Clinical presentation and management of childhood lipodystrophic syndromes

Česká verzia

Authors: Lebl Jan ¹; Chiarelli Francesco ²
Authors place of work: Pediatrická klinika, 2. lékařská fakulta, Univerzita Karlova a Fakultní nemocnice v Motole, Praha ¹; Department of Paediatrics, University of Chieti, Chieti, Italy ²
Published in the journal: Čes-slov Pediat 2024; 79 (4): 221-225.
Category: Souborný referát
doi: https://doi.org/10.55095/CSPediatrie2024/036

Summary

Lipodystrophy syndromes represent a heterogeneous group of rare diseases characterized by various degree of adipose tissue loss that results in severe metabolic complications, including hypertriglyceridemia, steatohepatitis and particularly insulin resistance. These complications may increase the mortality rate. Adipokine deficiency, and especially leptin deficiency, is due to fat tissue loss. Therapy for lipodystrophy primarily consists of a conventional approach that involves standard treatments of metabolic abnormalities. Recently, recombinant leptin.(metreleptin) administration has been introduced to compensate for leptin deficiency. This therapy markedly improves the overall patients’ status and metabolic complications and was approved for the treatment of both generalized and partial lipodystrophy.

Keywords:

leptin – insulin resistance – therapy – metreleptin – lipodystrophy – metabolic complications

Zdroje

1. Lebl J, Dušátková P, Křenek Malíková J. Třicet let od objevu leptinu: poslíček tukové tkáně, regulátor jídelního chování a unikátní lék. Ces-Slov Pediat 2024; 79: 161–166.

2. Huang-Doran I, Sleigh A, Rochford JJ, et al. Lipodystrophy: metabolic insights from a rare disorder. J Endocrinol 2010; 207: 245–55.

3. Chiquette E, Oral EA, Garg A, et al. Estimating the prevalence of generalized and partial lipodystrophy: findings and challenges. Diabetes Metab Syndr Obes Targets Ther 2017; 10: 375–83.

4. Araújo-Vilar D, Santini F. Diagnosis and treatment of lipodystrophy: a step-by-step approach. J Endocrinol Invest 2019; 42: 61–7.

5. Oral EA, Simha V, Ruiz E, Andewelt A, et al. Leptin-replacement therapy for lipodystrophy. N Engl J Med 2002; 346: 570–8.

6. Mainieri F, Tagi VM, Chiarelli F. Treatment options for lipodystrophy in children. Front Endocrinol 2022; 13: 879979.

7. Garg A. Acquired and inherited lipodystrophies. N Engl J Med 2004; 350: 1220–34.

8. 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: 4500–11.

9. Zammouri J, Vatier C, Capel E, et al. Molecular and cellular bases of lipodystrophy syndromes. Front Endocrinol (Lausanne) 2022; 12: 803189.

10. Diker-Cohen T, Cochran E, Gorden P, Brown RJ. Partial and generalized lipodystrophy: comparison of baseline characteristics and response to metreleptin. J Clin Endocrinol Metab 2015; 100: 1802–10.

11. Garg A. Clinical review. Lipodystrophies: genetic and acquired body fat disorders. J Clin Endocr Metab 2011; 96: 3313–25.

12. Oral EA. Lipoatrophic diabetes and other related syndromes. Rev Endocr Metab Disord 2003; 4: 61–77.

13. Handelsman Y, Oral EA, Bloomgarden ZT, et al. The clinical approach to the detection of lipodystrophy - an AACE consensus statement. Endocr Pract 2013; 19: 107–16.

14. Moon HS, Dalamaga M, Kim SY, et al. Leptin’s role in lipodystrophic and nonlipodystrophic insulin-resistant and diabetic individuals. Endocr Rev 2013; 34: 377–412.

15. Papendieck L, Araujo MB. Clinical outcome in a series of pediatric patients With congenital generalized lipodystrophies treated with dietary therapy. J Pediatr Endocrinol Metab 2018; 31: 77–83.

16. Foss-Freitas MC, Akinci B, Luo Y, et al. Diagnostic strategies and clinical management of lipodystrophy. Expert Rev Endocrinol Metab 2020; 15: 95–114.

17. Manlhiot C, Larsson P, Gurofsky RC, et al. Spectrum and management of hypertriglyceridemia among children in clinical practice. Pediatrics 2009; 123: 458–65.

18. Polyzos SA, Perakakis N, Mantzoros CS. Fatty liver in lipodystrophy: A review with a focus on therapeutic perspectives of adiponectin and/or leptin replacement. Metab Clin Exp 2019; 96: 66–82.

19. Ahmad Z, Subramanyam L, Szczepaniak L, et al. cholic acid for hepatic steatosis in patients with lipodystrophy: A randomized, controlled trial. Eur J Endocrinol 2013; 168: 771–8.

20. Cochran E, Musso C, Gorden P. The use of U-500 in patients with extreme insulin resistance. Diabetes Care 2005; 28: 1240–4.

21. Kawana Y, Imai J, Sawada S, et al. Sodium-glucose cotransporter 2 inhibitor improves complications of lipodystrophy: A case report. Ann Intern Med 2017; 166: 450–51.

22. Meehan CA, Cochran E, Kassai A, et al. Metreleptin for injection to treat the complications of leptin deficiency in patients with congenital or acquired generalized lipodystrophy. Expert Rev Clin Pharmacol 2016; 9: 59–
68.

23. Özen S, Akıncı B, Oral EA. Current diagnosis, treatment and clinical challenges in the management of lipodystrophy syndromes in children and young people. J Clin Res Pediatr Endocrinol 2020; 12: 17–28.

24. Bellini E, Grieco MP, Raposio E. A Journey through liposuction and liposculture: Review. Ann Med Surg 2017; 24: 53–60.

25. Akinci B, Sahinoz M, Oral E. Lipodystrophy syndromes: Presentation and treatment. Feingold KR, Anawalt B, Boyce A, eds. South Dartmouth, MA: MDText.com, Inc. 2000.

26. Dayan SH, Humphrey S, Jones DH, et al. Overview of ATX-101.(deoxycholic acid injection): A nonsurgical approach for reduction of submental fat. Dermatol Surg 2016; 42 (Suppl 1): S263–70.

27. Tanaka T, Kusakabe T, Ebihara K, et al. Practice guideline for lipodystrophy syndromes— clinically important diseases of the Japan Endocrine Society (JES) Endocr J 2021; 68: 1027–42.

28. Considine RV, Sinha MK, Heiman ML, et al. Serum immunoreactive leptin concentrations in normal-weight and obese humans. N Engl J Med 1996; 334: 292–5.

29. Blüher S, Mantzoros CS. Leptin in humans: Lessons from translational research. Am J Clin Nutr 2009; 89: 991S–997S.

30. Muoio DM, Dohm GL. Peripheral metabolic actions of leptin. Best Pract Res Clin Endocrinol Metab 2002; 16: 653–66.

31. Quaye E, Chacko S, Startzell M, Brown RJ. Leptin decreases gluconeogenesis and gluconeogenic substrate availability in patients with lipodystrophy. J Clin Endocrinol Metab 2024; 109: e209–14.

32. Triantafyllou GA, Paschou SA, Mantzoros CS. Leptin and hormones: Energy homeostasis. Endocrinol Metab Clin North Am 2016; 45: 633–45.

33. Meek TH, Morton GJ. The role of leptin in diabetes: Metabolic effects. Diabetologia 2016; 59: 928–32.

34. Akinci B, Onay H, Demir T, et al. Natural history of congenital generalized lipodystrophy: A nationwide study from Turkey. J Clin Endocrinol Metab 2016; 101: 2759–67.

35. Gupta N, Asi N, Farah W, et al. Clinical features and management of non-HIV-related lipodystrophy in children: A systematic review. J Clin Endocrinol Metab 2017; 102: 363–74.

36. Savage DB. Mouse models of inherited lipodystrophy. Dis Model Mech 2009; 2: 554–62.

37. Moitra J, Mason MM, Olive M, et al. Life without white fat: A transgenic mouse. Genes Dev 1998; 12: 3168–81.

38. Gavrilova O, Marcus-Samuels B, Graham D, et al. Surgical implantation of adipose tissue reverses diabetes in lipoatrophic mice. J Clin Invest 2000; 105: 271–8.

39. Shimomura I, Hammer RE, Ikemoto S, et al. Leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy. Nature 1999; 401(6748): 73–6.

40. Tchang BG, Shukla AP, Aronne LJ. Metreleptin and generalized lipodystrophy and evolving therapeutic perspectives. Expert Opin Biol Ther 2015; 15: 1061–75.

41. Myalepta: Summaries of Product Characteristics (SPC) 2020.