Hypoglycemia in CDG patients due to PMM2 mutations: Follow up on hyperinsulinemic patients

Abstract

Background: Phosphomannomutase 2 deficiency (PMM2-CDG) is the most common congenital disorder of glycosylation (CDG). Hypoglycemia has been reported in various CDG including PMM2-CDG. The frequency and etiology of hypoglycemia in PMM2-CDG are not well studied.; Methods: We conducted a systematic review of the literature on genetically and/or biochemically confirmed PMM2-CDG patients who developed hypoglycemia. Prospective follow-up information on the patients who received diazoxide therapy was collected and evaluated.; Results: A total of 165 peer-reviewed articles reporting on 933 PMM2-CDG patients were assessed. Hypoglycemia was specifically mentioned only in 23 of these patients (2.5%). Hyperinsulinism was identified in 10 patients (43% of all hypoglycemic patients). Among these 10 patients, seven were successfully treated with diazoxide. However, most patients remained on therapy longer than a year to stay free of hypoglycemia.; Conclusion: Hypoglycemia is a rarely reported finding in patients with PMM2-CDG. Diazoxide-responsive hyperinsulinism was found to have a good prognosis on medication in our PMM2-CDG patients with hypoglycemia. No genotype-phenotype correlation was observed with respect to hyperinsulinism. A prospective study should be undertaken to explore the hypothesis that hypoglycemia is underdiagnosed in PMM2-CDG and to evaluate whether hyperinsulinism is always associated with hypoglycemia. (© 2019 The Authors. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.)eCollection. Cited Medium: Print. NLM ISO Abbr: JIMD Rep. PubMed Central ID: PMC7012739. Linked References: Am J Med Genet A. 2007 Jun 15;143A(12):1371-8. (PMID: 17506107); Mol Genet Metab. 2008 Aug;94(4):481-4. (PMID: 18571450); J Inherit Metab Dis. 2001 Dec;24(8):858-62. (PMID: 11916319); Mol Genet Metab. 2013 Nov;110(3):411-3. (PMID: 24063868); Am J Hum Genet. 2007 Mar;80(3):433-40. (PMID: 17273964); Acta Clin Belg. 2016 Dec;71(6):435-437. (PMID: 27351072); Mol Genet Metab. 2011 May;103(1):101-3. (PMID: 21334936); JIMD Rep. 2019 Nov 25;51(1):76-81. (PMID: 32071842); Mol Genet Metab. 2017 Mar;120(3):235-242. (PMID: 28122681); Endocr Rev. 2017 Oct 1;38(5):379-431. (PMID: 28973479); Am J Med Genet A. 2008 Feb 1;146A(3):389-92. (PMID: 18203160); J Perinatol. 2007 Dec;27(12):802-4. (PMID: 18034167); Biochim Biophys Acta. 2009 Sep;1792(9):841-3. (PMID: 19101627); N Engl J Med. 2014 Feb 6;370(6):533-42. (PMID: 24499211); Acta Paediatr. 2002;91(10):1065-72. (PMID: 12434892); Fetal Diagn Ther. 2009;25(1):54-7. (PMID: 19176971); Pediatr Radiol. 1999 Mar;29(3):194-8. (PMID: 10201039); J Inherit Metab Dis. 2015 Mar;38(2):207-9. (PMID: 25288126); J Biol Chem. 2002 Jul 12;277(28):25416-22. (PMID: 11994306); Genet Med. 2001 Nov-Dec;3(6):393-8. (PMID: 11715002); Mol Genet Metab. 2008 Apr;93(4):444-9. (PMID: 18093857); Genet Med. 2019 May;21(5):1181-1188. (PMID: 30293989); J Inherit Metab Dis. 2017 Jul;40(4):569-586. (PMID: 28484880); J Clin Endocrinol Metab. 2005 Jul;90(7):4371-5. (PMID: 15840742); J Inherit Metab Dis. 2009 Dec;32 Suppl 1:S241-51. (PMID: 19396570); J Inherit Metab Dis. 2011 Aug;34(4):923-7. (PMID: 21541726); Eur J Med Genet. 2018 Nov;61(11):643-663. (PMID: 29079546); Pediatr Cardiol. 2012 Jun;33(5):827-30. (PMID: 22374380); J Med Genet. 2001 Jan;38(1):14-9. (PMID: 11134235); PLoS One. 2013 Sep 11;8(9):e75189. (PMID: 24040400); J Pediatr. 2002 Nov;141(5):695-700. (PMID: 12410200). Linking ISSN: 21928304. Subset: PubMed not MEDLINE; Date of Electronic Publication: 2019 Nov 25. Current Imprints: Publication: 2019- : [Hoboken, NJ] : Wiley; Original Imprints: Publication: Berlin : SSIEM and Springer-Verlag, c2011. <br />