Case of diagnostics of a rare form of glycogen disease

Differential diagnosis of hypoglycemic syndrome remains an urgent problem in Pediatrics. In this article, a case of glycogen storage disease (BNG) type 0 is described in the boy, which is undoubtedly a rare pathology, which makes it difficult to diagnose this form of glycogenosis. In this description, the case of type 0 BNG is caused by a mutation in the GYS2 gene encoding the hepatic isoform of glycogen synthase. This form of the disease is usually asymptomatic in infancy. However, it can be suspected in the case when the refusal of night feeding causes certain difficulties due to the hungry ketotic hypoglycemia that occurs in the child. The first clinical symptoms appear in early childhood with the inclusion of a more varied diet in the child, increasing the intervals between meals. Symptoms of the disease are primarily caused by hypoglycemia. It should be noted that, despite the low levels of glycemia, most children do not have any mental development disorders, since the increase in the level of ketone bodies in the blood plasma provides the brain with an alternative source of energy.

1. Kanungo S, Wells K, Tribett T, et al. Glycogen metabolism and glycogen storage disorders. Ann Transl Med. 2018 Dec;6(24):474. doi: 10.21037/atm.2018.10.59

2. Ellingwood SS, Cheng A. Biochemical and clinical aspects of glycogen storage diseases. J Endocrinol. 2018;238(3):R131-R141. doi: 10.1530/JOE-18-0120

3. Gitzelmann R, Spycher MA, Feil G, et al. Liver glycogen synthase deficiency: a rarely diagnosed entity. Eur. J. Pediatr. 1996;155:561-567. doi: 10.1007/bf01957905

4. Orho M, Bosshard NU, Buist NR, et al. Mutations in the liver glycogen synthase gene in children with hypoglycemia due to glycogen storage disease type 0. J Clin Invest. 1998;102:507-515. doi: 10.1172/jci2890

5. Lewis GM, Spencer-Peet J, Stewart KM. Infantile hypoglycaemia due to inherited deficiency of glycogen synthetase in liver. Arch. Dis. Child. 1963;38:40-48. doi: 10.1136/adc.38.197.40

6. Aynsley-Green A, Williamson DH, Gitzelmann R. Hepatic glycogen synthetase deficiency. Definition of syndrome from metabolic and enzyme studies on a 9-year-old girl. Arch. Dis. Child. 1977;52:573-579. doi: 10.1136/adc.52.7.573

7. Nessa A, Kumaran A, Kirk R, et al. Mutational analysis of the GYS2 gene in patients diagnosed with ketotic hypoglycaemia. J Pediatr Endocrinol Metab. 2012;25:963-967. doi: 10.1515/jpem-2012-0165

8. Laberge AM, Mitchell GA, van de Werve G, et al. Long-term follow-up of a new case of liver glycogen synthase deficiency. Am J Med Genet A. 2003;120A:19-22. doi: 10.1002/ajmg.a.20110

9. Roach PJ, Depaoli-roach AA, Hurley TD, et al. Glycogen and its metabolism: some new developments and old themes. Biochem J. 2012;441:763-787. doi: 10.1042/bj20111416

10. Wolfsdorf JI, Weinstein DA. Glycogen storage diseases. Rev Endocr Metab Disord. 2003;4:95-102. doi: 10.1023/a:1021831621210

11. Rutledge SL, Atchison J, Bosshard NU, et al. Case report: liver glycogen synthase deficiency - a cause of ketotic hypoglycemia. Pediatrics. 2001;108:495-497. doi: 10.1542/peds.108.2.495

12. Cameron JM, Levandovskiy V, MacKay N, et al. Identification of a novel mutation in GYS1 (muscle-specific glycogen synthase) resulting in sudden cardiac death, that is diagnosable from skin fibroblasts. Mol Genet Metab. 2009;98:378-382. doi: 10.1016/j.ymgme.2009.07.012

13. Sukigara S, Liang WC, Komaki H, et al. Muscle glycogen storage disease 0 presenting recurrent syncope with weakness and myalgia. Neuromuscul Disord. 2012;22:162-165. doi: 10.1016/j.nmd.2011.08.008

14. Szymanska E, Rokicki D, Wgtrobinska U, et al. Pediatric patient with hyperketotic hypoglycemia diagnosed with glycogen synthase deficiency due to the novel homozygous mutation in GYS2. Mol Genet Metab Rep. 2015;4:83-86. doi: 10.1016/j.ymgmr.2015.07.003

15. Hacihamdioglu B, Özgürhan G, Çaran B, et al. Glycogen storage disease type 0 due to a novel frameshift mutation in glycogen synthase 2 (GYS2) gene in a child presenting with fasting hypoglycemia and postprandial hyperglycemia. Turkish Journal of Pediatrics. 2018;60:581-583. doi: 10.24953/turkjped.2018.05.018

16. Soggia AP, Correa-Giannell ML, Fortes MA, et al. A novel mutation in the glycogen synthase 2 gene in a child with glycogen storage disease type 0. BMC Med Genet. 2010;11(1). doi: 10.1186/1471-2350-11-3

17. Weinstein DA, Correia CE, Saunders AC, et al. Hepatic glycogen synthase deficiency: an infrequently recognized cause of ketotic hypoglycemia. Mol Genet Met. 2006;87(4):284-288. doi: 10.1016/j.ymgme.2005.10.006

18. Kasapkara £S, Aycan Z, Agoglu E, et al. The variable clinical phenotype of three patients with hepatic glycogen synthase deficiency. J Pediatr Endocrinol Metab. 2017;30(4):459-62. doi: 10.1515/jpem-2016-0317

19. Spiegel R, Mahamid J, Orho-Melander M, et al. The variable clinical phenotype of liver glycogen synthase deficiency. J Pediatr Endocrinol Metab. 2007;20:1339-1342. doi: 10.1515/jpem.2007.20.12.1339

20. Bachrach BE, Weinstein DA, Orho-Melander M, et al. Glycogen synthase deficiency (glycogen storage disease type 0) presenting with hyperglycemia and glucosuria: report of three new mutations. J Pediatr. 2002 Jun;140(6):781-783. doi: 10.1067/mpd.2002.124317

21. Brown LM, Corrado MM, van der Ende RM, et al. Evaluation of glycogen storage disease as a cause of ketotic hypoglycemia in children. J Inherit Metab Dis. 2015;38:489-493. doi: 10.1007/s10545-014-9744-1