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Федеральное государственное бюджетное учреждение науки
"Институт токсикологии Федерального медико-биологического агентства"

Институт теоретической и экспериментальной биофизики Российской академии наук.


Адрес редакции и реквизиты

199406, Санкт-Петербург, ул.Гаванская, д. 49, корп.2

ISSN 1999-6314

Российская поисковая система

Vol. 20, Art. 32 (pp. 385-403)    |    2019       

Congenital hyperinsulinism: etiopathogenesis and treatment (review)
Perminova A.A.

Federal State Budgetary Institution "Almazov National Medical Research Centre" of the Ministry of Health of the Russian Federation

Brief summary

Congenital hyperinsulinism is one of the most common causes of hypoglycemia in infants. Because of absence of adequate pharmacological correction of hypoglycemic attacks, the development of irreversible changes in the central nervous system with the subsequent disability of such patients is possible. Due to the ineffectiveness of conservative therapy, in many cases surgical intervention is required. The review was compiled in order to combine the available data in the English literature on congenital hyperinsulinism, which, despite their fewness, are extremely fragmented. This review presents data on the etiology, pathogenesis, and diagnostic methods of congenital hyperinsulinism, as well as the possibilities for its medical correction. In particular, various mutations and pathogenetic mechanisms, possibilities and difficulties of preoperative and intraoperative diagnostics, tactics and possibilities of drug therapy of congenital hyperinsulinism are described.

Key words

congenital hyperinsulinism, hyperinsulinism, nesidioblastosis, hyperinsulinaemic hypoglycaemia, pancreatic islets.

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Reference list

1. De León D.D., Stanley C.A. Mechanisms of disease: advances in diagnosis and treatment of hyperinsulinism in neonates. Nat Clin Pract Endocrinol Metab. 2007; 3: 57-68.

2. Laidlaw G.F. Neisidioblastoma, the islet tumour of pancreas. Am J Pathol. 1938; 14:125-139.

3. Stanley C.A. Advances in diagnosis and treatment of hyperinsulinism in infants and children. J Clin Endocrinol Metab. 2002; 87: 4857-9.

4. James C, Kapoor RR, Ismail D, et al. The genetic basis of congenital hyperinsulinism. J Med Genet 2009;46(5):289-99.

5. Arnoux J.B., Verkarre V., Saint-Martin C. et al. Congenital hyperinsulinism: current trends in diagnosis and therapy. Orphanet J Rare Dis. 2011;6:63.

6. Lord K., De León, D.D. Hyperinsulinism in the neonate. Clinics in Perinatology, 2018; 45(1): 61-74. doi:10.1016/j.clp.2017.10.007

7. McQuarrie I. Idiopathic spontaneously occurring hypoglycemia in infants Clinical Significance of Problem and Treatment. Archives of Pediatrics & Adolescent Medicine. 1954; 87(4): 399-428. doi:10.1001/archpedi.1954.02050090387001

8. Galcheva S., Demirbilek H., Al-Khawaga S. and Hussain K. The genetic and molecular mechanisms of congenital hyperinsulinism. Front. Endocrinol. 2019; 10: 111.

9. Fu Z., Gilbert E.R., Liu D. Regulation of insulin synthesis and secretion and pancreatic Beta-cell dysfunction in diabetes. Curr Diabetes Rev. 2013;9(1):25-53.

10. Thomas P., Ye 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):1809-12.

11. Thomas P.M., Cote G.J., Wohllk N. et al. Mutations in the sulfonylurea receptor gene in familial persistent hyperinsulinemic hypoglycemia of infancy. Science. 1995; 268(5209):426-9.

12. Verkarre V., Fournet J.C., De Lonlay P. et al. Paternal mutation of the sulfonylurea receptor (SUR1) gene and maternal loss of 11p15 imprinted genes lead to persistent hyperinsulinism in focal adenomatous hyperplasia. J Clin Invest. 1998;102(7): 1286-91.

13. Snider K.E., Becker S., Boyajian L. et al. Genotype and phenotype correlations in 417 children with congenital hyperinsulinism. J Clin Endocrinol Metab 2013; 98(2):E355-63.

14. Damaj L., le Lorch M., Verkarre V., Werl C. et al. Chromosome 11p15 paternal isodisomy in focal forms of neonatal hyperinsulinism. J Clin Endocrinol Metab. 2008; 93:4941-47. doi: 10.1210/jc.2008-0673

15. Torekov S.S., Iepsen E., Christiansen M., Linneberg A. et al. KCNQ1 long QT syndrome patients have hyperinsulinemia and symptomatic hypoglycemia. Diabetes. 2014; 63:1315-25. doi: 10.2337/db13-1454

16. Scholl U.I., Goh G., Stolting G., de Oliveira R.C. et al. Somatic and germline CACNA1D calcium channel mutations in aldosterone-producing adenomas and primary aldosteronism. Nat Genet. 2013; 45:1050-54. doi: 10.1038/ng.2695

17. Flanagan S.E., Franco E., Allen H.L., Zerah M. et al. Analysis of transcription factors key for mouse pancreatic development establishes NKX2-2 and MNX1 mutations as causes of neonatal diabetes in man. Cell Metabolism. 2014; 19: 146-154.

18. Otonkoski T., Kaminen N., Ustinov J., Lapatto R. et al. Physical exercise-induced hyperinsulinemic hypoglycemia is an autosomal-dominant trait characterized by abnormal pyruvate-induced insulin release. Diabetes. 2003;52:199-204. doi: 10.2337/diabetes.52.1.199

19. Stanley C.A. Hyperinsulinism/hyperammonemia syndrome: insights into the regulatory role of glutamate dehydrogenase in ammonia metabolism. Mol Genet Metab. 2004; 81:45-51. doi: 10.1016/j.ymgme.2003.10.013

20. Bahi-Buisson N., Roze E., Dionisi C. et al. Neurological aspects of hyperinsulinismhyperammonaemia syndrome. Dev Med Child Neurol 2008;50(12):945-9.

21. Heslegrave A.J., Hussain K. Novel insights into fatty acid oxidation, amino acid metabolism, and insulin secretion from studying patients with loss of function mutations in 3-hydroxyacyl-CoA dehydrogenase. J Clin Endocrinol Metab. 2013; 98:496-501. doi: 10.1210/jc.2012-3134

22. Ferrara C.T., Boodhansingh K.E., Paradies E., Giuseppe F. et al. Novel hypoglycemia phenotype in congenital hyperinsulinism due to dominant mutations of Uncoupling Protein 2 (UCP2). J Clin Endocrinol Metab. 2017; 102:942-49. doi: 10.1210/jc.2016-3164

23. Henquin J.C., Sempoux C., Marchandise J., Godecharles S. et al. Congenital hyperinsulinism caused by hexokinase I expression or glucokinase-activating mutation in a subset of beta-cells. Diabetes. 2013;62:1689-96. doi: 10.2337/db12-1414

24. Cabezas O.R., Flanagan S.E., Stanescu H., García-Martínez E. et al. Polycystic kidney disease with hyperinsulinemic hypoglycemia caused by a promoter mutation in phosphomannomutase 2. J Am Soc Nephrol. 2017; 28:2529-39. doi: 10.1681/ASN.2016121312

25. Kapoor R.R., Locke J., Colclough K. et al. Persistent hyperinsulinemic hypoglycemia and maturity-onset diabetes of the young due to heterozygous HNF4A mutations. Diabetes 2008;57(6):1659-63.

26. Vajravelu M.E., Chai J., Krock B., Baker S. et al. Congenital hyperinsulinism and hypopituitarism attributable to a novel mutation in FOXA2. J Clin Endocrinol Metab. 2018; 103:1042-47. doi: 10.1210/jc.2017-02157

27. Sempoux C., Capito C, Bellanne´-Chantelot C., Verkarre V. et al. Morphological mosaicism of the pancreatic islets: a novel anatomopathological form of persistent hyperinsulinemic hypoglycemia of infancy. J Clin Endocrinol Metab. 2011; 96(12): 3785-3793. doi: 10.1210/jc.2010-3032

28. Houghton J., Banerjee I., Shaikh G., Jabbar Sh. et al. Unravelling the genetic causes of mosaic islet morphology in congenital hyperinsulinism. J Pathol Clin Res. 2019; published online in Wiley Online Library (wileyonlinelibrary.com). Doi: 10.1002/cjp2.144

29. Kellaway S.G., Mosinska K., Mohamed Z., Ryan A. et al. Increased proliferation and altered cell cycle regulation in pancreatic stem cells derived from patients with congenital hyperinsulinism. PloS ONE. 2019;14(9): e0222350. doi: 10.1371/journal.pone.0222350

30. Darrow D.C. Mental deterioration associated with convulsions and hypoglycemia. Am. J. Dis. Child. 1936; 51:575.

31. Sousa-Santos F., Simões H., Castro-Feijóo L., Rodríguez P.C., et al. Congenital hyperinsulinism in two siblings with ABCC8 mutation: same genotype, different phenotypes. Archives of Endocrinology and Metabolism. 2018;62(5): 560-565. doi:10.20945/2359-3997000000077

32. Ferrara C., Patel P., Becker S., Stanley C.A. Et al. (2016). Biomarkers of insulin for the diagnosis of hyperinsulinemic hypoglycemia in infants and children. The Journal of Pediatrics. 2016;168:212-219. doi:10.1016/j.jpeds.2015.09.045

33. Borelli M.I., Villar M.J., Orezzoli A., Gagliardino J.J. Presence of DOPA decarboxylase and its localisation in adult rat pancreatic islet cells. Diabetes Metab. 1997;23:161-163.

34. Hussain K., Seppänen M., Näntö-Salonen K., Adzick N.S. Et al. The diagnosis of ectopic focal hyperinsulinism of infancy with [18F]-dopa positron emission tomography. J Clin Endocrinol Metab. 2006; 91:2839-2842.

35. Christiansen C.D., Petersen H., Nielsen A.L., Detlefsen S. et al.18F-DOPA PET/CT and 68Ga-DOTANOC PET/CT scans as diagnostic tools in focal congenital hyperinsulinism: a blinded evaluation. European Journal of Nuclear Medicine and Molecular Imaging. 2017; 45(2): 250-261.

36. Jodal A., Schibli R., Béhé M. Targets and probes for non-invasive imaging of β-cells. Eur J Nucl Med Mol Imaging 2017; 44:712-727. doi: 10.1007/s00259-016-3592-1

37. Han B., Mohamed Z., Estebanez M.S., Craigie R.J. et al. Atypical forms of congenital hyperinsulinism in infancy are associated with mosaic patterns of immature islet cells. J Clin Endocrinol Metab. 2017; 102(9): 3261-3267.

38. Craigie R.J., Salomon-Estebanez M., Yau D., Han B. et al. Clinical diversity in focal congenital hyperinsulinism in infancy correlates with histological heterogeneity of islet cell lesions. Front. Endocrinol. 2018; 9: 619.

39. Sempoux Ch., Guiot Y., Jaubert F., Rahier J. Focal and diffuse forms of congenital hyperinsulinism: the keys for differential diagnosis. Endocrine Pathology. 2004; 15(3): 241-246.

40. Han B., Newbould M., Batra G., Cheesman E. et al. Enhanced islet cell nucleomegaly defines diffuse congenital hyperinsulinism in infancy but not other forms of the disease. Am J Clin Pathol. 2016; 145: 757-768.

41. Arya V., Mohammed Z., Blankenstein O., De Lonlay P,. Hussain K. Hyperinsulinaemic hypoglycaemia. Horm Metab Res. 2014; 46 (3):157-70.

42. Young F.G.: Diabetogenic action of crude anterior pituitary extracts. Biochem. J. 1938; 32(3):513-523.

43. Talbot N.B.; Crawford J.D., Bailey C.C. Use of mesoxalyl urea (alloxan) in treatment of an infant with convulsions due to idiopathic hypoglycemia. Pediatrics. 1948; 1(3):337-45.

44. Braun M. et al. Somatostatin release, electrical activity, membrane currents and exocytosis in human pancreatic delta cells. Diabetologia. 2009;52:1566-78.

45. Gillis D. Familial Hyperinsulinism. 2003 Aug 19 [Updated 2019 Mar 21]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews? [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020.

46. Mohnike K., Blankenstein O., Pfuetzner A., Pötzsch S. et al. Long-term non-surgical therapy of severe persistent congenital hyperinsulinism with glucagon. Horm Res. 2008; 70:59-64.

47. Guemes M., Shah P., Silvera S. et al. Assessment of nifedipine therapy in hyperinsulinemic hypoglycemia due to mutations in the ABCC8 gene. J Clin Endocrinol Metab 2017;102(3):822-30.

48. Cosio A.P., Thornton P. Current and emerging agents for the treatment of hypoglycemia in patients with congenital hyperinsulinism. Pediatric Drugs.2019; 21:123-136. doi: 10.1007/s40272-019-00334-w

49. Calabria A.C., Li C., Gallagher P.R. et al. GLP-1 receptor antagonist exendin-(9-39) elevates fasting blood glucose levels in congenital hyperinsulinism owing to inactivating mutations in the ATP-sensitive K+ channel. Diabetes. 2012;61:2585-2591.

50. Graham E.A., Hartmann A.F. Subtotal resection of pancreas for hypoglycemia. Surg., Gynec. & Obst. 1934;59:474.

51. Lord K., Radcliffe J., Gallagher P.R. et al. High risk of diabetes and neurobehavioral deficits in individuals with surgically treated hyperinsulinism. J Clin Endocrinol Metab 2015;100(11):4133-9.

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