism Reports ◽

10.1016/j.ymgmr.2014.05.001 ◽

2014 ◽

Vol 1 ◽

pp. 249-253 ◽

Cited By ~ 5

Author(s):

Akira Suzuki ◽

Hironori Nagasaka ◽

Yasuhiro Ochi ◽

Kazuhiro Kobayashi ◽

Hiroshi Nakamura ◽

...

Keyword(s):

Neutral Lipid ◽

Storage Disease ◽

Lipid Storage ◽

Adipose Triglyceride Lipase ◽

Lipid Storage Disease ◽

Triglyceride Lipase ◽

Peripheral Leukocyte ◽

Hematology Analyzer ◽

Neutral Lipid Storage Disease ◽

Automated Hematology Analyzer

Download Full-text

Neutral lipid storage disease with myopathy: Further phenotypic characterization of a rare PNPLA2 variant

Neuromuscular Disorders ◽

10.1016/j.nmd.2018.04.010 ◽

2018 ◽

Vol 28 (7) ◽

pp. 606-609 ◽

Cited By ~ 3

Author(s):

Caitlin S. Latimer ◽

Jennifer Schleit ◽

Adam Reynolds ◽

Desiree A. Marshall ◽

Benjamin Podemski ◽

...

Keyword(s):

Neutral Lipid ◽

Storage Disease ◽

Lipid Storage ◽

Phenotypic Characterization ◽

Lipid Storage Disease ◽

Neutral Lipid Storage Disease

Download Full-text

Neutral lipid storage disease

10.1007/springerreference_41937 ◽

2011 ◽

Keyword(s):

Neutral Lipid ◽

Storage Disease ◽

Lipid Storage ◽

Lipid Storage Disease ◽

Neutral Lipid Storage Disease

Download Full-text

Neutral Lipid Storage Disease Associated with the PNPLA2 Gene: Case Report and Literature Review

European Neurology ◽

10.1159/000508346 ◽

2020 ◽

Vol 83 (3) ◽

pp. 317-322

Author(s):

Makoto Samukawa ◽

Naoko Nakamura ◽

Makito Hirano ◽

Miyuki Morikawa ◽

Hanami Sakata ◽

...

Keyword(s):

Neutral Lipid ◽

Storage Disease ◽

Clinical Laboratory ◽

Lipid Storage ◽

Compound Heterozygous ◽

Homozygous Mutation ◽

Lipid Storage Disease ◽

Consistent Finding ◽

Pulmonary Cysts ◽

Neutral Lipid Storage Disease

Mutations in the PNPLA2 gene cause neutral lipid storage disease with myopathy (NLSDM) or triglyceride deposit cardiomyovasculopathy. We report a detailed case study of a 53-year-old man with NLSDM. The PNPLA2 gene was analyzed according to the reported method. We summarized the clinical, laboratory, and genetic information of 56 patients, including our patient and 55 other reported patients with homozygous or compound heterozygous mutations in the PNPLA2 gene. We found a novel homozygous mutation (c.194delC) in the PNPLA2 gene that resulted in frameshift. The patient suffered from normal-tension glaucoma and pulmonary cysts, symptoms that are relatively common in the elderly but were not previously reported for this disease. Our summary confirmed that Jordan’s anomaly, polymorphonuclear leukocytes with lipid accumulation, was the most consistent finding of this disease. Because this disease is potentially treatable, our results may help rapid and correct diagnosis.

Download Full-text