Preview

Федеральные клинические рекомендации по диагностике, лечению и ведению детей и подростков с врожденным гиперинсулинизмом

https://doi.org/10.14341/probl201460231-41

Полный текст:

Аннотация

Врожденный гиперинсулинизм (ВГИ) - это наследственное заболевание, характеризующееся неадекватной гиперсекрецией инсулина бета-клетками поджелудочной железы, что приводит к развитию гипогликемий. При отсутствии лечения, гипогликемии в детском возрасте могут приводить к развитию судорог и тяжелым неврологическим осложнениям. Ранняя диагностика и своевременное начало адекватной терапии необходимы для предотвращения поражения ЦНС. ВГИ является гетерогенным заболеванием, как этилогически, так и с точки зрения клинического течения и разнообразия морфологических форм. В настоящий момент в литературе описано 9 генов, мутации которых могут приводить к развитию ВГИ. Помимо этого, существуют синдромальные патологии, в симптомокомплекс которых может входить гиперинсулинемические гипогликемии. В данном обзоре литературы нами представлены основные принципы класиификации ВГИ, описана клиническая вариабельность течения заболевания, а также даны рекомендации по диагностике и подходам к лечению различных форм ВГИ.

Об авторе

М А Меликян
ФГБУ «Эндокринологический научный центр» Минздрава России, Москва


Список литературы

1. Glaser B, Thornton PS, Otonkoski T, Junien C. The genetics of neonatal hyperinsulinism. Arch Dis Child 2000; 82: 79-86.

2. Меликян М.А., Карева М.А., Петряйкина Е.Е., Волков И.Э., Аверьянова Ю.В., Коломина И.Г., и др. Врожденный гиперинсулинизм. Результаты молекулярно-генетических исследований в российской популяции. // Проблемы эндокринологии. - 2012. - Т. 58. - №2 - С. 3-9. doi: 10.14341/probl20125823-9

3. Aynsley-Green A, Hussain K, Hall J et al. Practical management of hyperinsulinism in infancy. Arch Dis Child Fetal Neonatal Ed 2000; 82: 98-107.

4. Wolfsdorf JI, Weinstein DA. Hypoglycemia in Children. Ed. 5-th. Pediatr Endocrinol 2007; 1: 291-327.

5. Thomas PM, Cote GJ, Wohilk N et al. Mutations in the sulphonylurea receptor and familial persistent hyperinsulinemic hypoglycemia of infancy. Science 1995; 268: 426-429.

6. Thomas PM, Yuyang Y, Lightner E. Mutation of the pancreatic islet inward rectifier, Kir6.2 also leads to familial persistent hyperinsulinemic hypoglycemia of infancy. Hum Mol Genet 1996; 5(11): 1809-1812.

7. Nestorowicz A, Inagaki N, Gonoi T, Schoor KP, Wilson BA, Glaser B, et al.

8. A nonsense mutation in the inward rectifier potassium channel gene, Kir6.2, is associated with familial hyperinsulinism. Diabetes 1997; 46: 1743-1748.

9. Dunne MJ, Kane C, Shepherd RM, Sanchez JA, James RF, Johnson PR, et al. Familial persistent hyperinsulinemic hypoglycemia of infancy and mutations in the sulfonylurea receptor. N Engl J Med 1997; 336: 703-706.

10. Cartier EA, Conti LR, Vandenberg CA, Shyng SL. Defective trafficking and function of KATP channels caused by a sulfonylurea receptor 1 mutation associated with persistent hyperinsulinemic hypoglycemia of infancy. Proc Natl Acad Sci USA 2001; 98:2882-2887.

11. Crane A, Aguilar-Bryan L. Assembly, maturation, and turnover of K(ATP) channel subunits. J Biol Chem 2004; 279: 9080-9090.

12. Yan F, Lin CW, Weisiger E, Cartier EA, Taschenberger G, Shyng SL. Sulfonylureas correct trafficking defects of ATP-sensitive potassium channels caused by mutations in the sulfonylurea receptor. J Biol Chem 2004; 279: 11096-11105.

13. Flanagan SE, Clauin S, Bellanne-Chantelot C, de Lonlay P, Harries LW, Gloyn AL, Ellard S. Update of mutations in the genes en- coding the pancreatic beta-cell K(ATP) channel subunits Kir6.2 (KCNJ11) and sulfonylurea receptor 1 (ABCC8) in diabetes mellitus and hyperinsulinism. Hum Mutat 2009; 30: 170-180.

14. James C, Kapoor RR, Ismail D. The genetic basis of congenital hyperinsulinism. J Med Genet 2009; 46: 289-299.

15. Stanley CA, Lieu YK, Hsu BY et al. Hyperinsulinism and hyperammonemia in infants with regulatory mutations of the glutamate dehydrogenase gene. N Engl J Med 1998; 338: 1352-1357.

16. Christesen HB, Tribble ND, Molven A, Siddiqui J, Sandal T, Brusgaard K, Ellard S, Njølstad PR, Alm J, Brock Jacobsen B, Hussain K, Gloyn AL. Activating glucokinase (GCK) mutations as a cause of medically responsive congenital hyperinsulinism: prevalence in children and characterisation of a novel GCK mutation. Eur J En- docrinol 2008; 159: 27-34.

17. Cuesta-Munoz AL, Huopio H, Otonkoski T, Gomez-Zumaquero JM, Nanto-Salonen K, Rahier J, Lopez-Enriquez S, Garcia-Gimeno MA, Sanz P, Soriguer FC, Laakso M. Severe Persistent Hyperinsulinemic Hypoglycemia due to a De Novo Glucokinase Mutation. Diabetes 2004; 53: 2164-2168.

18. Sayed S, Langdon DR, Odili S et al. Extremes of clinical and enzymatic phenotypes in children with hyperinsulinism caused by glucokinase activating mutations. Diabetes 2009; 58: 1419-1427.

19. Bhandari K, Rodríguez-Bada, Heyman M, García-Gimeno, Cobo Vuilleumier, Sanz, et al. Large Islets, Beta-Cell Proliferation, and a Glucokinase Muta- tion. N Engl J Med 2010; 363: 2178.

20. Christesen HB, Jacobsen BB, Odili S, Buettger C, Cuesta-Munoz A, Hansen T, Brusgaard K, Massa O, Magnuson MA, Shiota C, Matschinsky FM, Barbetti F. The second activating glucokinase mutation (A456V): implications for glucose homeostasis and diabetes therapy. Diabetes 2002; 51: 1240-1246.

21. Gloyn AL, Noordam K, Willemsen MA, Ellard S, Lam WW, Campbell IW, Midgley P, Shiota C, Buettger C, Magnuson MA, Matschin- sky FM, Hattersley AT. Insights into the biochemical and genetic basis of glucokinase activation from naturally occurring hypoglycemia mutations. Diabetes 2003; 52: 2433-2440.

22. Wabitsch M, Lahr G, Van de Bunt M, Marchant C, Lindner M, von Puttkamer J, Fenneberg A, Debatin KM, Klein R, Ellard S, Clark A, Gloyn AL. Heterogeneity in disease severity in a family with a novel G68V GCK activating mutation causing persistent hyperinsulinaemic hypoglycaemia of infancy. Diabet Med 2007; 24: 1393-1399.

23. Baretti F, Cobo-Vuilleumier N, Dionisi-Vici C, Toni S, Ciampalini P, Massa O, et al. Opposite Clinical Phenotypes of Glucokinase Disease: Description of a Novel Activating Mutation and Contiguous Inactivating Mutations in Human Glucokinase (GCK) Gene. Mol Endocrinol 2009; 23: 1983-1989.

24. Beer NL, van de Bunt M, Colclough K, Lukacs Ch, Arundel P, Chik C, Grimsby J, Ellard S, Gloyn AL. Discovery of a Novel Site Regulating Glucokinase Activity following Characterization of a New Mutation Causing Hyperinsulinemic Hypoglycemia in Humans. J Biol Chem 2011; 21: 19118-19126.

25. Hussain K, Clayton PT, Krywawych S, Chatziandreou I, Mills P, Ginbey DW, Geboers AJ, Berger R, van den Berg IE, Eaton S. Hyperinsulinism of infancy associated with a novel splice site mutation in the SCHAD gene. J Pediatr 2005; 146: 706-708.

26. Pearson ER, Boj SF, Steele AM, Barrett T, Stals K, Shield JP, Ellard S, Ferrer J, Hattersley AT. Macrosomia and hyperinsulinaemic hypoglycaemia in patients with heterozygous mutations in the HNF4A gene. PLoS Med 2007; 4(4): e118.

27. Gonza´lez-Barroso MM, Giurgea I, Bouillaud F, Anedda A, Bellanne-Chantelot C et al. Mutations in UCP2 in Congenital Hyperinsulinism Reveal a Role for Regulation of Insulin Secretion. PLoS ONE 2008; 3(12): e3850. doi:10.1371/journal.pone.0003850

28. Rahier J, Guiot Y, Sempoux C. Persistent hyperinsulinaemic hypoglycaemia of infancy: a heterogeneous syndrome unrelated to nesidioblastosis. Arch Dis Child Fetal Neonatal Ed 2000; 82: F108-F112.

29. Kapoor RR, Flanagan SE, James C, Shield J, Ellard S, Hussain K. Hyperinsulinaemic hypoglycaemia Arch Dis Child 2009; 94: 450-457.

30. Palladino AA, Bennett MJ, Stanley CA. Hyperinsulinism in infancy and childhood: when an insulin level is not always enough. Ann Biol Clin (Paris) 2009; 67(3): 245-254.

31. de Lonlay P, Fournet JC, Touati G et al. Heterogeneity of persistent hyperinsulinaemic hypoglycaemia. A series of 175 cases. Eur J Pediatr 2002; 161: 37-48.

32. Kapoor RR, James C, Hussain K. Advances in the diagnosis and management of hyperinsulinemic hypoglycemia. Nat Clin Pract Endocrinol Metabol 2009; 5(2): 101-112.

33. Hussain K, Hindmarsh P, Aynsley-Gree. Neonates with symptomatic hyperinsulinemic hypoglycemia generate inappropriately low serum cortisol counterregulatory hormonal responses. J Clin Endocrinol Metabol 2003; 88(9): 4342-4347.

34. Davis MR, Shamoon H. Counter-regulatory adaptation to recurrent hypoglycaemia in normal humans. J Clin Endocrinol Metab 1991; 73: 995-1000.

35. Brun JF, Fedou C, Mercier J. Postprandial reactive hypoglycemia. Diabet Metabol 2000; 26(5): 337-351.

36. Otonkoski T, Jiao H, Kaminen-Ahola N et al. Physical exerciseinduced hypoglycemia caused by failed silencing of monocarboxylate transporter 1 in pancreatic Beta cells. Am J Hum Genet 2007;81: 467-474.

37. Rahier J, Guiot Y, Sempoux C. Morphologic analysis of focal and diffuse forms of congenital hyperinsulinism. Semin Pediatr Surg 2011; 20(1): 3-12.

38. Ryan F, Devaney D, Joyce C, Nestorowicz A, Permutt MA, Glaser B, Barton DE, Thornton PS. Hyperinsulinism: molecular aetiology of focal disease. Arch Dis Child 1998; 79: 445-447.

39. de Lonlay P, Simon-Carre A, Ribeiro MJ et al. Congenital hyperinsulinism: pancreatic [18F]fluoro-L-dihydroxyphenylalanine (DOPA) positron emission tomography and immunohistochem- istry study of DOPA decarboxylase and insulin secretion. J Clin Endocrinol Metabol 2006; 91: 933-940.

40. Mohnike K, Blankenstein O, Minn H et al. [F]-DOPA positron emission tomography for preoperative localization in congenital hyperinsulinism. Horm Res 2008; 70: 65-72.

41. Hardy OT, Hernandez-Pampaloni M, Saffer JR et al. Accuracy of [18F]fluorodopa positron emission tomography for diagnosing and localizing focal congenital hyperinsulinism. J Clin Endo- crinol Metabol 2007; 92: 4706-4711.

42. Hussain K, Blankenstein O, De Lonlay P, Christesen HT. Hyperinsulinaemic hypoglycaemia: biochemical basis and the importance of maintaining normoglycaemia during management. Arch Dis Child 2007; 92: 568-570.

43. Meissner T, Wendel U, Burgard P, Schaetzle S, Mayatepek E. Long-term follow-up of 114 patients with congenital hyperinsulinism. European journal of endocrinology. Eur Federat Endocr Soc 2003;149(1):43-51.

44. Filan PM, Inder TE, Cameron FJ, Kean MJ, Hunt RW. Neona- tal hypoglycemia and occipital cerebral injury. J Paediatr 2006; 148(4): 552-555.

45. Fe´ke´te´ CN, de Lonlay P, Jaubert F, Rahier J, Brunelle F, Saudubray JM. The surgical management of congenital hyperinsulinemic hypoglycemia in infancy. J Pediatr Surg 2004; 39(3): 267-269.

46. Mercimek-Mahmutoglu S, Rami B, Feucht M, Herle M, Rittinger O, Stoeckler-Ipsiroglu S, Schober E. Long-term follow-up of patients with congenital hyperinsulinism in Austria. J Pediatr Endocrinol Metabol 2008; 21(6): 523-532.


Для цитирования:


Меликян М.А. Федеральные клинические рекомендации по диагностике, лечению и ведению детей и подростков с врожденным гиперинсулинизмом. Проблемы Эндокринологии. 2014;60(2):31-41. https://doi.org/10.14341/probl201460231-41

For citation:


Melikyan M.A. Federal clinical practice guidelines on the diagnostics, treatment, and management of the children and adolescents presenting with congenital hyperinsulinism. Problems of Endocrinology. 2014;60(2):31-41. (In Russ.) https://doi.org/10.14341/probl201460231-41

Просмотров: 80


Creative Commons License
Контент доступен под лицензией Creative Commons Attribution 4.0 License.


ISSN 0375-9660 (Print)
ISSN 2308-1430 (Online)