Clinical characteristics and phenotype-genotype review of 25 Omani children with congenital hyperinsulinism in infancy. A one-decade single-center experience

Maryam K. Al-Badi, Hanan S. Al-Azkawi, Mouza S. Al-Yahyaei, Waad A. Mula-Abed, Aisha M. Al-Senani

Abstract


Objectives: To report the genotype-phenotype characteristics, demographic features and clinical outcome of Omani patients with congenital hyperinsulinism (CHI).

 

Methods: We retrospectively analyzed the clinical, biochemical, genotypical, phenotypical characteristics and outcomes of  children with CHI who were presented to the pediatric endocrine team in the Royal Hospital, Muscat, Oman between January 2007 and December 2016.

 

Results: Analysis of 25 patients with CHI genetically revealed homozygous mutation in ABCC8 in 23 (92%) patients and 2 patients (8%) with compound heterozygous mutation in ABCC8. Fifteen (60%) patients underwent subtotal pancreatectomy as medical therapy failed and 2 (8%) patients showed response to medical therapy. Three patients expired during the neonatal period, 2 had cardiomyopathy and sepsis, and one had sepsis and severe metabolic acidosis. Out of the 15 patients who underwent pancreatectomy, 6 developed diabetes mellitus, 6 continued to have hypoglycemia and required medical therapy and one had pancreatic exocrine dysfunction post-pancreatectomy, following up with gastroenterology clinic and was placed on pancreatic enzyme supplements, while 2 patients continued to have hypoglycemia and both had abdominal MRI and 18-F-fluoro-L-DOPA positron emission tomography scan (PET-scan), that showed  persistent of the disease and started on medical therapy.

 

Conclusion:  Mutation in ABCC8 is the most common cause of CHI and reflects the early age of presentation. There is a need for early diagnosis and appropriate therapeutic strategy.

 

 

Saudi Med J 2019; Vol. 40 (7): 669-674
doi: 10.15537/smj.2019.7.24291



How to cite this article:
Al-Badi MK, Al-Azkawi HS, Al-Yahyaei M, Mula-Abed W, Al-Senani A. Clinical characteristics and phenotype-genotype review of 25 Omani children with congenital hyperinsulinism in infancy: A one-decade single-center experience. Saudi Med J 2019; 40 (7): 669-674. doi: 10.15537/smj.2019.7.24291.

 


Keywords


Congenital Hyperinsulinism in Infancy (CHI); Persistent Hyperinsulinemic Hypoglaycemia of Infancy (PHHI); hypoglycemia, Pancreatectomy; KATP channel; ABCC8 gene

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References


Palladino AA, Bennett MJ, Stanley CA. Hyperinsulinism in infancy and childhood: when an insulin level is not always enough. Clin Chem 2008 Feb;54(2):256-63.

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: 109-118.

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

Hussain K, Aynsley-Green A. Management of hyperinsulinism in infancy and childhood. Ann Med 2000; 32: 544-551.

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

Kapoor RR, Flanagan SE, Arya VB, Shield JP, Ellard S, Hussain K. Clinical and molecular characterization of 300 patients with congenital hyperinsulinism. Eur J Endocrinol 2013; 168: 557-564.

Kapoor RR, Heslegrave A, Hussain K. Congenital hyperinsulinism due to mutations in HNF4A and HADH. Rev Endocr Metab Disord 2010;11: 185- 191.

Flanagan SE, Kapoor RR, Hussain K. Genetics of congenital hyperinsulinemic hypoglycemia. Semin Pediatr Surg 2011; 20: 13-17.

Ackermann AM LC, Freeze HH, Ficicioglu C, Kaestner KH, Stanley CA. Hypoglycemia due to lower threshold of glucose-stimulated insulin secretion in phosphoglucomutase 1 deficiency. Platform Presentation at: Annual meeting of the Pediatric Academic Societies. San Diego(CA). University of Pennsylvania; 2015.

Cabezas OR, Flanagan SE, Stanescu H, García-Martínez E, Caswell R, Lango-Allen H, et al. Polycystic kidney disease with hyperinsulinemic hypoglycemia caused by a promoter mutation in phosphomannomutase 2. J Am Soc Nephrol 2017; 28: 2529-2539.

Pinney SE, Ganapathy K, Bradfield J, Stokes D, Sasson A, Mackiewicz K. Dominant form of congenital hyperinsulinism maps to HK1 region on 10q. Horm Res Paediatr 2013; 80: 18-27.

Tegtmeyer LC, Rust S, van Scherpenzeel M, Ng BG, Losfeld ME, Timal S, et al. Multiple phenotypes in phosphoglucomutase 1 deficiency. N Engl J Med 2014; 370: 533-542.

Giri D, Vignola ML, Gualtieri A, Scagliotti V, McNamara P, Peak M, et al. Novel FOXA2 mutation causes Hyperinsulinism, Hypopituitarism with Craniofacial and Endoderm- derived organ abnormalities. Hum Mol Genet 2017; 26: 4315-4326.

Flanagan SE, Vairo F, Johnson MB, Caswell R, Laver TW, Lango Allen H, et al. A CACNA1D mutation in a patient with persistent hyperinsulinaemic hypoglycaemia, heart defects, and severe hypotonia. Pediatr Diabetes 2017; 18: 320-323.

Senniappan S, Shanti B, James C, Hussain K. Hyperinsulinaemic hypoglycaemia: genetic mechanisms, diagnosis and management. J Inherit Metab Dis 2012; 35: 589-601.

Thomas PM, Cote GJ, Wohllk N, Haddad B, Mathew PM, Rabl W, et al. Mutations in the sulfonylurea receptor gene in familial persistent hyperinsulinemic hypoglycemia of infancy. Science 1995; 268: 426-429.

Kane C, Shepherd RM, Squires PE, Johnson PR, James RF, Milla PJ, et al. Loss of functional KATP channels in pancreatic beta-cells causes persistent hyperinsulinemic hypoglycemia of infancy. Nat Med 1996; 2: 1344-1347.

Glaser B. Lessons in human biology from a monogenic pancreatic beta cell disease. J Clin Invest 2011; 121: 3821-3825.

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.

Otonkoski T, Ammala C, Huopio H, Cote GJ, Chpman J, Cosqrove K, et al. A point mutation inactivating the sulphonylurea receptor causes the severe form of persistent hyperinsulinaemic hypoglycemia of infancy in Finland. Diabetes 199948: 408-415.

Al-Nasser S, Sakati N, Al-Ashwal A, Bin Abbas B. Persistent hyperinsulinaemic hypoglycemia of infancy in 43 children: long term clinical and surgical follow-up. Asian J Surg 2006: 29: 207-211.

Pierro A, Nah SA. Surgical management of congenital hyperinsulinism of infancy. Semin Pediatr Surg 2011; 20: 50-53.

Al-Thihli K, Al-Murshedi F, Al-Hashmi N, Al-Mamari W, Mazharul M, Al-Yahyaee S. Consanguinity, endogamy and Inborn Errors of Metabolism in Oman: a Cross sectional Study. Hum Hered 2014; 77: 183-188.

Rajab A, Abdel Aty MA, Jaju S, Morsi M, Al-Khaurasi H, Al-Shekaili W. National reproductive Health SURVEY 2008. Ministry of Health: Muscat (Oman); 2008.

Snider KE, Becker S, Boyajian L, Shyng SL, MacMullen C, Hughes N, et al. Genotype and phenotype correlations in 417 children with congenital hyper-insulinism. J Clin Endocrinol Metab 2013; 98: E355-E363.

Demirbilek H, Arya VB, Ozbek MN, Akinci A, Dogan M, Demirel F, et al. Clinical characteristics and phenotype–genotype analysis in Turkish patients with congenital hyperinsulinism; predominance of recessive KATP channel mutations. Eur J Endocrinol 2014; 170: 885-892.

Akcay T, Taskin N, Ulucan K, Kirac D. Congenital hyperinsulinism and cardiomyopathy. Fetal Pediatr Pathol 2012; 31: 190.

Huang T, Kelly A, Becker SA, Cohen MS, Stanley CA. Hypertrophic cardiomyopathy in neonates with congenital hyperinsulinism. Arch Dis Child Fetal Neonatal Ed 2013; 98: F351-F354.

Kühnen P, Marquard J, Ernert A, Meissner T, Raile K, Wannenmacher G, et al. Long-term lanreotide treatment in six patients with congenital hyperinsulinism. Horm Res Paediatr 2012; 78: 106-112.

Shah P, Arya VB, Flanagan SE, Morgan K, Ellard S, Senniappan S, 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: 695-699.

Senniappan S, Alexandrescu S, Tatevian N, Shah P, Arya V, Flanagan S, et al. Sirolimus therapy in infants with severe hyperinsulinemic hypoglycemia. N Engl J Med 2014; 370: 1131-1137.

Banerjee I, De Leon D, Dunne MJ. Extreme caution on the use of sirolimus for the congenital hyperinsulinism in infancy patient. Orphanet J Rare Dis 2017; 12: 70.


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