Introduction: The PNPLA2 gene encodes the enzyme adipose triglyceride lipase (ATGL), which catalyzes the first step of triglyceride hydrolysis. Mutations in this gene are associated with an autosomal recessive lipid-storage myopathy, neutral lipid-storage disease with myopathy (NLSD-M). Results: A 72-year-old woman had late-onset myopathy, with mild weakness, cramps, and exercise intolerance. Electromyography showed myotonic discharges. A few leukocytes showed lipid droplets (Jordan anomaly). Deltoid and quadriceps muscle biopsies showed no lipid storage. Genetic analysis of PNPLA2 detected 2 heterozygous mutations: c.497A>G (p.Asp166Gly) in exon 5 and c.1442C>T (p.Pro481Leu) in exon 10. Expression of mutant PNPLA2 plasmids in HeLa cells resulted in impaired enzyme activity, confirming the pathological effects of the mutations. Conclusions: In this case of NLSD-M, the myopathy may be due to a metabolic defect rather than to a mechanical effect of lipid storage. This suggests that more than 1 mechanism contributes to muscle damage in NLSD-M.

Pennisi, E. M., Missaglia, S., Dimauro, S., Bernardi, C., Akman, H. O., Tavian, D., A myopathy with unusual features caused by PNPLA2 gene mutations, <<MUSCLE & NERVE>>, 2015; 51 (4): 609-613. [doi:10.1002/mus.24477] [http://hdl.handle.net/10807/66048]

A myopathy with unusual features caused by PNPLA2 gene mutations

Missaglia, Sara;Tavian, Daniela
2015

Abstract

Introduction: The PNPLA2 gene encodes the enzyme adipose triglyceride lipase (ATGL), which catalyzes the first step of triglyceride hydrolysis. Mutations in this gene are associated with an autosomal recessive lipid-storage myopathy, neutral lipid-storage disease with myopathy (NLSD-M). Results: A 72-year-old woman had late-onset myopathy, with mild weakness, cramps, and exercise intolerance. Electromyography showed myotonic discharges. A few leukocytes showed lipid droplets (Jordan anomaly). Deltoid and quadriceps muscle biopsies showed no lipid storage. Genetic analysis of PNPLA2 detected 2 heterozygous mutations: c.497A>G (p.Asp166Gly) in exon 5 and c.1442C>T (p.Pro481Leu) in exon 10. Expression of mutant PNPLA2 plasmids in HeLa cells resulted in impaired enzyme activity, confirming the pathological effects of the mutations. Conclusions: In this case of NLSD-M, the myopathy may be due to a metabolic defect rather than to a mechanical effect of lipid storage. This suggests that more than 1 mechanism contributes to muscle damage in NLSD-M.
Inglese
Pennisi, E. M., Missaglia, S., Dimauro, S., Bernardi, C., Akman, H. O., Tavian, D., A myopathy with unusual features caused by PNPLA2 gene mutations, <<MUSCLE & NERVE>>, 2015; 51 (4): 609-613. [doi:10.1002/mus.24477] [http://hdl.handle.net/10807/66048]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/66048
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