Browse > Article
http://dx.doi.org/10.5734/JGM.2021.18.1.16

GLB1-related disorders: GM1 gangliosidosis and Morquio B disease  

Cho, Sung Yoon (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine)
Jin, Dong-Kyu (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine)
Publication Information
Journal of Genetic Medicine / v.18, no.1, 2021 , pp. 16-23 More about this Journal
Abstract
GLB1-related disorders comprise two phenotypically unique disorders: GM1 gangliosidosis and Morquio B disease. These autosomal recessive disorders are caused by b-galactosidase deficiency. A hallmark of GM1 gangliosidosis is central nervous system degeneration where ganglioside synthesis is highest. The accumulation of keratan sulfate is the suspected cause of the bone findings in Morquio B disease. GM1 gangliosidosis is clinically characterized by a neurodegenerative disorder associated with dysostosis multiplex, while Morquio B disease is characterized by severe skeletal manifestations and the preservation of intelligence. Morquio B disease and GM1 gangliosidosis may be on a continuum of skeletal involvement. There is currently no effective treatment for GLB1-related disorders. Recently, multiple interventions have been developed and there are several ongoing clinical trials.
Keywords
GM1 gangliosidosis; Mucopolysaccharidoses IVB; Morquio B disease; Beta-galactosidase; GLB1;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Tomatsu S, Montano AM, Oikawa H, Smith M, Barrera L, Chinen Y, et al. Mucopolysaccharidosis type IVA (Morquio A disease): clinical review and current treatment. Curr Pharm Biotechnol 2011;12:931-45.   DOI
2 Bleier M, Yuskiv N, Priest T, Moisa Popurs MA, Stockler-Ipsiroglu S; BC Children's Hospital; University of British Columbia. Morquio B patient/caregiver survey: first insight into the natural course of a rare GLB1 related condition. Mol Genet Metab Rep 2018;16:57-63.   DOI
3 Sohn YB, Park HD, Park SW, Kim SH, Cho SY, Ko AR, et al. A Korean patient with Morquio B disease with a novel c.13_14insA mutation in the GLB1 gene. Ann Clin Lab Sci 2012;42:89-93.
4 Montano AM, Tomatsu S, Gottesman GS, Smith M, Orii T. International Morquio A Registry: clinical manifestation and natural course of Morquio A disease. J Inherit Metab Dis 2007;30:165-74.   DOI
5 Fischetto R, Palladino V, Mancardi MM, Giacomini T, Palladino S, Gaeta A, et al. Substrate reduction therapy with Miglustat in pediatric patients with GM1 type 2 gangliosidosis delays neurological involvement: a multicenter experience. Mol Genet Genomic Med 2020;8:e1371.
6 Holzgreve W, Grobe H, von Figura K, Kresse H, Beck H, Mattei JF. Morquio syndrome: clinical findings in 11 patients with MPS IVA and 2 patients with MPS IVB. Hum Genet 1981;57:360-5.   DOI
7 Mayer FQ, Pereira Fdos S, Fensom AH, Slade C, Matte U, Giugliani R. New GLB1 mutation in siblings with Morquio type B disease presenting with mental regression. Mol Genet Metab 2009;96:148.   DOI
8 Latour YL, Yoon R, Thomas SE, Grant C, Li C, Sena-Esteves M, et al. Human GLB1 knockout cerebral organoids: a model system for testing AAV9-mediated GLB1 gene therapy for reducing GM1 ganglioside storage in GM1 gangliosidosis. Mol Genet Metab Rep 2019;21:100513.   DOI
9 Front S, Almeida S, Zoete V, Charollais-Thoenig J, Gallienne E, Marmy C, et al. 4-epi-Isofagomine derivatives as pharmacological chaperones for the treatment of lysosomal diseases linked to β-galactosidase mutations: improved synthesis and biological investigations. Bioorg Med Chem 2018;26:5462-9.   DOI
10 Weismann CM, Ferreira J, Keeler AM, Su Q, Qui L, Shaffer SA, et al. Systemic AAV9 gene transfer in adult GM1 gangliosidosis mice reduces lysosomal storage in CNS and extends lifespan. Hum Mol Genet 2015;24:4353-64.   DOI
11 Acosta W, Cramer CL. Targeting macromolecules to CNS and other hard-to-treat organs using lectin-mediated delivery. Int J Mol Sci 2020;21:971.   DOI
12 Condori J, Acosta W, Ayala J, Katta V, Flory A, Martin R, et al. Enzyme replacement for GM1-gangliosidosis: uptake, lysosomal activation, and cellular disease correction using a novel β-galactosidase:RTB lectin fusion. Mol Genet Metab 2016;117:199-209.   DOI
13 Takai T, Higaki K, Aguilar-Moncayo M, Mena-Barragan T, Hirano Y, Yura K, et al. A bicyclic 1-deoxygalactonojirimycin derivative as a novel pharmacological chaperone for GM1 gangliosidosis. Mol Ther 2013;21:526-32.   DOI
14 Paschke E, Milos I, Kreimer-Erlacher H, Hoefler G, Beck M, Hoeltzenbein M, et al. Mutation analyses in 17 patients with deficiency in acid beta-galactosidase: three novel point mutations and high correlation of mutation W273L with Morquio disease type B. Hum Genet 2001;109:159-66.   DOI
15 Front S, Biela-Banas A, Burda P, Ballhausen D, Higaki K, Caciotti A, et al. (5aR)-5a-C-Pentyl-4-epi-isofagomine: a powerful inhibitor of lysosomal b-galactosidase and a remarkable chaperone for mutations associated with GM1-gangliosidosis and Morquio disease type B. Eur J Med Chem 2017;126:160-70.   DOI
16 Higaki K, Li L, Bahrudin U, Okuzawa S, Takamuram A, Yamamoto K, et al. Chemical chaperone therapy: chaperone effect on mutant enzyme and cellular pathophysiology in β-galactosidase deficiency. Hum Mutat 2011;32:843-52.   DOI
17 Mohamed FE, Al Sorkhy M, Ghattas MA, Al-Gazali L, Al-Dirbashi O, Al-Jasmi F, et al. The pharmacological chaperone N-n-butyl-deoxygalactonojirimycin enhances β-galactosidase processing and activity in fibroblasts of a patient with infantile GM1-gangliosidosis. Hum Genet 2020;139:657-73.   DOI
18 Elliot-Smith E, Speak AO, Lloyd-Evans E, Smith DA, van der Spoel AC, Jeyakumar M, et al. Beneficial effects of substrate reduction therapy in a mouse model of GM1 gangliosidosis. Mol Genet Metab 2008;94:204-11.   DOI
19 Przybilla MJ, Stewart C, Carlson TW, Ou L, Koniar BL, Sidhu R, et al. Examination of a blood-brain barrier targeting β-galactosidasemonoclonal antibody fusion protein in a murine model of GM1-gangliosidosis. Mol Genet Metab Rep 2021;27:100748.   DOI
20 Chen JC, Luu AR, Wise N, Angelis R, Agrawal V, Mangini L, et al. Intracerebroventricular enzyme replacement therapy with β-galactosidase reverses brain pathologies due to GM1 gangliosidosis in mice. J Biol Chem 2020;295:13532-55.   DOI
21 Deodato F, Procopio E, Rampazzo A, Taurisano R, Donati MA, DionisiVici C, et al. The treatment of juvenile/adult GM1-gangliosidosis with Miglustat may reverse disease progression. Metab Brain Dis 2017;32:1529-36.   DOI
22 Wraith JE. The mucopolysaccharidoses: a clinical review and guide to management. Arch Dis Child 1995;72:263-7.   DOI
23 Roze E, Paschke E, Lopez N, Eck T, Yoshida K, Maurel-Ollivier A, et al. Dystonia and Parkinsonism in GM1 type 3 gangliosidosis. Mov Disord 2005;20:1366-9.   DOI
24 Fantur KM, Wrodnigg TM, Stutz AE, Pabst BM, Paschke E. Fluorous iminoalditols act as effective pharmacological chaperones against gene products from GLB1 alleles causing GM1-gangliosidosis and Morquio B disease. J Inherit Metab Dis 2012;35:495-503.   DOI
25 Jarnes Utz JR, Kim S, King K, Ziegler R, Schema L, Redtree ES, et al. Infantile gangliosidoses: mapping a timeline of clinical changes. Mol Genet Metab 2017;121:170-9.   DOI
26 d'Azzo A, Tessitore A, Sano R. Gangliosides as apoptotic signals in ER stress response. Cell Death Differ 2006;13:404-14.   DOI
27 van der Voorn JP, Kamphorst W, van der Knaap MS, Powers JM. The leukoencephalopathy of infantile GM1 gangliosidosis: oligodendrocytic loss and axonal dysfunction. Acta Neuropathol 2004;107:539-45.   DOI
28 Brunetti-Pierri N, Scaglia F. GM1 gangliosidosis: review of clinical, molecular, and therapeutic aspects. Mol Genet Metab 2008;94:391-6.   DOI
29 Ferreira CR, Regier DS, Yoon R, Pan KS, Johnston JM, Yang S, et al. The skeletal phenotype of intermediate GM1 gangliosidosis: clinical, radiographic and densitometric features, and implications for clinical monitoring and intervention. Bone 2020;131:115142.   DOI
30 Regier DS, Tifft CJ, Rothermel CE. GLB1-related disorders. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, eds. GeneReviews®. Seattle: University of Washington, 1993.
31 Baiotto C, Sperb F, Matte U, da Silva CD, Sano R, Coelho JC, et al. Population analysis of the GLB1 gene in South Brazil. Genet Mol Biol 2011;34:45-8.   DOI
32 Lee JS, Choi JM, Lee M, Kim SY, Lee S, Lim BC, et al. Diagnostic challenge for the rare lysosomal storage disease: late infantile GM1 gangliosidosis. Brain Dev 2018;40:383-90.   DOI
33 Ou L, Kim S, Whitley CB, Jarnes-Utz JR. Genotype-phenotype correlation of gangliosidosis mutations using in silico tools and homology modeling. Mol Genet Metab Rep 2019;20:100495.   DOI
34 Baehner F, Schmiedeskamp C, Krummenauer F, Miebach E, Bajbouj M, Whybra C, et al. Cumulative incidence rates of the mucopolysaccharidoses in Germany. J Inherit Metab Dis 2005;28:1011-7.   DOI
35 Hecht JT, Scott CI Jr, Smith TK, Williams JC. Mild manifestations of the Morquio syndrome. Am J Med Genet 1984;18:369-71.   DOI
36 Simonaro CM, D'Angelo M, Haskins ME, Schuchman EH. Joint and bone disease in mucopolysaccharidoses VI and VII: identification of new therapeutic targets and biomarkers using animal models. Pediatr Res 2005;57(5 Pt 1):701-7.   DOI
37 Suzuki Y, Oshima A, Nanba E. β-Galactosidase deficiency (β-galactosidosis): GM1 gangliosidosis and Morquio B disease. In: Scriver CR, Beaudet AL, Valle D, Sly WS, eds. The metabolic and molecular bases of inherited disease. 8th ed. New York: McGraw-Hill, 2001;3775-809.
38 Caciotti A, Donati MA, Bardelli T, d'Azzo A, Massai G, Luciani L, et al. Primary and secondary elastin-binding protein defect leads to impaired elastogenesis in fibroblasts from GM1-gangliosidosis patients. Am J Pathol 2005;167:1689-98.   DOI
39 Abumansour IS, Yuskiv N, Paschke E, Stockler-Ipsiroglu S. Morquio-B disease: clinical and genetic characteristics of a distinct GLB1-related dysostosis multiplex. JIMD Rep 2019;51:30-44.   DOI
40 Tessitore A, del P Martin M, Sano R, Ma Y, Mann L, Ingrassia A, et al. GM1-ganglioside-mediated activation of the unfolded protein response causes neuronal death in a neurodegenerative gangliosidosis. Mol Cell 2004;15:753-66.   DOI
41 Suzuki Y, Nanba E, Matsuda J, Higaki K, Oshima A. β-Galactosidase deficiency (β-Galactosidosis): GM1 gangliosidosis and Morquio B disease. In: Valle DL, Beaudet AL, Vogelstein, B, Kinzler KW, Antonarakis SE, Ballabio A, et al., eds. The online metabolic and molecular bases of inherited disease. New York: McGraw-Hill, 2014.
42 Khan SA, Mason RW, Giugliani R, Orii K, Fukao T, Suzuki Y, et al. Glycosaminoglycans analysis in blood and urine of patients with mucopolysaccharidosis. Mol Genet Metab 2018;125:44-52.   DOI
43 Folkerth RD. Abnormalities of developing white matter in lysosomal storage diseases. J Neuropathol Exp Neurol 1999;58:887-902.   DOI
44 Yang CF, Wu JY, Tsai FJ. Three novel beta-galactosidase gene mutations in Han Chinese patients with GM1 gangliosidosis are correlated with disease severity. J Biomed Sci 2010;17:79.   DOI
45 Nelson J, Crowhurst J, Carey B, Greed L. Incidence of the mucopolysaccharidoses in Western Australia. Am J Med Genet A 2003;123A:310-3.   DOI
46 Stockler-Ipsiroglu S, Yazdanpanah N, Yazdanpanah M, Popurs MM, Yuskiv N, Schmitz Ferreira Santos ML, et al. Morquio-like dysostosis multiplex presenting with neuronopathic features is a distinct GLB1-related phenotype. JIMD Rep 2021, in press.
47 Beck M, Petersen EM, Spranger J, Beighton P. Morquio's disease type B (beta-galactosidase deficiency) in three siblings. S Afr Med J 1987;72:704-7.
48 Khan SA, Peracha H, Ballhausen D, Wiesbauer A, Rohrbach M, Gautschi M, et al. Epidemiology of mucopolysaccharidoses. Mol Genet Metab 2017;121:227-40.   DOI