TY - JOUR
T1 - Symptomatic lipid storage in carriers for the PNPLA2 gene
AU - Janssen, Mirian C.H.
AU - Van Engelen, Baziel
AU - Kapusta, Livia
AU - Lammens, Martin
AU - Van Dijk, Martin
AU - Fischer, Judith
AU - Van Der Graaf, Marinette
AU - Wevers, Ron A.
AU - Fahrleitner, Manuela
AU - Zimmermann, Robert
AU - Morava, Eva
PY - 2013/8
Y1 - 2013/8
N2 - 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.
AB - 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.
KW - Deafness
KW - Implantable cardioverter-defibrillator
KW - Insulin resistance
KW - Lipid myopathy
KW - Neutral lipid storage
KW - Symptomatic carriers
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U2 - 10.1038/ejhg.2012.256
DO - 10.1038/ejhg.2012.256
M3 - Article
C2 - 23232698
AN - SCOPUS:84880919361
SN - 1018-4813
VL - 21
SP - 807
EP - 815
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
IS - 8
ER -