Neutral lipid storage disease with myopathy: A 10-year follow-up case report
https://doi.org/10.4081/ejtm.2022.10645
Accepted: 11 June 2022
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Mutations in PNPLA2 gene encoding for adipose triglyceride lipase (ATGL), involved in triglyceride degradation, lead to an inborn error of neutral lipid metabolism. The disorder that results in abnormal storage of neutral lipid is known as neutral lipid storage disease with myopathy (NLSDM). We report the follow-up of a 30-year-old woman with NLSDM, asymptomatic until age 23. At the age of 18, a high level of CPK and neutral lipid abnormal accumulation in muscle and skin cells suggested NLSDM diagnosis, afterwards confirmed by PNPLA2 analysis. After 5 years, she developed weakness in the upper and lower extremities. She was put on a low-fat diet with medium-chain triglycerides (MCT) oil supplementation but, although her CPK level decreased, myopathy continued to progress. At present, she presents severe skeletal myopathy without cardiac involvement. In this patient, no beneficial effects on progressive skeletal muscle weakness were detected after the MCT diet, probably due to complete loss of PNPLA2 expression.
Angelini C, Pennisi E, Missaglia S, Tavian D. Metabolic lipid muscle disorders: biomarkers and treatment. Ther Adv Neurol Disord 2019 Apr;12:1756286419843359. eCollection 2019. DOI: https://doi.org/10.1177/1756286419843359
Tavian D, Maggi L, Mora M, Morandi L, Bragato C, Missaglia S. A novel PNPLA2 mutation causing total loss of RNA and protein expression in two NLSDM siblings with early onset but slowly progressive severe myopathy. Genes Dis. 2019 Jul;8(1):73-8. eCollection 2021 Jan. DOI: https://doi.org/10.1016/j.gendis.2019.07.006
Missaglia S, Coleman RA, Mordente A, Tavian D. Neutral lipid storage diseases as cellular model to study lipid droplet function. Cells. 2019 Feb;8(2),E187. DOI: https://doi.org/10.3390/cells8020187
Higashi M, Hirano K, Kobayashi K, Yoshihiko I, Issiki A, Otsuka T, Suzuki C, Nakamura H, Nagasaka H, Miyata T, Miyamoto Y, Kobayashi K, Naito H, Toda T. Distinct cardiac phenotype between two homozygotes born in a village with accumulation of a genetic deficiency of adipose triglyceride lipase. Int J Cardiol. 2015 Aug;192:30-2. Epub 2015 May 6. DOI: https://doi.org/10.1016/j.ijcard.2015.05.004
Reilich P, Horvath R, Krause S, Schramm N, Turnbull DM, Trenell M, Holligsworth KG, Gorman GS, Hans VH, Reimann J, MacMillan A, Turner L, Schollen A, Witte G, Czermin B, Holinski-Feder E, Walter MC, Schoser B, Lochmuller H. The phenotypic spectrum of neutral lipid storage myopathy due to mutations in the PNPLA2 gene. J Neurol. 2011 Nov;258(11):1987-97. Epub 2011 May 5. DOI: https://doi.org/10.1007/s00415-011-6055-4
Pennisi EM, Arca M, Bertini E, Bruno C, Cassandrini D, D’Amico A, Garibaldi M, Gragnani F, Maggi L, Massa R, Missaglia S, Morandi L, Tasca E, Tavian D, Toscano A, Angelini C, Italian NLSD Group. Neutral Lipid Storage Diseases: clinical/genetic features and natural history in a large cohort of Italian patients. Orphanet J Rare Dis. 2017 May;12(1):90. DOI: https://doi.org/10.1186/s13023-017-0646-9
Zhang W, Wen B, Lu J, Zhao Y, Hong D, Zhao Z, Zhang C, Luo Y, Qi X, Zhang Y, Song X, Zhao Y, Zhao C, Hu J, Yang H, Wang Z, Yan C, Yuan Y. Neutral lipid storage disease with myopathy in China: a large multicentric cohort study. Orphanet J Rare Dis. 2019 Oct;14(1):234. DOI: https://doi.org/10.1186/s13023-019-1209-z
Fischer J, Lefèvre C, Morava E, Mussini JM, Laforet P, Negre-Salvayre A, Lathrop M, Salvayre R. The gene encoding adipose triglyceride lipase (PNPLA2) is mutated in neutral lipid storage disease with myopathy. Nat Genet. 2007 Jan;39(1):28-30. Epub 2006 Dec 24. DOI: https://doi.org/10.1038/ng1951
Chen J, Hong D, Wang Z, Yuan Y. A novel PNPLA2 mutation causes neutral lipid storage disease with myopathy (NLSDM) presenting muscular dystrophic features with lipid storage and rimmed vacuoles. Clin Neuropathol. 2010 Nov-Dec;29(6):351-6. DOI: https://doi.org/10.5414/NPP29351
Tavian D, Missaglia S, Redaelli C, Pennisi EM, Invernici G, Wessalowski R, Maiwald R, Arca M, Coleman RA. Contribution of novel ATGL missense mutations to the clinical phenotype of NLSD-M: a strikingly low amount of lipase activity may preserve cardiac function. Hum Mol Genet. 2012 Dec;21(24):5318-28. Epub 2012 Sep 17. DOI: https://doi.org/10.1093/hmg/dds388
Missaglia S, Tasca E, Angelini C, Moro L, Tavian D. Novel missense mutations in PNPLA2 causing late onset and clinical heterogeneity of neutral lipid storage disease with myopathy in three siblings. Mol Genet Metab. 2015 Jun-Jul;115(2-3):110-7. Epub 2015 May 2. DOI: https://doi.org/10.1016/j.ymgme.2015.05.001
Akman HO, Davidzon G, Tanji K, Macdermott EJ, Larsen L, Davidson MM, Haller RG, Szczepaniak LS, Lehman TJA, Hirano M, DiMauro S. Neutral lipid storage disease with subclinical myopathy due to a retrotransposal insertion in the PNPLA2 gene. Neuromuscul Disord. 2010 Jun;20(6):397-402. Epub 2010 May 14. DOI: https://doi.org/10.1016/j.nmd.2010.04.004
Lin P, Li W, Wen B, Zhao Y, Fenster DS, Wang Y, Gong Y, Yan C. Novel PNPLA2 gene mutations in Chinese Han patients causing neutral lipid storage disease with myopathy. J Hum Genet. 2012 Oct;57(10):679-81. Epub 2012 Jul 26. DOI: https://doi.org/10.1038/jhg.2012.84
Xu C, Zhao Y, Liu J, Zhang W, Wang Z, Yuan Y. Muscle MRI in neutral lipid storage disease with myopathy carrying mutationc 187fl1G>A. Musc Nerve. 2015 Jun;51(6):922-7. Epub 2015 Apr 24. DOI: https://doi.org/10.1002/mus.24507
Pasanisi MB, Missaglia S, Cassandrini D, Salerno F, Farina S, Andreini D, Agostoni P, Morandi L, Mora M, Tavian D. Severe cardiomyopathy in a young patient with complete deficiency of adipose triglyceride lipase due to a novel mutation in PNPLA2 gene. Int J Cardiol. 2016 Mar;207:165-7. Epub 2016 Jan 9. DOI: https://doi.org/10.1016/j.ijcard.2016.01.137
Missaglia S, Maggi L, Mora M, Gibertini S, Blasevich F, Agostoni P, Moro L, Cassandrini D, Santorelli FM, Gerevini S, Tavian D. Late onset of neutral lipid storage disease due to novel PNPLA2 mutations causing a total loss of lipase activity in a patient with myopathy and slight cardiac involvement. Neuromuscul Disord. 2017 May;27(5):481-6. Epub 2017 Jan 17. DOI: https://doi.org/10.1016/j.nmd.2017.01.011
Pedersen BK. Anti-inflammatory effects of exercise: role in diabetes and cardiovascular disease. Eur J Clin Invest. 2017 Aug;47(8):600-11. Epub 2017 Jul 19. DOI: https://doi.org/10.1111/eci.12781
Merritt JL 2nd, Norris M, Kanungo S. Fatty acid oxidation disorders. Ann Transl Med. 2018 Dec;6(24):473. DOI: https://doi.org/10.21037/atm.2018.10.57
Biswas D, Ghosh M, Kumar S, Chakrabarti P. PPARα-ATGL pathway improves muscle mitochondrial metabolism: implication in aging. FASEB J. 2016 Nov;30(11):3822-34. Epub 2016 Aug 2. DOI: https://doi.org/10.1096/fj.201600571RR
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