Congenital Hyperinsulinism: Review of 12 Tunisian cases

##plugins.themes.academic_pro.article.sidebar##

Published Apr 1, 2011
Download
pdf
Vol. 89 No. 4 (2011): Issue Apr 2011

##plugins.themes.academic_pro.article.main##

Hadhami Ben Turkia
Service de Pédiatrie hôpital La Rabta Tunis
Karima Brahim
Hatem Azzouz
Neji Tebib
Mohamed Slim Abdelmoula
Amel Ben Chehida
Moncef Fekih
Sadok Sayed
Nejib Kaabar
Marie Françoise Ben Dridi

Abstract

Background: Congenital hyperinsulinism in infancy (CHI) is a heterogeneous disorder with respect to genetics and response to therapy. Data on CHI are sporadic in North African population.
Aim: To characterize the clinical features and outcome of 12 Tunisian patients with CHI.
Methods: data of patients diagnosed with CHI during the period 1989-2007 were retrospectively analyzed. Diagnosis was considered whenever hyperinsulinemia ³10μ UI/ml was concomitant to hypoglycemia < 3mmol/l and/or high insulin to glucose ratio > 0.3 and/or positif glucagon test. Transient causes of hypoglycemia,
adrenal and growth hormone deficiency were excluded.
Results: There were nine infants diagnosed at a median age of 17 months and three newborns. Permanent hyperammoniemia, found in one patient, guided to leucine-sensitive hyperinsulinism. Seven patients presented with seizures, two with psychomotor delay and one with recurrent malaises. Among 42 assays of plasmatic insulin, when in hypoglycemia, 40% only were ³ 10μU/ml. Three patients resisted to diazoxide and underwent subtotal pancreatectomy complicated by diabetes mellitus in two cases and persistent hypoglycemia in one patient. Histological examination concluded to diffuse hyperplasia of pancreatic cells. Diazoxide was discontinued in four out the eight responders’ patients. Four patients died, seven patients developed variable degrees of mental retardation and five
suffered from epilepsy.
Conclusion: Early onset forms were, as reported in the literature, mostly resistant to medical therapy. The high proportion of neurological sequelae is related to diagnosis delay or to a late surgery. We focus on the importance of a precocious diagnosis and aggressive treatment of hypoglycemia.

Keywords:

Hypoglycemia, hyperinsulinism, newborns, infants, diazoxide, pancreatectomy, diabetes mellitus

##plugins.themes.academic_pro.article.details##

References

  1. Palladino AA, Bennett MJ, Stanley CA. Hyperinsulinism in infancy and childhood: when an insulin level is not always enough. Clin Chem. 2008; 54:256-63.
  2. Kapoor RR, Flanagan SE, James C, Shield J, Ellard S, Hussain K. Hyperinsulinaemic hypoglycaemia. Arch Dis Child. 2009; 94:450-7.
  3. Sempoux C, Guiot Y, Lefevre A et al. Neonatal hyperinsulinemic hypoglycemia: heterogeneity of the syndrome and keys for differential diagnosis. J Clin Endocrinol Metab 1998; 83: 1455-61.
  4. Menni F, De Lonlay P, Sevin C and al. Neurologic outcomes of 90 neonates and infants with persistent hyperinsulinemic hypoglycemia. Pediatrics 2001; 107: 476-9.
  5. Steinkrauss L, Lipman TH, Hendell CD, Gerdes M, Thornton PS, Stanley CA. Effects of hypoglycemia on developmental outcome in children with congenital hyperinsulinism. J Pediatr Nurs. 2005; 20:109-18.
  6. Hussain k. Diagnosis and management of hyperinsulinaemic hypoglycaemia of infancy. Horm Res 2008; 69: 2-13.
  7. Glaser B, Thornton P, Otonkoski T, Junien C. Genetics of neonatal hyperinsulism. Arch Dis Child Fetal Neonatal Ed 2000; 82:79-86.
  8. De Lonlay-Debeney P, Poggi-Travert F, Fournet JC et al. Clinical features of 52 neonates with hyperinsulinism. N Engl J Med 1999; 340:1169-75.
  9. 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.
  10. Al-Nassar S, Sakati N, Al-Ashwal A, Bin-Abbas B. Persistent hyperinsulinaemic hypoglycaemia of infancy in 43 children: long-term clinical and surgical follow-up. Asian J Surg.2006; 29:207-11.
  11. T. Chaabouni, T. Kammoun, M. Ben Slimen et al. Les hyperinsulinismes de l'enfant : intérêt du traitement par le diazoxide. À propos de trois cas. Ann Pediatr. 1999 ; 46 :661-8.
  12. Ben Hamouda H.,Bedoui A., Mahjoub B. et al. Hyperinsulinisme congénital du nouveau-né : évolution après pancréatectomie subtotale. Jour de Pédiatr et Puéricult 2007;20 :325-29
  13. Crétolle C, de Lonlay P, Sauvat F et al. Congenital hyperinsulinism of infancy: surgical treatment in 60 cases of focal form. Arch Pediatr. 2005;12 :258-63.
  14. Aynsley-Green A, Hussain K, Hall J, et al. Practical management of hyperinsulinism in infancy. Arch Dis Child Fetal Neonatal Ed 2000; 82:F98-F107.
  15. James C, Kapoor RR, Ismail D, Hussain K. The genetic basis of congenital hyperinsulinism. J Med Genet. 2009; 46:289-99.
  16. Damaj L, le Lorch M, Verkarre V et al. Chromosome 11p15 paternal isodisomy in focal forms of neonatal hyperinsulinism. J Clin Endocrinol Metab. 2008; 93:4941-7.
  17. MacMullen C, Fang J, Hsu BY et al. Hyperinsulinism/hyperammonemia syndrome in children with regulatory mutations in the inhibitory guanosine triphosphate-binding domain of glutamate deshydrogenase. J Clin Endocrinol Metab. 2001; 86:1782-7.
  18. Molven A, Matre GE, Duran M et al. Familial hyperinsulinemic hypoglycemia caused by a defect in the SCHAD enzyme of mitochondrial fatty acid oxidation. Diabetes. 2004; 53:221-7.
  19. Touati G, Poggi-Travert F, Ogier de Baulny H et al. Long-term treatment of persistant hyperinsulineamic hypoglycemia of infancy with Diazoxide: a retrospective review of 77 cases and analysis of efficacypredicting criteria. Eur J Pediatr 157: 628-33
  20. Leibowitz G, Glaser B, Higazi AA et al. Hyperinsulinemic hypoglycemia of infancy (nesidioblastosis) in clinical remission: high incidence of diabetes mellitus and persistent beta-cell dysfunction at long-term follow-up. J Clin Endocrinol Metab 1995; 80: 386-92.
  21. Gussinyer M, Clemente M, Cebrián R, Yeste D, Albisu M, Carrascosa A. Glucose intolerance and diabetes are observed in the long-term follow-up of nonpancreatectomized patients with persistent hyperinsulinemic hypoglycemia of infancy due to mutations in the ABCC8 gene. Diabetes Care. 2008; 31:1257-9
  22. Fekete CN, de Lonlay P, Jaubert F, et al. The surgical management of congenital hyperinsulinemic hypoglycemia in infancy. J Pediatr Surg 2004; 39: 267-9.
  23. Cherian MP, Abduljabbar MA. Persistent hyperinsulinemic hypoglycemia of infancy (PHHI): Long-term outcome following 95% pancreatectomy. J Pediatr Endocrinol Metab. 2005; 18:1441-8.
  24. Bahi-Buisson N, Roz e E, Dionisi C et al. Neurological aspects of hyperinsulinism-hyperammonaemia syndrome. Dev Med Child Neurol. 2008;50:945-9.