title: Symptomatic lipid storage in carriers for the PNPLA2 gene.
abstract: Neutral lipid storage disease comprises a heterogeneous group of inherited disorders characterized by severe accumulation of cytoplasmic triglyceride droplets in several tissues and neutrophils. A novel type of autosomal recessive lipid myopathy due to PNPLA2 mutations was recently described with associated cardiac disease, myopathy and frequent infections, but without ichthyosis. Here we describe the clinical and biochemical characteristics of a long surviving patient and report on four carrier family members with diverse clinical involvement. Interestingly, heterozygous patients show neutral lipid storage in muscle and in the keratocytes of the skin, Jordans' bodies, mild myopathy and frequent infections. Biochemical analysis of fibroblasts obtained from patients revealed increased triglyceride storage and reduced lipid droplet-associated triglyceride hydrolase activity. Together, our data implicate that the wild-type allele cannot fully compensate for the mutated dysfunctional allele of PNPLA2 leading to triglyceride accumulation in muscle and mild myopathy in PNPLA2 mutation carriers. The presence of neutral lipid droplets in the skin in PNPLA2 mutation carriers strengthens the link between NLSD and other neutral lipid storage diseases with ichthyosis.
authors.affiliation: Department of Internal Medicine, Radboud University Medical Centre Nijmegen, Nijmegen, The Netherlands.
authors.forename: Mirian C H
authors.initials: MC
authors.lastname: Janssen
authors.forename: Baziel
authors.initials: B
authors.lastname: van Engelen
authors.forename: Livia
authors.initials: L
authors.lastname: Kapusta
authors.forename: Martin
authors.initials: M
authors.lastname: Lammens
authors.forename: Martin
authors.initials: M
authors.lastname: van Dijk
authors.forename: Judith
authors.initials: J
authors.lastname: Fischer
authors.forename: Marinette
authors.initials: M
authors.lastname: van der Graaf
authors.forename: Ron A
authors.initials: RA
authors.lastname: Wevers
authors.forename: Manuela
authors.initials: M
authors.lastname: Fahrleitner
authors.forename: Robert
authors.initials: R
authors.lastname: Zimmermann
authors.forename: Eva
authors.initials: E
authors.lastname: Morava
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005192:Family Health; D005260:Female; D006579:Heterozygote; D006801:Humans; D008049:Lipase / Q000235:genetics*; D008052:Lipid Metabolism, Inborn Errors / Q000235:genetics*; D008297:Male; D008854:Microscopy, Electron; D009132:Muscles / Q000378:metabolism / Q000648:ultrastructure; D009135:Muscular Diseases / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D000217:Acyltransferases
chemical_list: D008049:Lipase; C494794:PNPLA2 protein, human; D000217:Acyltransferases