Congenital disorder of glycosilation PMM2-CDG

Congenital glycosylation disorders represent a group of genetically determined diseases which violate the synthesis and addition of glycans to glycoproteins and glycolipids, and also the synthesis of glycosylphosphatidyl inositol. The most common defects are the defects of protein N-glycosylation. Jaken syndrome, a congenital disorder of PMM2-CDG glycosylation, is the most commonly diagnosed type (about 800 cases worldwide). However, there are only a few descriptions of clinical cases in the Russian literature. The article presents a clinical observation of a child with this type of congenital glycosylation disorder due to a defect in phosphomannomtase 2 (PMM2 gene). The diagnose was based on the combination of clinical, laboratory and instrumental data: a characteristic phenotype, hyperinsulinism, delayed physical and psychomotor development, neurological manifestations, coagulopathy, liver damage, exudative enteropathy, abnormal forms of transferrin, PMM2 gene mutations associated with Jaken’s syndrome. For the first time the authors described positive clinical and laboratory dynamics due to the inclusion of D-mannose to the therapy for this type of congenital glycosylation disorder.

1. Peanne R., de Lonlay P., Foulquier F., Kornak U., Lefeber D.J., Morava E. et al. Congenital disorders of glycosylation (CDG): Quo vadis? Eur J Med Genet 2017. DOI: 10.1016/j.ejmg.2017.10.012

2. Rymen D., Jaeken J. Skin manifestations in CDG. J Inherit Metab Dis 2014; 37: 699–708. DOI: 10.1007/s10545-014-9678-7

3. Freeze H.H., Chong J.X., Bamshad M.J., Ng B.G. Solving glycosylation disorders: fundamental approaches reveal complicated pathways. Am J Hum Genet 2014; 94: 161–175. DOI: 10.1016/j.ajhg.2013.10.024.

4. Jaeken J., Péanne R. What is new in CDG? J Inherit Metab Dis 2017; 40(4): 569–586. DOI: 10.1007/s10545-017-0050-6

5. Chang I.J., He M., Lam C.T. Congenital disorders of glycosylation. Ann Transl Med 2018; 6(24): 477. DOI: 10.21037/atm.2018.10.45

6. Hennet T. Diseases of glycosylation beyond classical congenital disorders of glycosylation. Biochim Biophys Acta Gen Subj 2012; 1820: 1306–1317. DOI: 10.1016/j.bbagen.2012.02.001

7. Marques-da-Silva D., dos Reis Ferreira V., Monticelli M., Janeiro P., Videira P.A., Witters P. et al. Liver involvement in congenital disorders of glycosylation (CDG). A systematic review of the literature. J Inherit Metab Dis 2017; 40: 195–207. DOI: 10.1007/s10545-016-0012-4

8. Van Scherpenzeel M., Willems E., Lefeber D.J. Clinical diagnostics and therapy monitoring in the congenital disorders of glycosylation. Glycoconj J 2016; 33: 345–358. DOI: 10.1007/s10719-015-9639-x

9. Иванов Д.О., Новикова В.П., Похлебкина А.А. Врожденные нарушения гликозилирования. Педиатр 2018; 9(3): 5–15. [Ivanov D.O., Novikova V.P., Pohlebkina A.A. Congenital glycosylation disorders. Pediatr 2018; 9(3): 5–15 (in Russ.)] DOI: 10.17816/PED935-15

10. Jaeken J., van Eijk H.G., van der Heul C., Corbeel L., Eeckels R., Eggermont E. Sialic aciddeficient serum and cerebrospinal fluid transferrin in a newly recognized genetic syndrome. Clin Chim Acta 1984; 144: 245–247. DOI: 10.1016/0009-8981(84)90059-7

11. Гусина А.А., Зиновик А.В., Мясников С.О., Калинина Е.А., Мотюк И.Н., Гусина Н.Б. Болезнь Жакена: обзор литературы и описание клинического случая. Педиатрия. Восточная Европа 2019; 7(1): 134–150. [Gusina A., Zinovik A., Myasnikov S., Kalinina E., Motyuk I., Gusina N. Jaeken Disease: Literature Review and Description of the Clinical Case. Paediatrics. Eastern Europe 2019; 7(1): 134–150 (in Russ.)]

12. Brasil S., Pascoal C., Francisco R., Marques-da-Silva D., Andreotti G., Videira P.a A., et al. CDG Therapies: From Bench to Bedside. Int J Mol Sci 2018; 19: 1304. DOI: 10.3390/ijms19051304

13. Акоев Ю.С., Мигали А.В., Журкова Н.В., Кондакова О.Б., Рославцева Е.А., Пинаева А.Р. и др. Синдром наруше- ния гликозилирования 1b типа: диагностика и лечение. Педиатрическая фармакология 2008; 5(5): 31–33. [Akoev Yu.S., Migali A.V., Zhurkova N.V., Kondakova O.B., Roslavceva E.A., Pinaeva A.R et al. Syndrome of glycosylation disorders type 1 b: diagnosis and treatment Pediatricheskaja farmakologija 2008; 5(5): 31–33 (in Russ.)]

14. Jaeken J., Matthijs G. Congenital disorders of glycosylation: a rapidly expanding disease family. Annu Rev Genomics Hum Genet 2007; 8: 261–278. DOI: 10.1146/annurev.genom.8.080706.092327

15. Schiff M., Roda C., Monin M.L., Arion A., Barth M., Bednarek N. et al. Clinical, laboratory and molecular findings and long-term follow-up data in 96 French patients with PMM2-CDG ( phosphomannomutase 2-congenital disorder of glycosylation) and review of the literature. J Med Genet 2017; 54: 843–851. DOI: 10.1136/jmedgenet-2017-104903

16. Barone R., Carrozzi M., Parini R., Battini R., Martinelli D., Elia M. et al. A nationwide survey of PMM2-CDG in Italy: high frequency of a mild neurological variant associated with the L32R mutation. J Neurol 2015; 262: 154–164. DOI: 10.1007/s00415-014-7549-7

17. https://rarediseases.org/rare-diseases/pmm2-cdg

18. Albahri Z. Congenital Disorders of Glycosylation: A Review. Am J Pediatrics 2015; 1(2): 6–28. DOI: 10.11648/j.ajp.20150102.11

19. Marquardt T., Denecke J. Congenital disorders of glycosylation: review of their molecular bases, clinical presentations and specific therapies. Eur J Pediatr 2003; 162(6): 359–379. DOI: 10.1007/s00431-002-1136-0

20. Pancho C., Garcia-Cazorla A., Varea V., Artuch R., Ferrer I., Vilaseca M.A. et al. Congenital disorder of glycosylation type Ia revealed by hypertransaminasemia and failure to thrive in a young boy with normal neurodevelopment. J Pediatr Gastroenterol Nutr 2005; 40(2): 230–232.

21. Jaeken J. Congenital disorders of glycosylation. Ann N Y Acad Sci 2010; 1214: 190–198. Review. DOI: 10.1111/j.1749-6632.2010.05840.x

22. Babovic-Vuksanovic D., O’Brien J.F. Laboratory diagnosis of congenital disorders of glycosylation type I by analysis of transferrin glycoforms. Mol Diagn Ther 2007; 11: 303–311. DOI: 10.1007/BF03256251