465
Views
29
CrossRef citations to date
0
Altmetric
Review

Familial Partial Lipodystrophy (FPLD): Recent Insights

, , &
Pages 1531-1544 | Published online: 06 May 2020

References

  • Chiquette E, Oral EA, Garg A, Araújo-Vilar D, Dhankhar P. Estimating the prevalence of generalized and partial lipodystrophy: findings and challenges. Diabetes Metab Syndr Obes. 2017;10:375. doi:10.2147/DMSO.S130810
  • Köbberling J, Willms B, Kattermann R, Creutzfeldt W. Lipodystrophy of the extremities. A dominantly inherited syndrome associated with lipatrophic diabetes. Humangenetik. 1975;29(2):111–120. doi:10.1007/bf00430347
  • Dunnigan MG, Cochrane MA, Kelly A, Scott JW. Familial lipoatrophic diabetes with dominant transmission: a new syndrome. QJM. 1974;43(1):33–48.
  • Araújo-Vilar D, Santini F. Diagnosis and treatment of lipodystrophy: a step-by-step approach. J Endocrinol Invest. 2019;42(1):61–73. doi:10.1007/s40618-018-0887-z
  • Melvin A, Stears A, Savage DB. Recent developments in lipodystrophy. Curr Opin Lipidol. 2019;30(4):284–290. doi:10.1097/MOL.0000000000000613
  • Hussain I, Garg A. Lipodystrophy syndromes. Endocrinol Metab Clin. 2016;45(4):783–797. doi:10.1016/j.ecl.2016.06.012
  • Vigouroux C, Caron-Debarle M, Le Dour C, Magré J, Capeau J. Molecular mechanisms of human lipodystrophies: from adipocyte lipid droplet to oxidative stress and lipotoxicity. Int J Biochem Cell Biol. 2011;43(6):862–876. doi:10.1016/j.biocel.2011.03.002
  • Huang-Doran I, Sleigh A, Rochford JJ, O’Rahilly S, Savage DB. Lipodystrophy: metabolic insights from a rare disorder. J Endocrinol. 2010;207(3):245–255. doi:10.1677/JOE-10-0272
  • Virtue S, Vidal-Puig A. It’s not how fat you are, it’s what you do with it that counts. PLoS Biol. 2008;6(9):e237. doi:10.1371/journal.pbio.0060237
  • Wong SPY, Huda M, English P, et al. Adipokines and the insulin resistance syndrome in familial partial lipodystrophy caused by a mutation in lamin A/C. Diabetologia. 2005;48(12):2641–2649. doi:10.1007/s00125-005-0038-x
  • Haque WA, Shimomura I, Matsuzawa Y, Garg A. Serum adiponectin and leptin levels in patients with lipodystrophies. J Clin Endocrinol Metab. 2002;87(5):2395–2398. doi:10.1210/jcem.87.5.8624
  • Blüher M, Mantzoros CS. From leptin to other adipokines in health and disease: facts and expectations at the beginning of the 21st century. Metabolism. 2015;64(1):131–145. doi:10.1016/j.metabol.2014.10.016
  • Sarmento ASC, Lima JG, de Souza Timoteo AR, et al. Changes in redox and endoplasmic reticulum homeostasis are related to congenital generalized lipodystrophy type 2. Biochim Biophys Acta Mol Cell Biol Lipids. 2020;158610.
  • Mathew H, Castracane VD, Mantzoros C. Adipose tissue and reproductive health. Metabolism. 2018;86:18–32. doi:10.1016/j.metabol.2017.11.006
  • Kawwass JF, Summer R, Kallen CB. Direct effects of leptin and adiponectin on peripheral reproductive tissues: a critical review. Mol Hum Reprod. 2015;21(8):617–632. doi:10.1093/molehr/gav025
  • Dib K, Whitehead JP, Humphreys PJ, et al. Impaired activation of phosphoinositide 3-kinase by insulin in fibroblasts from patients with severe insulin resistance and pseudoacromegaly. A disorder characterized by selective postreceptor insulin resistance. J Clin Invest. 1998;101(5):1111–1120. doi:10.1172/JCI119884
  • Lotta LA, Wittemans LBL, Zuber V, et al. Association of genetic variants related to gluteofemoral vs abdominal fat distribution with type 2 diabetes, coronary disease, and cardiovascular risk factors. JAMA. 2018;320(24):2553–2563. doi:10.1001/jama.2018.19329
  • Lotta LA, Gulati P, Day FR, et al. Integrative genomic analysis implicates limited peripheral adipose storage capacity in the pathogenesis of human insulin resistance. Nat Genet. 2017;49(1):17. doi:10.1038/ng.3714
  • Broekema MF, Savage DB, Monajemi H, Kalkhoven E. Gene-gene and gene-environment interactions in lipodystrophy: lessons learned from natural PPARγ mutants. Biochim Biophys Acta Mol Cell Biol Lipids. 2019.
  • Campeau PM, Astapova O, Martins R, et al. Clinical and molecular characterization of a severe form of partial lipodystrophy expanding the phenotype of PPARγ deficiency. J Lipid Res. 2012;53(9):1968–1978. doi:10.1194/jlr.P025437
  • Hegele RA, Cao H, Frankowski C, Mathews ST, Leff T. PPARG F388L, a transactivation-deficient mutant, in familial partial lipodystrophy. Diabetes. 2002;51(12):3586–3590. doi:10.2337/diabetes.51.12.3586
  • Strissel KJ, Stancheva Z, Miyoshi H, et al. Adipocyte death, adipose tissue remodeling, and obesity complications. Diabetes. 2007;56(12):2910–2918. doi:10.2337/db07-0767
  • Sears IB, MacGinnitie MA, Kovacs LG, Graves RA. Differentiation-dependent expression of the brown adipocyte uncoupling protein gene: regulation by peroxisome proliferator-activated receptor gamma. Mol Cell Biol. 1996;16(7):3410–3419. doi:10.1128/MCB.16.7.3410
  • Okuno A, Tamemoto H, Tobe K, et al. Troglitazone increases the number of small adipocytes without the change of white adipose tissue mass in obese Zucker rats. J Clin Invest. 1998;101(6):1354–1361. doi:10.1172/JCI1235
  • Kelly IE, Han TS, Walsh K, Lean ME. Effects of a thiazolidinedione compound on body fat and fat distribution of patients with type 2 diabetes. Diabetes Care. 1999;22(2):288–293. doi:10.2337/diacare.22.2.288
  • Agarwal AK, Barnes RI, Garg A. Genetic basis of congenital generalized lipodystrophy. Int J Obes. 2004;28(2):336. doi:10.1038/sj.ijo.0802487
  • Shackleton S, Lloyd DJ, Jackson SNJ, et al. LMNA, encoding lamin A/C, is mutated in partial lipodystrophy. Nat Genet. 2000;24(2):153. doi:10.1038/72807
  • Garg A. Lipodystrophies: genetic and acquired body fat disorders. J Clin Endocrinol Metab. 2011;96(11):3313–3325. doi:10.1210/jc.2011-1159
  • Garg A, Peshock RM, Fleckenstein JL. Adipose tissue distribution pattern in patients with familial partial lipodystrophy (Dunnigan variety). J Clin Endocrinol Metab. 1999;84(1):170–174.
  • Patni N, Li X, Adams-Huet B, Vasandani C, Gomez-Diaz RA, Garg A. Regional body fat changes and metabolic complications in children with Dunnigan lipodystrophy-causing LMNA variants. J Clin Endocrinol Metab. 2018;104(4):1099–1108. doi:10.1210/jc.2018-01922
  • Vantyghem MC, Pigny P, Maurage CA, et al. Patients with familial partial lipodystrophy of the Dunnigan type due to a LMNA R482W mutation show muscular and cardiac abnormalities. J Clin Endocrinol Metab. 2004;89(11):5337–5346. doi:10.1210/jc.2003-031658
  • Pasotti M, Klersy C, Pilotto A, et al. Long-term outcome and risk stratification in dilated cardiolaminopathies. J Am Coll Cardiol. 2008;52(15):1250–1260. doi:10.1016/j.jacc.2008.06.044
  • Fountas A, Giotaki Z, Dounousi E, et al. Familial partial lipodystrophy and proteinuric renal disease due to a missense c. 1045C> T LMNA mutation. Endocrinol Diabetes Metab Case Rep. 2017;2017(1). doi:10.1530/EDM-17-0049
  • Simha V, Agarwal AK, Oral EA, Fryns J-P, Garg A. Genetic and phenotypic heterogeneity in patients with mandibuloacral dysplasia-associated lipodystrophy. J Clin Endocrinol Metab. 2003;88(6):2821–2824. doi:10.1210/jc.2002-021575
  • Spear ED, Hsu E-T, Nie L, Carpenter EP, Hrycyna CA, Michaelis S. ZMPSTE24 missense mutations that cause progeroid diseases decrease prelamin A cleavage activity and/or protein stability. Dis Model Mech. 2018;11(7):dmm033670. doi:10.1242/dmm.033670
  • Cassini TA, Robertson AK, Bican AG, et al. Phenotypic heterogeneity of ZMPSTE24 deficiency. Am J Med Genet A. 2018;176(5):1175–1179. doi:10.1002/ajmg.a.38493
  • Agarwal AK, Fryns J-P, Auchus RJ, Garg A. Zinc metalloproteinase, ZMPSTE24, is mutated in mandibuloacral dysplasia. Hum Mol Genet. 2003;12(16):1995–2001. doi:10.1093/hmg/ddg213
  • Gonzalo S, Kreienkamp R, Askjaer P. Hutchinson-Gilford progeria syndrome: a premature aging disease caused by LMNA gene mutations. Ageing Res Rev. 2017;33:18–29. doi:10.1016/j.arr.2016.06.007
  • Bonne G, Yaou RB, Navarro C, et al. Type B mandibuloacral dysplasia with congenital myopathy due to homozygous ZMPSTE24 missense mutation. Eur J Hum Genet. 2011;19(6):647–654. doi:10.1038/ejhg.2010.256
  • Kwan JM, Satter EK. A 53-year-old woman with multifocal subcutaneous nodules. J Am Acad Dermatol. 2015;72(5):924–926. doi:10.1016/j.jaad.2012.06.032
  • Agarwal AK, Zhou XJ, Hall RK, et al. Focal segmental glomerulosclerosis in patients with mandibuloacral dysplasia owing to ZMPSTE24 deficiency. J Investigat Med. 2006;54(4):208–213. doi:10.2310/6650.2006.05068
  • George S, Rochford JJ, Wolfrum C, et al. A family with severe insulin resistance and diabetes due to a mutation in AKT2. Science. 2004;304(5675):1325–1328. doi:10.1126/science.1096706
  • Klatka M, Rysz I, Kozyra K, Polak A, Kołłątaj W. SHORT syndrome in a two-year-old girl–case report. Ital J Pediatr. 2017;43(1):44. doi:10.1186/s13052-017-0362-z
  • Thauvin-Robinet C, Auclair M, Duplomb L, et al. PIK3R1 mutations cause syndromic insulin resistance with lipoatrophy. Am J Hum Genet. 2013;93(1):141–149. doi:10.1016/j.ajhg.2013.05.019
  • Dyment DA, Smith AC, Alcantara D, et al. Mutations in PIK3R1 cause SHORT syndrome. Am J Hum Genet. 2013;93(1):158–166. doi:10.1016/j.ajhg.2013.06.005
  • Alcantara D, Elmslie F, Tetreault M, et al. SHORT syndrome due to a novel de novo mutation in PRKCE (Protein Kinase Cɛ) impairing TORC2-dependent AKT activation. Hum Mol Genet. 2017;26(19):3713–3721. doi:10.1093/hmg/ddx256
  • Chen FJ, Yin Y, Chua BT, Li P. CIDE family proteins control lipid homeostasis and the development of metabolic diseases. Traffic. 2020;21(1):94–105.
  • Rubio‐Cabezas O, Puri V, Murano I, et al. Partial lipodystrophy and insulin resistant diabetes in a patient with a homozygous nonsense mutation in CIDEC. EMBO Mol Med. 2009;1(5):280–287. doi:10.1002/emmm.200900037
  • Ajjaji D, Ben M’barek K, Mimmack ML, et al. Dual binding motifs underpin the hierarchical association of perilipins1–3 with lipid droplets. Mol Biol Cell. 2019;30(5):703–716. doi:10.1091/mbc.E18-08-0534
  • Jéru I, Vantyghem M-C, Bismuth E, et al. Diagnostic challenge in PLIN1-Associated familial partial lipodystrophy. J Clin Endocrinol Metab. 2019;104(12):6025–6032. doi:10.1210/jc.2019-00849
  • Laver TW, Patel KA, Colclough K, et al. PLIN1 haploinsufficiency is not associated with lipodystrophy. J Clin Endocrinol Metab. 2018;103(9):3225–3230. doi:10.1210/jc.2017-02662
  • Zolotov S, Xing C, Mahamid R, Shalata A, Sheikh‐Ahmad M, Garg A. Homozygous LIPE mutation in siblings with multiple symmetric lipomatosis, partial lipodystrophy, and myopathy. Am J Med Genet A. 2017;173(1):190–194. doi:10.1002/ajmg.a.37880
  • Albert JS, Yerges-Armstrong LM, Horenstein RB, et al. Null mutation in hormone-sensitive lipase gene and risk of type 2 diabetes. N Engl J Med. 2014;370(24):2307–2315. doi:10.1056/NEJMoa1315496
  • Garg A, Sankella S, Xing C, Agarwal AK. Whole-exome sequencing identifies ADRA2A mutation in atypical familial partial lipodystrophy. JCI Insight. 2016;1(9). doi:10.1172/jci.insight.86870
  • Garg A, Agarwal AK. Caveolin-1: A New Locus for Human Lipodystrophy. Oxford University Press; 2008.
  • Kim CA, Delépine M, Boutet E, et al. Association of a homozygous nonsense caveolin-1 mutation with Berardinelli-Seip congenital lipodystrophy. J Clin Endocrinol Metab. 2008;93(4):1129–1134. doi:10.1210/jc.2007-1328
  • Garg A, Kircher M, Del Campo M, Amato RS, Agarwal AK, University of Washington Center for Mendelian G. Whole exome sequencing identifies de novo heterozygous CAV1 mutations associated with a novel neonatal onset lipodystrophy syndrome. Am J Med Genet A. 2015;167(8):1796–1806. doi:10.1002/ajmg.a.37115
  • Cao H, Alston L, Ruschman J, Hegele RA. Heterozygous CAV1 frameshift mutations (MIM 601047) in patients with atypical partial lipodystrophy and hypertriglyceridemia. Lipids Health Dis. 2008;7(1):3. doi:10.1186/1476-511X-7-3
  • Yamamoto GL, Baratela WAR, Almeida TF, et al. Mutations in PCYT1A cause spondylometaphyseal dysplasia with cone-rod dystrophy. Am J Hum Genet. 2014;94(1):113–119. doi:10.1016/j.ajhg.2013.11.022
  • Hoover-Fong J, Sobreira N, Jurgens J, et al. Mutations in PCYT1A, encoding a key regulator of phosphatidylcholine metabolism, cause spondylometaphyseal dysplasia with cone-rod dystrophy. Am J Hum Genet. 2014;94(1):105–112. doi:10.1016/j.ajhg.2013.11.018
  • Liu Y, Ramot Y, Torrelo A, et al. Mutations in proteasome subunit β type 8 cause chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature with evidence of genetic and phenotypic heterogeneity. Arthritis Rheum. 2012;64(3):895–907. doi:10.1002/art.33368
  • Torrelo A. CANDLE syndrome as a paradigm of proteasome-related autoinflammation. Front Immunol. 2017;8:927. doi:10.3389/fimmu.2017.00927
  • Yu C-E, Oshima J, Fu Y-H, et al. Positional cloning of the Werner’s syndrome gene. Science. 1996;272(5259):258–262. doi:10.1126/science.272.5259.258
  • Oshima J, Sidorova JM, Monnat JRJ. Werner syndrome: clinical features, pathogenesis and potential therapeutic interventions. Ageing Res Rev. 2017;33:105–114. doi:10.1016/j.arr.2016.03.002
  • Weedon MN, Ellard S, Prindle MJ, et al. An in-frame deletion at the polymerase active site of POLD1 causes a multisystem disorder with lipodystrophy. Nat Genet. 2013;45(8):947. doi:10.1038/ng.2670
  • Cunniff C, Bassetti JA, Ellis NA. Bloom’s syndrome: clinical spectrum, molecular pathogenesis, and cancer predisposition. Mol Syndromol. 2017;8(1):4–23. doi:10.1159/000452082
  • Sanz MM, German J, Cunniff C. Bloom’s Syndrome Mar 22 [Updated 2016 Apr 7]. In: Pagon RA, Adam MP, Ardinger HH, et al, editors. GeneReviews® [Internet]. Seattle, WA, USA:University of Washington; 2006:1993–2017.
  • Köbberling J, Dunnigan MG. Familial partial lipodystrophy: two types of an X linked dominant syndrome, lethal in the hemizygous state. J Med Genet. 1986;23(2):120–127. doi:10.1136/jmg.23.2.120
  • Herbst KL, Tannock LR, Deeb SS, Purnell JQ, Brunzell JD, Chait A. Köbberling type of familial partial lipodystrophy: an underrecognized syndrome. Diabetes Care. 2003;26(6):1819–1824. doi:10.2337/diacare.26.6.1819
  • Stenson PD, Ball EV, Mort M, et al. Human gene mutation database (HGMD®): 2003 update. Hum Mutat. 2003;21(6):577–581. doi:10.1002/humu.10212
  • Brown RJ, Araujo-Vilar D, Cheung PT, et al. The diagnosis and management of lipodystrophy syndromes: a multi-society practice guideline. J Clin Endocrinol Metab. 2016;101(12):4500–4511. doi:10.1210/jc.2016-2466
  • Meral R, Ryan BJ, Malandrino N, et al. “Fat Shadows” from DXA for the qualitative assessment of lipodystrophy: when a picture is worth a thousand numbers. Diabetes Care. 2018;41(10):2255–2258. doi:10.2337/dc18-0978
  • Lewandowski KC, Dąbrowska K, Brzozowska M, Kawalec J, Lewiński A. Metformin paradoxically worsens insulin resistance in SHORT syndrome. Diabetol Metab Syndr. 2019;11(1):81. doi:10.1186/s13098-019-0477-z
  • Arioglu E, Duncan-Morin J, Sebring N, et al. Efficacy and safety of troglitazone in the treatment of lipodystrophy syndromes. Ann Intern Med. 2000;133(4):263–274. doi:10.7326/0003-4819-133-4-200008150-00009
  • Simha V, Rao S, Garg A. Prolonged thiazolidinedione therapy does not reverse fat loss in patients with familial partial lipodystrophy, Dunnigan variety. Diabetes Obes Metab. 2008;10(12):1275–1276. doi:10.1111/j.1463-1326.2008.00978.x
  • Agostini M, Schoenmakers E, Beig J, et al. A pharmacogenetic approach to the treatment of patients with PPARG mutations. Diabetes. 2018;67(6):1086–1092. doi:10.2337/db17-1236
  • Banning F, Rottenkolber M, Freibothe I, Seissler J, Lechner A. Insulin secretory defect in familial partial lipodystrophy type 2 and successful long‐term treatment with a glucagon‐like peptide 1 receptor agonist. Diabet Med. 2017;34(12):1792–1794. doi:10.1111/dme.13527
  • Valerio CM, de Almeida JS, Moreira RO, et al. Dipeptidyl peptidase-4 levels are increased and partially related to body fat distribution in patients with familial partial lipodystrophy type 2. Diabetol Metab Syndr. 2017;9(1):26. doi:10.1186/s13098-017-0226-0
  • Oliveira J, Lau E, Carvalho D, Freitas P. Glucagon-like peptide-1 analogues-an efficient therapeutic option for the severe insulin resistance of lipodystrophic syndromes: two case reports. J Med Case Rep. 2017;11(1):12. doi:10.1186/s13256-016-1175-1
  • Ulahannan TJ, D’Emden M. Sustained, successful treatment of diabetes in lipodystrophy by dapagliflozin. 2018.
  • Hamaguchi T, Hirota Y, Takeuchi T, et al. Treatment of a case of severe insulin resistance as a result of a PIK 3R1 mutation with a sodium–glucose cotransporter 2 inhibitor. J Diabetes Investig. 2018;9(5):1224–1227. doi:10.1111/jdi.12825
  • Kawana Y, Imai J, Sawada S, Yamada T, Katagiri H. Sodium–glucose cotransporter 2 inhibitor improves complications of lipodystrophy: a case report. Ann Intern Med. 2017;166(6):450–451. doi:10.7326/L16-0372
  • Witztum JL, Gaudet D, Freedman SD, et al. Volanesorsen and triglyceride levels in familial chylomicronemia syndrome. N Engl J Med. 2019;381(6):531–542. doi:10.1056/NEJMoa1715944
  • Ciudin A, Baena‐Fustegueras JA, Fort JM, Encabo G, Mesa J, Lecube A. Successful treatment for the Dunnigan‐type familial partial lipodystrophy with Roux‐en‐Y gastric bypass. Clin Endocrinol. 2011;75(3):403. doi:10.1111/j.1365-2265.2011.04057.x
  • Utzschneider KM, Trence DL. Effectiveness of gastric bypass surgery in a patient with familial partial lipodystrophy. Diabetes Care. 2006;29(6):1380–1382. doi:10.2337/dc06-0130
  • Melvin A, Adams C, Flanagan C, et al. Roux-en-Y gastric bypass surgery in the management of familial partial lipodystrophy type 1. J Clin Endocrinol Metab. 2017;102(10):3616–3620. doi:10.1210/jc.2017-01235
  • Dollfus C, Blanche S, Trocme N, Funck‐Brentano I, Bonnet F, Levan P. Correction of facial lipoatrophy using autologous fat transplants in HIV‐infected adolescents. HIV Med. 2009;10(5):263–268. doi:10.1111/j.1468-1293.2008.00682.x
  • Neto B, Andrade G, Lima R, Barros M, Junior J. Surgical lipodystrophy correction associated with the use of antiretroviral therapy: an analysis of procedures performed and impact on the patients. Brasileira De Cirurgia Plástica. 2001;30(2):250–257.
  • Akinci B, Meral R, Oral EA. Update on therapeutic options in lipodystrophy. Curr Diab Rep. 2018;18(12):139. doi:10.1007/s11892-018-1100-7
  • Friedman JM, Mantzoros CS. 20 years of leptin: from the discovery of the leptin gene to leptin in our therapeutic armamentarium. Metabolism. 2015;64(1):1–4. doi:10.1016/j.metabol.2014.10.023
  • Brown RJ, Oral EA, Cochran E, et al. Long-term effectiveness and safety of metreleptin in the treatment of patients with generalized lipodystrophy. Endocrine. 2018;60(3):479–489. doi:10.1007/s12020-018-1589-1
  • Püschel J, Miehle K, Müller K, et al. Beneficial effects of leptin substitution on impaired eating behavior in lipodystrophy are sustained beyond 150 weeks of treatment. Cytokine. 2019;113:400–404. doi:10.1016/j.cyto.2018.10.012
  • McDuffie JR, Riggs PA, Calis KA, et al. Effects of exogenous leptin on satiety and satiation in patients with lipodystrophy and leptin insufficiency. J Clin Endocrinol Metab. 2004;89(9):4258–4263. doi:10.1210/jc.2003-031868
  • Kinzer AB, Shamburek RD, Lightbourne M, Muniyappa R, Brown RJ. Advanced lipoprotein analysis shows atherogenic lipid profile that improves after metreleptin in patients with lipodystrophy. J Endocr Soc. 2019;3(8):1503–1517. doi:10.1210/js.2019-00103
  • Chong AY, Lupsa BC, Cochran EK, Gorden P. Efficacy of leptin therapy in the different forms of human lipodystrophy. Diabetologia. 2010;53(1):27. doi:10.1007/s00125-009-1502-9
  • Oral EA, Gorden P, Cochran E, et al. Long-term effectiveness and safety of metreleptin in the treatment of patients with partial lipodystrophy. Endocrine. 2019;64(3):500–511
  • Sekizkardes H, Cochran E, Malandrino N, Garg A, Brown RJ. Efficacy of metreleptin treatment in familial partial lipodystrophy due to PPARG vs LMNA pathogenic variants. J Clin Endocrinol Metab. 2019;104(8):3068–3076. doi:10.1210/jc.2018-02787
  • Ajluni N, Dar M, Xu J, Neidert AH, Oral EA. Efficacy and safety of metreleptin in patients with partial lipodystrophy: lessons from an expanded access program. J Diabetes Metab. 2016;7(3).
  • Simha V, Subramanyam L, Szczepaniak L, et al. Comparison of efficacy and safety of leptin replacement therapy in moderately and severely hypoleptinemic patients with familial partial lipodystrophy of the Dunnigan variety. J Clin Endocrinol Metab. 2012;97(3):785–792. doi:10.1210/jc.2011-2229
  • Oral EA, Ruiz E, Andewelt A, et al. Effect of leptin replacement on pituitary hormone regulation in patients with severe lipodystrophy. J Clin Endocrinol Metab. 2002;87(7):3110–3117. doi:10.1210/jcem.87.7.8591
  • Ebihara K, Kusakabe T, Hirata M, et al. Efficacy and safety of leptin-replacement therapy and possible mechanisms of leptin actions in patients with generalized lipodystrophy. J Clin Endocrinol Metab. 2006;92(2):532–541. doi:10.1210/jc.2006-1546
  • Musso C, Cochran E, Javor E, Young J, DePaoli AM, Gorden P. The long-term effect of recombinant methionyl human leptin therapy on hyperandrogenism and menstrual function in female and pituitary function in male and female hypoleptinemic lipodystrophic patients. Metabolism. 2005;54(2):255–263. doi:10.1016/j.metabol.2004.08.021
  • Lee HL, Waldman MA, Auh S, et al. Effects of metreleptin on proteinuria in patients with lipodystrophy. J Clin Endocrinol Metab. 2019;104(9):4169–4177. doi:10.1210/jc.2019-00200
  • Vatier C, Kalbasi D, Vantyghem M-C, et al. Adherence with metreleptin therapy and health self-perception in patients with lipodystrophic syndromes. Orphanet J Rare Dis. 2019;14(1):177. doi:10.1186/s13023-019-1141-2
  • Chan JL, Koda J, Heilig JS, et al. Immunogenicity associated with metreleptin treatment in patients with obesity or lipodystrophy. Clin Endocrinol (Oxf). 2016;85(1):137–149. doi:10.1111/cen.12980
  • Aslam A, Savage DB, Coulson IH. Acquired generalized lipodystrophy associated with peripheral T cell lymphoma with cutaneous infiltration. Int J Dermatol. 2015;54(7):827–829. doi:10.1111/ijd.12185
  • Semple RK, Chatterjee VKK, O’Rahilly S. PPARγ and human metabolic disease. J Clin Invest. 2006;116(3):581–589. doi:10.1172/JCI28003
  • Barroso I, Gurnell M, Crowley VEF, et al. Dominant negative mutations in human PPARγ associated with severe insulin resistance, diabetes mellitus and hypertension. Nature. 1999;402(6764):880. doi:10.1038/47254
  • Cao H, Hegele RA. Nuclear lamin A/C R482Q mutation in Canadian kindreds with Dunnigan-type familial partial lipodystrophy. Hum Mol Genet. 2000;9(1):109–112. doi:10.1093/hmg/9.1.109
  • Eriksson M, Brown WT, Gordon LB, et al. Recurrent de novo point mutations in lamin A cause Hutchinson–Gilford progeria syndrome. Nature. 2003;423(6937):293. doi:10.1038/nature01629
  • De Sandre-giovannoli A, Bernard R, Cau P, et al. Lamin a truncation in Hutchinson-Gilford progeria. Science. 2003;300(5628):2055. doi:10.1126/science.1084125
  • Novelli G, Muchir A, Sangiuolo F, et al. Mandibuloacral dysplasia is caused by a mutation in LMNA-encoding lamin A/C. Am J Hum Genet. 2002;71(2):426–431. doi:10.1086/341908
  • Shastry S, Simha V, Godbole K, et al. A novel syndrome of mandibular hypoplasia, deafness, and progeroid features associated with lipodystrophy, undescended testes, and male hypogonadism. J Clin Endocrinol Metab. 2010;95(10):E192–E197. doi:10.1210/jc.2010-0419
  • Grahn THM, Zhang Y, Lee M-J, et al. FSP27 and PLIN1 interaction promotes the formation of large lipid droplets in human adipocytes. Biochem Biophys Res Commun. 2013;432(2):296–301. doi:10.1016/j.bbrc.2013.01.113
  • Kozusko K, Tsang VHM, Bottomley W, et al. Clinical and molecular characterization of a novel PLIN1 frameshift mutation identified in patients with familial partial lipodystrophy. Diabetes. 2015;64(1):299–310. doi:10.2337/db14-0104
  • Gandotra S, Le Dour C, Bottomley W, et al. Perilipin deficiency and autosomal dominant partial lipodystrophy. N Engl J Med. 2011;364(8):740–748. doi:10.1056/NEJMoa1007487
  • Farhan SMK, Robinson JF, McIntyre AD, et al. A novel LIPE nonsense mutation found using exome sequencing in siblings with late-onset familial partial lipodystrophy. Can J Cardiol. 2014;30(12):1649–1654. doi:10.1016/j.cjca.2014.09.007
  • Cavalcante MPV, Brunelli JB, Miranda CC, et al. CANDLE syndrome: chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature—a rare case with a novel mutation. Eur J Pediatr. 2016;175(5):735–740. doi:10.1007/s00431-015-2668-4
  • Agarwal AK, Xing C, DeMartino GN, et al. PSMB8 encoding the β5i proteasome subunit is mutated in joint contractures, muscle atrophy, microcytic anemia, and panniculitis-induced lipodystrophy syndrome. Am J Hum Genet. 2010;87(6):866–872. doi:10.1016/j.ajhg.2010.10.031
  • Donadille B, D’Anella P, Auclair M, et al. Partial lipodystrophy with severe insulin resistance and adult progeria Werner syndrome. Orphanet J Rare Dis. 2013;8(1):106. doi:10.1186/1750-1172-8-106