Vnitr Lek 2016, 62(Suppl 4):103-112

Actual trends in diagnostics and treatment of congenital hyperinsulinism

Juraj Staník1,2, Martina Škopková1, Monika Rosoľanková3, Iwar Klimeš1, Daniela Gašperíková1,*
1 DIABGENE & Laboratórium diabetu a porúch metabolizmu, Ústav experimentálnej endokrinológie, Biomedicínske centrum SAV, Bratislava, Slovenská republika
2 I. detská klinika LF UK a DFNsP, Bratislava, Slovenská republika
3 Neonatologická klinika intenzívnej medicíny LF UK a DFNsP Bratislava, Slovenská republika

Congenital hyperinsulinism (CHI) is the most common cause of severe persistent hypoglycemia in neonates and infants. Early diagnosis and effective treatment (based on the principles of pharmacogenetics) play the key role for the prognosis. The DNA anlysis, which can identify mutation in one of the 11 genes causing MODY, is crutial in the diagnostics. Moreover, The genotype determines also the optimal therapy approach (medicaments, diet or rarely surgery). There was a large progress of novel medicaments treating particularly most severe (diazoxide-resistant) forms of CHI.

Keywords: congenital hyperinsulinism; diazoxid; DNA analysis; hypoglycemia; somatostatine analogues

Received: September 3, 2016; Accepted: November 4, 2016; Published: August 1, 2016  Show citation

ACS AIP APA ASA Harvard Chicago Chicago Notes IEEE ISO690 MLA NLM Turabian Vancouver
Staník J, Škopková M, Rosoľanková M, Klimeš I, Gašperíková D. Actual trends in diagnostics and treatment of congenital hyperinsulinism. Vnitr Lek. 2016;62(Supplementum 4):103-112.
Share...
Download citation
  • BibTeX (.bib)
  • Bookends (.ris)
  • EasyBib (.ris)
  • EndNote (.enw)
  • EndNote 8 (.xml)
  • ISI WoS (.isi)
  • Medlars (.medlars)
  • Mendeley (.ris)
  • MODS (.xml)
  • Papers (.ris)
  • RefWorks (.txt)
  • RefManager (.ris)
  • RIS (.ris)
  • MS Word (.xml)
  • Zotero (.ris)
    • Open full article

    References

    1. Stanik J, Huckova M, Stanikova D et al. Genetics of monogenic forms of diabetes. Vnitř Lék 2011; 57(11): 937-945. Go to PubMed...
    2. Lang TF, Hussain K. Pediatric hypoglycemia. Adv Clin Chem 2014; 63: 211-245. Go to original source... Go to PubMed...
    3. Palladino AA, Bennett MJ, Stanley CA. Hyperinsulinism in infancy and childhood: when an insulin level is not always enough. Clin Chem 2008; 54(2): 256-263. Go to original source... Go to PubMed...
    4. Mathew PM, Young JM, Abu-Osba YK et al. Persistent neonatal hyperinsulinism. Clin Pediatr (Phila) 1988; 27(3): 148-151. Go to original source... Go to PubMed...
    5. Glaser B, Blech I, Krakinovsky Y et al. ABCC8 mutation allele frequency in the Ashkenazi Jewish population and risk of focal hyperinsulinemic hypoglycemia. Genet Med 2011; 13(10): 891-894. Dostupné z DOI: <http://dx.doi.org/10.1097/GIM.0b013e31821fea33>. Go to original source... Go to PubMed...
    6. Flanagan SE, Kapoor RR, Hussain K. Genetics of congenital hyperinsulinemic hypoglycemia. Semin Pediatr Surg 2011; 20(1): 13-17. Dostupné z DOI: <http://dx.doi.org/10.1053/j.sempedsurg.2010.10.004> Go to original source... Go to PubMed...
    7. Senniappan S, Shanti B, James C et al. Hyperinsulinaemic hypoglycaemia: genetic mechanisms, diagnosis and management. J Inherit Metab Dis 2012; 35: 589-601. Go to original source... Go to PubMed...
    8. Dunne MJ, Cosgrove KE, Shepherd RM et al. Hyperinsulinism in infancy: from basic science to clinical disease. Physiol Rev 2004; 84(1): 239-275. Go to original source... Go to PubMed...
    9. Arnoux JB, Verkarre V, Saint-Martin C et al. Congenital hyperinsulinism: current trends in diagnosis and therapy. Orphanet J Rare Dis 2011; 6: 63. Dostupné z DOI: <http://dx.doi.org/10.1186/1750-1172-6-63> Go to original source... Go to PubMed...
    10. Arnoux JB, de Lonlay P, Ribeiro MJ et al. Congenital hyperinsulinism. Early Hum Dev 2010; 86(5): 287-294. Dostupné z DOI: <http://dx.doi.org/10.1016/j.earlhumdev.2010.05.003>. Go to original source... Go to PubMed...
    11. Akcay T, Taskin N, Ulucan K et al. Congenital hyperinsulinism and cardiomyopathy. Fetal Pediatr Pathol 2012; 31(3): 190. Dostupné z DOI: <http://dx.doi.org/10.3109/15513815.2012.656831>. Go to original source... Go to PubMed...
    12. Bulbul A, Bolat F, Comert S et al. Persistent hyperinsulinemic hypoglycemia with left ventricular hypertrophy and dysrhythmia: a case report. Fetal Pediatr Pathol 2010; 29(3): 165-171. Dostupné z DOI: <http://dx.doi.org/10.3109/15513811003777334>. Go to original source... Go to PubMed...
    13. Aynsley-Green A, Hussain K, Hall J et al. Practical management of hyperinsulinism in infancy. Arch Dis Child Fetal Neonatal Ed 2000; 82(2): F98-F107. Go to original source... Go to PubMed...
    14. Barthlen W, Blankenstein O, Mau H et al. Evaluation of [18F]fluoro-L-DOPA positron emission tomography-computed tomography for surgery in focal congenital hyperinsulinism. J Clin Endocrinol Metab 2008; 93(3): 869-875. Go to original source... Go to PubMed...
    15. Barthlen W. Surgery in congenital hyperinsulinism-tips and tricks not only for surgeons. A practical guide. Semin Pediatr Surg 2011; 20(1): 56-59. Dostupné z DOI: <http://dx.doi.org/10.1053/j.sempedsurg.2010.10.002>. Go to original source... Go to PubMed...
    16. Banerjee I, Skae M, Flanagan SE et al. The contribution of rapid KATP channel gene mutation analysis to the clinical management of children with congenital hyperinsulinism. Eur J Endocrinol 2011; 164(5): 733-740. Dostupné z DOI: <http://dx.doi.org/10.1530/EJE-10-1136>. Go to original source... Go to PubMed...
    17. Sperling MA. New insights and new conundrums in neonatal hypoglycemia: enigmas wrapped in mystery. Diabetes 2013; 62(5): 1373-1375. Dostupné z DOI: <http://dx.doi.org/10.2337/db12-1839>. Go to original source... Go to PubMed...
    18. Shanti B, Silink M, Bhattacharya K et al. Congenital disorder of glycosylation type Ia: Heterogeneity in the clinical presentation from multivisceral failure to hyperinsulinaemic hypoglycaemia as leading symptoms in three infants with phosphomannomutase deficiency. J Inherit Metab Dis 2009; 32(Suppl 1): S241-S251. Dostupné z DOI: <http://dx.doi.org/10.1007/s10545-009-1180-2>. Go to original source... Go to PubMed...
    19. Bohles H, Sewell AA, Gebhardt B et al. Hyperinsulinaemic hypoglycaemia - leading symptom in a patient with congenital disorder of glycosylation Ia (phosphomannomutase deficiency). J Inherit Metab Dis 2001; 24(8): 858-862. Go to original source... Go to PubMed...
    20. Sun L, Eklund EA, Chung WK et al. Congenital disorder of glycosylation id presenting with hyperinsulinemic hypoglycemia and islet cell hyperplasia. J Clin Endocrinol Metab 2005; 90(7): 4371-4375. Go to original source... Go to PubMed...
    21. Baumann U, Preece MA, Green A et al. Hyperinsulinism in tyrosinaemia type I. J Inherit Metab Dis 2005; 28(2): 131-135. Go to original source... Go to PubMed...
    22. Munns CF, Batch JA. Hyperinsulinism and Beckwith-Wiedemann syndrome. Arch Dis Child Fetal Neonatal Ed 2001; 84(1): F67-F69. Go to original source... Go to PubMed...
    23. Wangler MF, An P, Feinberg AP et al. Inheritance pattern of Beckwith-Wiedemann syndrome is heterogeneous in 291 families with an affected proband. Am J Med Genet A 2005; 137(1): 16-21. Go to original source... Go to PubMed...
    24. Fukuzawa R, Umezawa A, Morikawa Y et al. Nesidioblastosis and mixed hamartoma of the liver in Beckwith-Wiedemann syndrome: case study including analysis of H19 methylation and insulin-like growth factor 2 genotyping and imprinting. Pediatr Dev Pathol 2001; 4(4): 381-390. Go to original source... Go to PubMed...
    25. Kapoor RR, James C, Hussain K. Hyperinsulinism in developmental syndromes. Endocr Dev 2009; 14: 95-113. Dostupné z DOI: <http://dx.doi.org/10.1159/000207480>. Go to original source... Go to PubMed...
    26. Alexander S, Ramadan D, Alkhayyat H et al. Costello syndrome and hyperinsulinemic hypoglycemia. Am J Med Genet A 2005; 139(3): 227-230. Go to original source... Go to PubMed...
    27. Bellanne-Chantelot C, Saint-Martin C, Ribeiro MJ et al. ABCC8 and KCNJ11 molecular spectrum of 109 patients with diazoxide-unresponsive congenital hyperinsulinism. J Med Genet 2010; 47(11): 752-759. Dostupné z DOI: <http://dx.doi.org/10.1136/jmg.2009.075416>. Go to original source... Go to PubMed...
    28. Bas VN, Ozkan M, Zenciroglu A et al. Seizure due to somatostatin analog discontinuation in a case diagnosed as congenital hyperinsulinism novel mutation. J Pediatr Endocrinol Metab 2012; 25(5-6): 553-555. Go to original source...
    29. Abdel Khalek M, Kandil E. Is octreotide safe for the management of persistent hyperinsulinemic hypoglycemia of infancy? Eur J Pediatr Surg 2011; 21(3): 188-189. Go to original source... Go to PubMed...
    30. Demirbilek H, Shah P, Arya VB et al. Long-term follow-up of children with congenital hyperinsulinism on octreotide therapy. J Clin Endocrinol Metab 2014; 99(10): 3660-3667. Dostupné z DOI: <http://dx.doi.org/10.1210/jc.2014-1866>. Go to original source... Go to PubMed...
    31. Laje P, Halaby L, Adzick NS et al. Necrotizing enterocolitis in neonates receiving octreotide for the management of congenital hyperinsulinism. Pediatr Diabetes 2010; 11(2): 142-147. Dostupné z DOI: <http://dx.doi.org/10.1111/j.1399-5448.2009.00547.x>. Go to original source... Go to PubMed...
    32. Le Quan Sang KH, Arnoux JB, Mamoune A et al. Successful treatment of congenital hyperinsulinism with long-acting release octreotide. Eur J Endocrinol 2012; 166(2): 333-339. Dostupné z DOI: <http://dx.doi.org/10.1530/EJE-11-0874>. Go to original source... Go to PubMed...
    33. Kuhnen P, Marquard J, Ernert A et al. Long-term lanreotide treatment in six patients with congenital hyperinsulinism. Horm Res Paediatr 2012; 78(2): 106-112. Go to original source... Go to PubMed...
    34. Unal S, Gonulal D, Ucakturk A et al. A novel homozygous mutation in the KCNJ11 hgene p. F315I of a neonate with congenital hyperinsulinism and succesful management by sirolimus. J Clin Res Pediatr Endocrinol 2016. Dostupné z DOI: <http://dx.doi.org/10.4274/jcrpe.2773>. Go to original source... Go to PubMed...
    35. Senniappan S, Alexandrescu S, Tatevian N et al. Sirolimus therapy in infants with severe hyperinsulinemic hypoglycemia. N Engl J Med 2014; 370(12): 1131-1137. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1310967>. Go to original source... Go to PubMed...
    36. Shah P, Arya VB, Flanagan SE et al. Sirolimus therapy in a patient with severe hyperinsulinaemic hypoglycaemia due to a compound heterozygous ABCC8 gene mutation. J Pediatr Endocrinol Metab 2015; 28(5-6): 695-699. Dostupné z DOI: <http://dx.doi.org/10.1515/jpem-2014-0371>. Go to original source... Go to PubMed...
    37. Al-Shanafey S, Alkhudhur H. Food aversion among patients with persistent hyperinsulinemic hypoglycemia of infancy. J Pediatr Surg 2012; 47(5): 895-897. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jpedsurg.2012.03.002>. Go to original source... Go to PubMed...
    38. Maiorana A, Manganozzi L, Barbetti F et al. Ketogenic diet in a patient with congenital hyperinsulinism: a novel approach to prevent brain damage. Orphanet J Rare Dis 2015; 10: 120. Dostupné z DOI: <http://dx.doi.org/10.1186/s13023-015-0342-6>. Go to original source... Go to PubMed...
    39. Adzick NS, Thornton PS, Stanley CA et al. A multidisciplinary approach to the focal form of congenital hyperinsulinism leads to successful treatment by partial pancreatectomy. J Pediatr Surg 2004; 39(3): 270-275. Go to original source... Go to PubMed...
    40. Al-Shanafey S. Laparoscopic vs open pancreatectomy for persistent hyperinsulinemic hypoglycemia of infancy. J Pediatr Surg 2009; 44(5): 957-961. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jpedsurg.2009.01.042>. Go to original source... Go to PubMed...
    41. Bax KN, van der Zee DC. The laparoscopic approach toward hyperinsulinism in children. Semin Pediatr Surg 2007; 16(4): 245-251. Go to original source... Go to PubMed...
    42. Barthlen W, Mohnike W, Mohnike K. Techniques in pediatric surgery: congenital hyperinsulinism. Horm Res Paediatr 2010; 74(6): 438-443. Dostupné z DOI: <http://dx.doi.org/10.1159/000321902>. Go to original source... Go to PubMed...
    43. Al-Nassar S, Sakati N, Al-Ashwal A et al. Persistent hyperinsulinaemic hypoglycaemia of infancy in 43 children: long-term clinical and surgical follow-up. Asian J Surg 2006; 29(3): 207-211. Go to original source... Go to PubMed...
    44. Beltrand J, Caquard M, Arnoux JB et al. Glucose metabolism in 105 children and adolescents after pancreatectomy for congenital hyperinsulinism. Diabetes Care 2012; 35(2): 198-203. Dostupné z DOI: <http://dx.doi.org/10.2337/dc11-1296>. Go to original source... Go to PubMed...
    45. Barthlen W, Mohnike W, Mohnike K. Techniques in pediatric surgery: congenital hyperinsulinism. Horm Res Paediatr 2011; 75(4): 304-310. <http://dx.doi.org/10.1159/000323532>. Go to original source... Go to PubMed...
    46. Stanley CA. Perspective on the Genetics and Diagnosis of Congenital Hyperinsulinism Disorders. J Clin Endocrinol Metab 2016; 101(3): 815-826. Dostupné z DOI: <http://dx.doi.org/10.1210/jc.2015-3651>. Go to original source... Go to PubMed...
    47. Rozenkova K, Malikova J, Nessa A et al. High Incidence of Heterozygous ABCC8 and HNF1A Mutations in Czech Patients With Congenital Hyperinsulinism. J Clin Endocrinol Metab 2015; 100(12): E1540-E1549. Dostupné z DOI: <http://dx.doi.org/10.1210/jc.2015-2763>. Go to original source... Go to PubMed...
    48. Bryan J, Munoz A, Zhang X et al. ABCC8 and ABCC9: ABC transporters that regulate K+ channels. Pflugers Arch 2007; 453(5): 703-718. Go to original source... Go to PubMed...
    49. Flanagan S, Damhuis A, Banerjee I et al. Partial ABCC8 gene deletion mutations causing diazoxide-unresponsive hyperinsulinaemic hypoglycaemia. Pediatr Diabetes 2012; 13: 285-289. Go to original source... Go to PubMed...
    50. Stanik J, Lethby M, Flanagan SE et al. Coincidence of a novel KCNJ11 missense variant R365H with a paternally inherited 6q24 duplication in a patient with transient neonatal diabetes. Diabetes Care 2008; 31(9): 1736-1737. Dostupné z DOI: <http://dx.doi.org/10.2337/dc08-0549>. Go to original source... Go to PubMed...
    51. Fernandez-Marmiesse A, Salas A, Vega A et al. Mutation spectra of ABCC8 gene in Spanish patients with Hyperinsulinism of Infancy (HI). Hum Mutat 2006; 27(2): 214. Go to original source... Go to PubMed...
    52. Ocal G, Flanagan SE, Hacihamdioglu B et al. Clinical characteristics of recessive and dominant congenital hyperinsulinism due to mutation(s) in the ABCC8/KCNJ11 genes encoding the ATP-sensitive potasium channel in the pancreatic beta cell. J Pediatr Endocrinol Metab 2011; 24(11-12): 1019-1023. Go to original source... Go to PubMed...
    53. Darendeliler F, Bas F. Hyperinsulinism in infancy - genetic aspects. Pediatr Endocrinol Rev 2006; 3(Suppl 3): S521-S526.
    54. de Lonlay P, Touati G, Robert JJ et al. Persistent hyperinsulinaemic hypoglycaemia. Semin Neonatol 2002; 7(1): 95-100. Go to original source... Go to PubMed...
    55. Delonlay P, Simon A, Galmiche-Rolland L et al. Neonatal hyperinsulinism: clinicopathologic correlation. Hum Pathol 2007; 38(3): 387-399. Go to original source... Go to PubMed...
    56. Ismail D, Smith VV, de Lonlay P et al. Familial focal congenital hyperinsulinism. J Clin Endocrinol Metab 2011; 96(1): 24-28. Dostupné z DOI: <http://dx.doi.org/10.1210/jc.2010-1524>. Go to original source... Go to PubMed...
    57. Palladino AA, Stanley CA. The hyperinsulinism/hyperammonemia syndrome. Rev Endocr Metab Disord 2010; 11(3): 171-178. Dostupné z DOI: <http://dx.doi.org/10.1007/s11154-010-9146-0>. Go to original source... Go to PubMed...
    58. Kibbey RG, Choi CS, Lee HY et al. Mitochondrial GTP insensitivity contributes to hypoglycemia in hyperinsulinemia hyperammonemia by inhibiting glucagon release. Diabetes 2014; 63(12): 4218-4229. Dostupné z DOI: <http://dx.doi.org/10.2337/db14-0783>. Go to original source... Go to PubMed...
    59. Hsu BY, Kelly A, Thornton PS et al. Protein-sensitive and fasting hypoglycemia in children with the hyperinsulinism/hyperammonemia syndrome. J Pediatr 2001; 138(3): 383-389. Go to original source... Go to PubMed...
    60. Balasubramaniam S, Kapoor R, Yeow JH et al. Biochemical evaluation of an infant with hypoglycemia resulting from a novel de novo mutation of the GLUD1 gene and hyperinsulinism-hyperammonemia syndrome. J Pediatr Endocrinol Metab 2011; 24(7-): 573-577. Go to original source... Go to PubMed...
    61. Aso K, Okano Y, Takeda T et al. Spectrum of glutamate dehydrogenase mutations in Japanese patients with congenital hyperinsulinism and hyperammonemia syndrome. Osaka City Med J 2011; 57(1): 1-9.
    62. de las Heras J, Garin I, de Nanclares GP et al. Familial hyperinsulinism-hyperammonemia syndrome in a family with seizures: case report. J Pediatr Endocrinol Metab 2010; 23(8): 827-830. Go to original source... Go to PubMed...
    63. Flanagan SE, Patch AM, Locke JM et al. Genome-wide homozygosity analysis reveals HADH mutations as a common cause of diazoxide-responsive hyperinsulinemic-hypoglycemia in consanguineous pedigrees. J Clin Endocrinol Metab 2011; 96(3): E498-E502. Dostupné z DOI: <http://dx.doi.org/10.1210/jc.2010-1906>. Go to original source... Go to PubMed...
    64. Di Candia S, Gessi A, Pepe G et al. Identification of a diffuse form of hyperinsulinemic hypoglycemia by 18-fluoro-L-3,4 dihydroxyphenylalanine positron emission tomography/CT in a patient carrying a novel mutation of the HADH gene. Eur J Endocrinol 2009; 160(6): 1019-1023. Dostupné z DOI: <http://dx.doi.org/10.1530/EJE-08-0945>. Go to original source... Go to PubMed...
    65. Christesen HB, Tribble ND, Molven A et 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 Endocrinol 2008; 159(1): 27-34. Dostupné z DOI: <http://dx.doi.org/10.1530/EJE-08-0203>. Go to original source... Go to PubMed...
    66. Cuesta-Munoz AL, Huopio H, Otonkoski T et al. Severe persistent hyperinsulinemic hypoglycemia due to a de novo glucokinase mutation. Diabetes 2004; 53(8): 2164-2168. Go to original source... Go to PubMed...
    67. 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(6): 1419-1427. Dostupné z DOI: <http://dx.doi.org/10.2337/db08-1792>. Go to original source... Go to PubMed...
    68. Pinney SE, Ganapathy K, Bradfield J et al. Dominant form of congenital hyperinsulinism maps to HK1 region on 10q. Horm Res Paediatr 2013; 80(1): 18-27. Dostupné z DOI: <http://dx.doi.org/10.1159/000351943>. Go to original source... Go to PubMed...
    69. Tegtmeyer LC, Rust S, van Scherpenzeel M et al. Multiple phenotypes in phosphoglucomutase 1 deficiency. N Engl J Med 2014; 370(6): 533-542. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1206605>. Go to original source... Go to PubMed...
    70. Meissner T, Friedmann B, Okun JG et al. Massive insulin secretion in response to anaerobic exercise in exercise-induced hyperinsulinism. Horm Metab Res 2005; 37(11): 690-694. Go to original source... Go to PubMed...
    71. Otonkoski T, Jiao H, Kaminen-Ahola N et al. Physical exercise-induced hypoglycemia caused by failed silencing of monocarboxylate transporter 1 in pancreatic beta cells. Am J Hum Genet 2007; 81(3): 467-474. Go to original source... Go to PubMed...
    72. Zhang CY, Baffy G, Perret P et al. Uncoupling protein-2 negatively regulates insulin secretion and is a major link between obesity, beta cell dysfunction, and type 2 diabetes. Cell 2001; 105(6): 745-755. Go to original source... Go to PubMed...
    73. Gonzalez-Barroso MM, Giurgea I, Bouillaud Fet al. Mutations in UCP2 in congenital hyperinsulinism reveal a role for regulation of insulin secretion. PLoS One 2008; 3(12): e3850. Dostupné z DOI: <http://dx.doi.org/10.1371/journal.pone.0003850>. Go to original source... Go to PubMed...
    74. Gupta RK, Vatamaniuk MZ, Lee CS et al. The MODY1 gene HNF-4alpha regulates selected genes involved in insulin secretion. J Clin Invest 2005; 115(4): 1006-1015. Go to original source... Go to PubMed...
    75. Pearson ER, Boj SF, Steele AM et al. Macrosomia and hyperinsulinaemic hypoglycaemia in patients with heterozygous mutations in the HNF4A gene. PLoS Med 2007; 4(4): e118. Dostupné z DOI: <http://dx.doi.org/10.1371/journal.pmed.0040118>. Go to original source... Go to PubMed...
    76. Kapoor RR, Heslegrave A, Hussain K. Congenital hyperinsulinism due to mutations in HNF4A and HADH. Rev Endocr Metab Disord 2010; 11(3): 185-191. Dostupné z DOI: <http://dx.doi.org/10.1007/s11154-010-9148-y>. Go to original source... Go to PubMed...
    77. Kapoor RR, 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): 1659-1663. Dostupné z DOI: <http://dx.doi.org/10.2337/db07-1657>. Go to original source... Go to PubMed...
    78. Conn JJ, Simm PJ, Oats JJ et al. Neonatal hyperinsulinaemic hypoglycaemia and monogenic diabetes due to a heterozygous mutation of the HNF4A gene. Aust N Z J Obstet Gynaecol 2009; 49(3): 328-330. Dostupné z DOI: <http://dx.doi.org/10.1111/j.1479-828X.2009.01009.x>. Go to original source... Go to PubMed...
    79. Stanescu DE, Hughes N, Kaplan B et al. Novel Presentations of Congenital Hyperinsulinism due to Mutations in the MODY genes: HNF1A and HNF4A. J Clin Endocrinol Metab 2012; 97(10): E2026-E2030. Dostupné z DOI: <http://dx.doi.org/10.1210/jc.2012-1356>. Go to original source... Go to PubMed...
    80. Flanagan SE, Kapoor RR, Mali G et al. Diazoxide-responsive hyperinsulinemic hypoglycemia caused by HNF4A gene mutations. Eur J Endocrinol 2010; 162(5): 987-992. Dostupné z DOI: <http://dx.doi.org/10.1530/EJE-09-0861>. Go to original source... Go to PubMed...
    81. James C, Kapoor RR, Ismail D et al. The genetic basis of congenital hyperinsulinism. J Med Genet 2009; 46(5): 289-299. Dostupné z DOI: <http://dx.doi.org/10.1136/jmg.2008.064337>. Go to original source... Go to PubMed...
    82. Staník J, Gašperíková D, Klimeš I. Monogénové poruchy sekrécie a účinku inzulínu. Bratislava. Univerzita Komenského, 2015. ISBN 978-80-223-3803-5.
    83. Staník J, Rosoľanková M, Hučková M et al. Klinický manažment a DNA diagnostika detí s kongenitálnym hyperinzulinizmom. Diabetes a obezita 2012; 12(24): 42-60.

    Return to the content


    Vnitřní lékařství

    Madam, Sir,
    please be aware that the website on which you intend to enter, not the general public because it contains technical information about medicines, including advertisements relating to medicinal products. This information and communication professionals are solely under §2 of the Act n.40/1995 Coll. Is active persons authorized to prescribe or supply (hereinafter expert).
    Take note that if you are not an expert, you run the risk of danger to their health or the health of other persons, if you the obtained information improperly understood or interpreted, and especially advertising which may be part of this site, or whether you used it for self-diagnosis or medical treatment, whether in relation to each other in person or in relation to others.

    I declare:

    1. that I have met the above instruction
    2. I'm an expert within the meaning of the Act n.40/1995 Coll. the regulation of advertising, as amended, and I am aware of the risks that would be a person other than the expert input to these sites exhibited

    No
    Yes

    If your statement is not true, please be aware
    that brings the risk of danger to their health or the health of others.