Martínez-Duncker I, Palomares-Aguilera L, Sánchez-Francia D, Mollicone R, Ibarra-González MCI

Idioma: Español
Referencias bibliográficas: 39
Paginas: 78-88
Archivo PDF: 423.07 Kb.

RESUMEN

Más de la mitad de las proteínas humanas son modificadas (glicosiladas) a nivel co- y post-traduccional por la unión específica de oligosacáridos (glicanos) mediada por la acción de glicosiltransferasas. Los glicanos participan en el control de calidad, tráfico y función de las proteínas glicosiladas (glicoproteínas). Se han descrito múltiples defectos congénitos humanos en las principales vías de glicosilación (N- y O-glicosilación). En 1980 se describió el primer subtipo clínico y a partir de entonces se han ido sumando nuevos subtipos. En la actualidad se conocen otros 35 más y, debido a que centenas de proteínas participan en este proceso, se cree que nuevos subtipos serán identificados en los próximos años. La sospecha clínica de estos trastornos se da ante una enfermedad congénita, generalmente multisistémica y de severidad variable. El objetivo de esta revisión es presentar al médico los datos clínicos que le permitan sospechar un trastorno congénito de la glicosilación (CDG congenital disorders of glycosylation, en inglés), encuadrar los subtipos más probables de acuerdo a su presentación e incorporar al abordaje clínico los estudios moleculares necesarios para confirmar el diagnóstico, evaluar un potencial tratamiento y determinar un pronóstico.

REFERENCIAS (EN ESTE ARTÍCULO)

1. Bohne A, von der Lieth CW, Glycosylation of proteins: a computer based method for the rapid exploration of conformational space of N-glycans. Pac Symp Biocomput, 2002;285-96.

2. Freeze HH, Disorders in protein glycosylation and potential therapy: tip of an iceberg? J Pediatr, 1998;133:593–600.

3. Perez-Cerda C, Ugarte M. Congenital disorders of glycosylation.Their diagnosis and treatment. Rev Neurol, 2006;43(Suppl1): S145-56.

4. Jaeken J, Vanderschueren-Lodeweyckx M, Casaer P, Snoeck L, Corbeel L, Eggermont E, Familiar psychomotor retardation with markedly fluctuating serum prolactin, FSH and GH levels, partial TBG deficiency, increased serum arylsulphatase A and increased CSF protein: a new syndrome? . Pediatr Res 1980;14:179.

5. Vilaseca MA, Artuch R, Briones P. Congenital disorders of glycosylation: state of the art and Spanish experience. Med Clin (Barc) 2004;122(18):707-16.

6. Helenius J, Aebi M, Transmembrane movement of dolichol linked carbohydrates during N-glycoprotein biosynthesis in the endoplasmic reticulum. Semin Cell Dev Biol, 2002;13(3):171-8.

7. Freeze HH, Aebi M, Altered glycan structures: the molecular basis of congenital disorders of glycosylation. Curr Opin Struct Biol, 2005;15(5):490-8.

8. Lubke T, Marquardt T, Etzioni A, Hartmann E, von Figura K,Korner C, Complementation cloning identifies CDG-IIc, a new type of congenital disorders of glycosylation, as a GDP-fucose transporter deficiency. Nat Genet, 2001;28(1):73-6.

9. Ungar D, Oka T, Krieger M, Hughson FM, Retrograde transport on the COG railway. Trends Cell Biol, 2006;16(2):113-20.

10. Foulquier F, Vasile E, Schollen E, et al., Conserved oligomeric Golgi complex subunit 1 deficiency reveals a previously uncharacterized congenital disorder of glycosylation type II. Proc Natl Acad Sci U S A, 2006;103(10):3764-9.

11. Wopereis S, Grunewald S, Huijben KM, et al., Transferrin and apolipoprotein C-III isofocusing are complementary in the diagnosis of N- and O-glycan biosynthesis defects. Clin Chem, 2007;53(2):180-7.

12. Chacko BK, Appukuttan PS, Peanut (Arachis hypogaea) lectin recognizes alpha-linked galactose, but not N-acetyl lactosami-ne in N-linked oligosaccharide terminals. Int J Biol Macromol,2001;28(5):365-71.

13. Hendriksz CJ, McClean P, Henderson MJ, et al., Successful treatment of carbohydrate deficient glycoprotein syndrome type 1b with oral mannose. Arch Dis Child 2001;85(4):339-40.

14. Rush JS, Panneerselvam K, Waechter CJ, Freeze HH, Mannose supplementation corrects GDP-mannose deficiency in cultured fibroblasts from some patients with Congenital Disorders of Glycosylation (CDG). Glycobiology, 2000;10(8):829-35.

15. Westphal V, Kjaergaard S, Davis JA, Peterson SM, Skovby F,Freeze HH, Genetic and metabolic analysis of the first adult with congenital disorder of glycosylation type Ib: long-term outcome and effects of mannose supplementation. Mol Genet Metab 2001;73(1):77-85.

16. Marquardt T, Luhn K, Srikrishna G, Freeze HH, Harms E,Vestweber D, Correction of leukocyte adhesion deficiency type II with oral fucose. Blood 1999;94(12):3976-85.

17. Hidalgo A, Ma S, Peired AJ, Weiss LA, Cunningham-Rundles C, Frenette PS, Insights into leukocyte adhesion deficiency type 2 from a novel mutation in the GDP-fucose transporter gene. Blood 2003;101(5):1705-12.

18. Sturla L, Puglielli L, Tonetti M, et al., Impairment of the Golgi GDP-L-fucose transport and unresponsiveness to fucose replacement therapy in LAD II patients. Pediatr Res 2001;49(4):537-42.

19. Wopereis S, Lefeber DJ, Morava E, Wevers RA, Mechanisms in protein O-glycan biosynthesis and clinical and molecular aspects of protein O-glycan biosynthesis defects: a review. Clin Chem 2006;52(4):574-600.

20. Krane SM, Pinnell SR, Erbe RW, Lysyl-protocollagen hydroxylase deficiency in fibroblasts from siblings with hydroxylysine-de- ficient collagen. Proc Natl Acad Sci 1972;69(10):2899-903.

21. Yeowell HN, Walker LC, Farmer B, Heikkinen J, Myllyla R,Mutational analysis of the lysyl hydroxylase 1 gene (PLOD) in six unrelated patients with Ehlers-Danlos syndrome type VI: prenatal exclusion of this disorder in one family. Hum Mutat 2000;16(1):90.

22. Okajima T, Fukumoto S, Furukawa K, Urano T, Molecular basis for the progeroid variant of Ehlers-Danlos syndrome. Identification and characterization of two mutations in galactosyltransferase I gene. J Biol Chem 1999;274(41):28841-4.

23. Seidler DG, Faiyaz-Ul-Haque M, Hansen U, et al., Defective glycosylation of decorin and biglycan, altered collagen structure, and abnormal phenotype of the skin fibroblasts of an Ehlers-Danlos syndrome patient carrying the novel Arg270Cys substitution in galactosyltransferase I (beta4GalT-7). J Mol Med 2006;84(7):583-94.

24. Faiyaz-Ul-Haque M, Zaidi SH, Al-Ali M, et al., A novel missense mutation in the galactosyltransferase-I (B4GALT7) gene in a family exhibiting facioskeletal anomalies and Ehlers-Danlos syndrome resembling the progeroid type. Am J Med Genet A 2004;128(1):39-45.

25. Lind T, Tufaro F, McCormick C, Lindahl U, Lidholt K, The putative tumor suppressors EXT1 and EXT2 are glycosyltransferases required for the biosynthesis of heparan sulfate. J Biol Chem, 1998;273(41):26265-8.

26. Quentin E, Gladen A, Roden L, Kresse H, A genetic defect in the biosynthesis of dermatan sulfate proteoglycan: galactosyltransferase I deficiency in fibroblasts from a patient with a progeroid syndrome. Proc Natl Acad Sci 1990;87(4):1342-6.

27. Francannet C, Cohen-Tanugi A, Le Merrer M, Munnich A, Bonaventure J, Legeai-Mallet L, Genotype-phenotype correlation in hereditary multiple exostoses. J Med Genet, 2001;38(7):430-4.

28. Ahn J, Ludecke HJ, Lindow S, et al., Cloning of the putative tumour suppressor gene for hereditary multiple exostoses (EXT1). Nat Genet, 1995;11(2):137-43.

29. Philippe C, Porter DE, Emerton ME, Wells DE, Simpson AH,Monaco AP, Mutation screening of the EXT1 and EXT2 genes in patients with hereditary multiple exostoses. Am J Hum Genet 1997;61(3):520-8.

30. Winder SJ, The complexities of dystroglycan. Trends Biochem Sci 2001;26(2):118-24.

31. Moore SA, Saito F, Chen J, et al., Deletion of brain dystroglycan recapitulates aspects of congenital muscular dystrophy. Nature 2002;418(6896):422-5.

32. Guglieri M, Magri F, Comi GP, Molecular etiopathogenesis of limb girdle muscular and congenital muscular dystrophies: boundaries and contiguities. Clin Chim Acta 2005;361(1-2):54-79.

33. Mendell JR, Boue DR, Martin PT, The congenital muscular dystrophies: recent advances and molecular insights. Pediatr Dev Pathol 2006;9(6):427-43.

34. Longman C, Brockington M, Torelli S, et al., Mutations in the human LARGE gene cause MDC1D, a novel form of congenital muscular dystrophy with severe mental retardation and abnormal glycosylation of alpha-dystroglycan. Hum Mol Genet 2003;12(21):2853-61.

35. Endo T, Manya H, Defect in glycosylation that causes muscular dystrophy. Methods Enzymol 2006;417:137-52.

36. Topaz O, Bergman R, Mandel U, et al., Absence of intraepidermal glycosyltransferase ppGalNac-T3 expression in familial tumoral calcinosis. Am J Dermatopathol 2005;27(3):211- 5.

37. Topaz O, Shurman DL, Bergman R, et al., Mutations in GALNT3,encoding a protein involved in O-linked glycosylation, cause familial tumoral calcinosis. Nat Genet 2004;36(6):579-81.

38. Martinez-Duncker I, Dupre T, Piller V, et al., Genetic complementation reveals a novel human congenital disorder of glycosylation of type II, due to inactivation of the Golgi CMPsialic acid transporter. Blood 2005;105(7):2671-6.

39. Sommers LW, Hirschberg CB, Transport of sugar nucleotides into rat liver Golgi. A new Golgi marker activity. J Biol Chem 1982;257(18):10811-7.