Key result
Heterozygous mutations in the PNPLA2 gene caused late-onset myopathy with impaired enzyme activity but no lipid storage in muscle biopsies.
Case Report (n=1)
PNPLA2 gene mutations can cause neutral lipid-storage disease with myopathy (NLSD-M) without visible lipid storage in muscle biopsies, suggesting a metabolic defect mechanism.
May prompt PNPLA2 testing in unexplained late-onset myopathy; leaves open phenotypic spectrum and validation studies.
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.
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Pennisi et al. (2014) conducted a case report in Neutral lipid-storage disease with myopathy (NLSD-M) (n=1). PNPLA2 gene mutations was evaluated on Clinical and pathological features. Heterozygous mutations in the PNPLA2 gene caused late-onset myopathy with impaired enzyme activity but no lipid storage in muscle biopsies.
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