Disorders of Glycosylation and Movement Disorders

Chapter 19 - Disorders of Glycosylation and Movement Disorders

from Section II - A Metabolism-Based Approach to Movement Disorders and Inherited Metabolic Disorders

Published online by Cambridge University Press: 24 September 2020

Eva Morava ,

Carlos R. Ferreira and

Marc Patterson

Edited by

Darius Ebrahimi-Fakhari and

Phillip L. Pearl

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Darius Ebrahimi-Fakhari: Affiliation:
Harvard Medical School
Phillip L. Pearl: Affiliation:
Harvard Medical School

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Summary

Congenital disorders of glycosylation (CDGs) are a group of diseases characterized by an abnormal glycosylation of proteins or lipids. It is estimated that more than half of all proteins in our body are glycosylated [1]. Defined as all the sugar chains (glycans) that an organism makes, the glycome is estimated to be 102–104 times larger than the proteome [2]. Given this complexity, it is not surprising that about 2% of our genes encode for proteins that are currently known to participate in glycosylation reactions []. CDGs are classified according to the deficient glycosylated substrates, which can include proteins, lipids, or multiple substrates.

Type: Chapter
Information: Movement Disorders and Inherited Metabolic Disorders
Recognition, Understanding, Improving Outcomes
, pp. 254 - 269

DOI: https://doi.org/10.1017/9781108556767 [Opens in a new window]

Publisher: Cambridge University Press

Print publication year: 2020

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References

Apweiler, R, Hermjakob, H, Sharon, N. On the frequency of protein glycosylation, as deduced from analysis of the SWISS–PROT database. Biochim Biophys Acta. 1999;1473(1):4–8.CrossRef Google Scholar PubMed

Freeze, HH. Genetic defects in the human glycome. Nat Rev Genet. 2006;(7):537–51.Google Scholar PubMed

Freeze, HH. Understanding human glycosylation disorders: Biochemistry leads the charge. J Biol Chem. 2013;288(10):6936–45.CrossRef Google Scholar PubMed

Péanne, R, de Lonlay, P, Foulquier, F, et al. Congenital disorders of glycosylation (CDG): Quo vadis? Eur J Med Genet. 2018;61(11):643–63.Google Scholar

Kinoshita, T, Fujita, M. Biosynthesis of GPI-anchored proteins: Special emphasis on GPI lipid remodeling. J Lipid Res. 2016;57(1):6–24.Google Scholar

Jaeken, J, Vanderschueren-Lodeweyckx, M, Casaer, P, et al. Familial 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[quest]: 90. Pediatr Res. 1980;14(2):179–179.Google Scholar

Jaeken, J, van Eijk, HG, van der Heul, C, et al. Sialic acid-deficient serum and cerebrospinal fluid transferrin in a newly recognized genetic syndrome. Clin Chim Acta. 1984;144(2–3):245–7.CrossRef Google Scholar

Jaeken, J, Eggermont, E, Stibler, H. An apparent homozygous X-linked disorder with carbohydrate-deficient serum glycoproteins. Lancet. 1987;2(8572):1398.Google Scholar

Kristiansson, B, Andersson, M, Tonnby, B, Hagberg, B. Disialotransferrin developmental deficiency syndrome. Arch Dis Child. 1989;64(1):71–6.Google Scholar

Ramaekers, VT, Stibler, H, Kint, J, Jaeken, J. A new variant of the carbohydrate deficient glycoproteins syndrome. J Inherit Metab Dis. 1991;14(3):385–8.Google Scholar

Jaeken, J, De Cock, P, Stibler, H, et al. Carbohydrate-deficient glycoprotein syndrome type II. J Inherit Metab Dis. 1993;16(6):1041.CrossRef Google Scholar PubMed

Stibler, H, Westerberg, B, Hanefeld, F, Hagberg, B. Carbohydrate-deficient glycoprotein (CDG) syndrome: A new variant, type III. Neuropediatrics. 1993;24(1):51–2.Google Scholar

Stibler, H, Stephani, U, Kutsch, U. Carbohydrate-deficient glycoprotein syndrome: A fourth subtype. Neuropediatrics. 1995;26(5):235–7.Google Scholar

Jaeken, J, Schachter, H, Carchon, H, et al. Carbohydrate deficient glycoprotein syndrome type II: A deficiency in Golgi localised N-acetyl-glucosaminyltransferase II. Arch Dis Child. 1994;71(2):123–7.Google Scholar

Tan, J, Dunn, J, Jaeken, J, Schachter, H. Mutations in the MGAT2 gene controlling complex N-glycan synthesis cause carbohydrate-deficient glycoprotein syndrome type II, an autosomal recessive disease with defective brain development. Am J Hum Genet. 1996;59(4):810–7.Google Scholar

Van Schaftingen, E, Jaeken, J. Phosphomannomutase deficiency is a cause of carbohydrate-deficient glycoprotein syndrome type I. FEBS Lett. 1995;377(3):318–20.Google Scholar

Matthijs, G, Schollen, E, Pardon, E, et al. Mutations in PMM2, a phosphomannomutase gene on chromosome 16p13, in carbohydrate-deficient glycoprotein type I syndrome (Jaeken syndrome). Nat Genet. 1997;16(1):88–92.Google Scholar

Körner, C, Knauer, R, Stephani, U, Marquardt, T, Lehle, L, von Figura, K. Carbohydrate deficient glycoprotein syndrome type IV: Deficiency of dolichyl-P-Man: Man(5)GlcNAc(2)-PP-dolichylmannosyltransferase. EMBO J. 1999;18(23):6816–22.CrossRef Google Scholar

Aebi, M, Helenius, A, Schenk, B, et al. Carbohydrate-deficient glycoprotein syndromes become congenital disorders of glycosylation: An updated nomenclature for CDG. First International Workshop on CDGS. Glycoconj J. 1999;16(11):669–71.Google Scholar

Matthijs, G. Congenital disorders of glycosylation. Trends Biochem Sci. 2000;25(9):428.Google Scholar

Jaeken, J, Hennet, T, Freeze, HH, Matthijs, G. On the nomenclature of congenital disorders of glycosylation (CDG). J Inherit Metab Dis. 2008;31(6):669–72.CrossRef Google Scholar PubMed

Jaeken, J, Hennet, T, Matthijs, G, Freeze, HH. CDG nomenclature: Time for a change! Biochim Biophys Acta. 2009;1792(9):825–6.Google Scholar

van Scherpenzeel, M, Steenbergen, G, Morava, E, Wevers, RA, Lefeber, DJ. High-resolution mass spectrometry glycoprofiling of intact transferrin for diagnosis and subtype identification in the congenital disorders of glycosylation. Transl Res. 2015;166(6):639–649.e1.Google Scholar

Clayton, P, Winchester, B, Di Tomaso, E, et al. Carbohydrate-deficient glycoprotein syndrome: Normal glycosylation in the fetus. Lancet. 1993;341(8850):956.Google Scholar

Stibler, H, Skovby, F. Failure to diagnose carbohydrate-deficient glycoprotein syndrome prenatally. Pediatr Neurol. 1994;11(1):71.CrossRef Google Scholar PubMed

Vermeer, S, Kremer, HPH, Leijten, QH, et al. Cerebellar ataxia and congenital disorder of glycosylation Ia (CDG-Ia) with normal routine CDG screening. J Neurol. 2007;254(10):1356–8.Google Scholar

Abu Bakar, N, Voermans, NC, Marquardt, T, et al. Intact transferrin and total plasma glycoprofiling for diagnosis and therapy monitoring in phosphoglucomutase-I deficiency. Transl Res. 2018;199:62–76.Google Scholar

Ng, BG, Freeze, HH. Human genetic disorders involving glycosylphosphatidylinositol (GPI) anchors and glycosphingolipids (GSL). J Inherit Metab Dis. 2015;38(1):171–8.CrossRef Google Scholar PubMed

Ferreira, CR, Altassan, R, Marques-Da-Silva, D, et al. Recognizable phenotypes in CDG. J Inherit Metab Dis. 2018;41(3):541–53.CrossRef Google Scholar PubMed

Witters, P, Honzik, T, Bauchart, E, et al. Long-term follow-up in PMM2-CDG: Are we ready to start treatment trials? Genet Med. 2019;21(5):1181–8.Google Scholar

Rossi, M, Medina Escobar, A, Ameghino, L, Merello, M. Expanding the phenotype of phosphomannomutase-2 gene congenital disorder of glycosylation: Cervical dystonia. J Neurol Sci. 2017;378:52–4.Google Scholar

Knaus, A, Pantel, JT, Pendziwiat, M, et al. Characterization of glycosylphosphatidylinositol biosynthesis defects by clinical features, flow cytometry, and automated image analysis. Genome Med. 2018;10(1):3.Google Scholar

Nguyen, TTM, Murakami, Y, Sheridan, E, et al. Mutations in GPAA1, encoding a GPI transamidase complex protein, cause developmental delay, epilepsy, cerebellar atrophy, and osteopenia. Am J Hum Genet. 2017;101(5):856–65.Google Scholar

Lee, JS, Yoo, Y, Lim, BCet al. GM3 synthase deficiency due to ST3GAL5 variants in two Korean female siblings: Masquerading as Rett syndrome-like phenotype. Am J Med Genet A. 2016;170(8):2200–5.Google Scholar

Trinchera, M, Parini, R, Indellicato, R, Domenighini, R, dall’Olio, F. Diseases of ganglioside biosynthesis: An expanding group of congenital disorders of glycosylation. Mol Genet Metab. 2018;124(4):230–7.Google Scholar

Gordon-Lipkin, E, Cohen, JS, Srivastava, S, Soares, BP, Levey, E, Fatemi, A. ST3GAL5-related disorders: A deficiency in ganglioside metabolism and a genetic cause of intellectual disability and choreoathetosis. J Child Neurol. 2018;33(13):825–31.Google Scholar

Dad, R, Walker, S, Scherer, SW, et al. Febrile ataxia and myokymia broaden the SPG26 hereditary spastic paraplegia phenotype. Neurol Genet, 2017;3(3):e156.Google Scholar

Lam, C, Wolfe, L, Need, A, Shashi, V, Enns, G. NGLY1-related congenital disorder of deglycosylation. GeneReviews®. 2018; Feb 8.Google Scholar

Lam, C, Ferreira, C, Krasnewich, D, et al. Prospective phenotyping of NGLY1-CDDG, the first congenital disorder of deglycosylation. Genet Med. 2017;19(2):160–8.Google Scholar

Prietsch, V, Peters, V, Hackler, R, et al. A new case of CDG-x with stereotyped dystonic hand movements and optic atrophy. J Inherit Metab Dis. 2002;25(2):126–30.Google Scholar

Morava, E, Wevers, RA, Cantagrel, V, et al. A novel cerebello-ocular syndrome with abnormal glycosylation due to abnormalities in dolichol metabolism. Brain. 2010;133(11):3210–20.Google Scholar

Wheeler, PG, Ng, BG, Sanford, L, et al. SRD5A3-CDG: Expanding the phenotype of a congenital disorder of glycosylation with emphasis on adult onset features. Am J Med Genet A. 2016;170(12):3165–71.Google Scholar

Cantagrel, V, Lefeber, DJ, Ng, BG, et al. SRD5A3 is required for converting polyprenol to dolichol and is mutated in a congenital glycosylation disorder. Cell. 2010;142(2):203–17.Google Scholar

García-Silva, MT, Matthijs, G, Schollen, E, et al. Congenital disorder of glycosylation (CDG) type Ie. A new patient. J Inherit Metab Dis. 2004;27(5):591–600.Google Scholar

Dancourt, J, Vuillaumier-Barrot, S, de Baulny, HO, et al. A new intronic mutation in the DPM1 gene is associated with a milder form of CDG Ie in two French siblings. Pediatr Res. 2006 Jun;59(6):835–9.Google Scholar

Yang, AC, Ng, BG, Moore, SA, et al. Congenital disorder of glycosylation due to DPM1 mutations presenting with dystroglycanopathy-type congenital muscular dystrophy. Mol Genet Metab. 2013 Nov;110(3):345–51.Google Scholar

Kranz, C, Denecke, J, Lehrman, MA, et al. A mutation in the human MPDU1 gene causes congenital disorder of glycosylation type If (CDG-If). J Clin Invest. 2001 Dec;108(11):1613–9.Google Scholar

Thiel, C, Wortmann, S, Riedhammer, K, et al. Severe ichthyosis in MPDU1-CDG. J Inherit Metab Dis. 2018;41(6):1293–4.Google Scholar

Ondruskova, N, Vesela, K, Hansikova, H, et al. RFT1-CDG in adult siblings with novel mutations. Mol Genet Metab. 2012;107(4):760–2.Google Scholar

Riley, LG, Cowley, MJ, Gayevskiy, V, et al. A SLC39A8 variant causes manganese deficiency, and glycosylation and mitochondrial disorders. J Inherit Metab Dis. 2017;40(2):261–9.Google Scholar

Park, JH, Hogrebe, M, Grüneberg, M, et al. SLC39A8 deficiency: A disorder of manganese transport and glycosylation. Am J Hum Genet. 2015;97(6):894–903.Google Scholar

Corbett, MA, Schwake, M, Bahlo, M, et al. A mutation in the Golgi Qb-SNARE gene GOSR2 causes progressive myoclonus epilepsy with early ataxia. Am J Hum Genet. 2011;88(5):657–63.Google Scholar

van Egmond, ME, Verschuuren-Bemelmans, CC, Nibbeling, EA, et al. Ramsay Hunt syndrome: Clinical characterization of progressive myoclonus ataxia caused by GOSR2 mutation. Mov Disord. 2014 Jan;29(1):139–43.Google Scholar

Larson, AA, Baker, PR, Milev, MP, et al. TRAPPC11 and GOSR2 mutations associate with hypoglycosylation of α-dystroglycan and muscular dystrophy. Skelet Muscle. 2018;8(1):17.Google Scholar

Morava, E, Tiemes, V, Thiel, C, et al. ALG6-CDG: A recognizable phenotype with epilepsy, proximal muscle weakness, ataxia and behavioral and limb anomalies. J Inherit Metab Dis. 2016;39(5):713–23.Google Scholar

Morava, E, Vodopiutz, J, Lefeber, DJ, et al. Defining the phenotype in congenital disorder of glycosylation due to ALG1 mutations. Pediatrics. 2012;130(4):e1034–1039.Google Scholar

Witters, P, Cassiman, D, Morava, E. Nutritional therapies in congenital disorders of glycosylation (CDG). Nutrients. 2017;9(11):E1222.Google Scholar

Brasil, S, Pascoal, C, Francisco, R, et al. CDG therapies: From bench to bedside. Int J Mol Sci. 2018;19(5):E1304.Google Scholar