J Pediatr Genet 2019; 08(04): 198-204
DOI: 10.1055/s-0039-1697605
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Clinical Characterization of Mucolipidoses II and III: A Multicenter Study

Taciane Alegra
1   Postgraduate Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
,
Fernanda Sperb-Ludwig
1   Postgraduate Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
2   BRAIN Laboratory, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
,
Nicole Ruas Guarany
3   Occupational Therapy Faculty, Federal University of Pelotas, Pelotas, Brazil
,
Erlane M. Ribeiro
4   Hospital Infantil Albert Sabin, Fortaleza, Brazil
,
Charles M. Lourenço
5   Ribeirão Preto Clinics Hospital, Universidade de São Paulo, Ribeirão Preto, Brazil
,
Chong Ae Kim
6   Genetics Unit, Instituto da Criança, School of Medicine, Universidade de São Paulo, São Paulo, Brazil
,
Eugênia R. Valadares
7   Department of Complementary Propaedeutics, Faculty of Medicine, Federal University of Minas Gerais (UFMG), Belo Horizonte, Brazil
,
Marcial Francis Galera
8   Department of Pediatrics, School of Medicine, Federal University of Mato Grosso, Cuiabá, Brazil
,
Angelina X. Acosta
9   Faculdade de Medicina, Departamento de Pediatria, Setor de Genética, Universidade Federal da Bahia, Salvador, Brazil
,
Dafne Dain Gandelman Horovitz
10   Department of Genetics, Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira, Fiocruz, Rio de Janeiro, Brazil
,
Ida Vanessa Doederlein Schwartz
1   Postgraduate Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
11   Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
12   Department of Genetics, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
› Author Affiliations
Funding Financial support for this project was provided by FIPE-HCPA, FAPERGS, CAPES, CNPq (Brazil), and the UFRGS Graduate Program in Genetics and Molecular Biology.
Further Information

Publication History

19 March 2019

15 August 2019

Publication Date:
24 September 2019 (online)

Abstract

Mucolipidoses (MLs) II and III are rare lysosomal diseases caused by deficiency of GlcNAc-1-phosphotransferase, and clinical manifestations are multisystemic. Clinical and demographic data from 1983 to 2013 were obtained retrospectively. Twenty-seven patients were included (ML II = 15, ML III α/beta = 9, ML III gamma = 3). The median age at diagnosis was 2.7 years. The predominant clinical presentations were skeletal symptoms. The ML II patients showed physical and cognitive impairment, while the ML III α/beta patients have more somatic abnormalities and usually were delayed in early development as compared with ML III gamma patients. This is the most comprehensive study exploring characteristics of Brazilian patients with MLs II and III.

Ethical Approval

This study was approved by the Research Ethics Committee of Hospital de Clínicas de Porto Alegre (project no. 14–0257), and all patients provided written informed consent for participation.


 
  • References

  • 1 Hasilik A, Von Figura K. Oligosaccharides in lysosomal enzymes. Distribution of high-mannose and complex oligosaccharides in cathepsin D and beta-hexosaminidase. Eur J Biochem 1981; 121 (01) 125-129
  • 2 Reitman ML, Varki A, Kornfeld S. Fibroblasts from patients with I-cell disease and pseudo-Hurler polydystrophy are deficient in uridine 5′-diphosphate-N-acetylglucosamine: glycoprotein N-acetylglucosaminylphosphotransferase activity. J Clin Invest 1981; 67 (05) 1574-1579
  • 3 Hasilik A, Neufeld EF. Biosynthesis of lysosomal enzymes in fibroblasts. Synthesis as precursors of higher molecular weight. J Biol Chem 1980; 255 (10) 4937-4945
  • 4 Kornfeld S, Sly W. I-cell disease and pseudo-Hurler polydystrophy: disorders of lysosomal enzyme phosphorylation and localization. In: Valle D, Beaudet AL, Vogelstein B. , et al, eds. The Metabolic and Molecular Bases of Inherited Disease. Chap 138. New York: McGraw-Hill; 2010
  • 5 Braulke T, Bonifacino JS. Sorting of lysosomal proteins. Biochim Biophys Acta 2009; 1793 (04) 605-614
  • 6 Pinto R, Caseiro C, Lemos M. , et al. Prevalence of lysosomal storage diseases in Portugal. Eur J Hum Genet 2004; 12 (02) 87-92
  • 7 Okada S, Owada M, Sakiyama T, Yutaka T, Ogawa M. I-cell disease: clinical studies of 21 Japanese cases. Clin Genet 1985; 28 (03) 207-215
  • 8 Meikle PJ, Hopwood JJ, Clague AE, Carey WF. Prevalence of lysosomal storage disorders. JAMA 1999; 281 (03) 249-254
  • 9 Poorthuis BJ, Wevers RA, Kleijer WJ. , et al. The frequency of lysosomal storage diseases in The Netherlands. Hum Genet 1999; 105 (1-2): 151-156
  • 10 Leroy JG, Cathey S, Friez MJ. Mucolipidosis II. In: Pagon RA, Bird TC, Dolan CR. , et al, eds. GeneReviews. Seattle, WA: University of Washington; 2012
  • 11 Leroy JG, Cathey S, Friez MJ. Mucolipidosis III alpha/beta. In: Pagon RA, Bird TC, Dolan CR, Stephens K. , eds. GeneReviews. Seattle (WA): University of Washington; 2012
  • 12 Cathey SS, Kudo M, Tiede S. , et al. Molecular order in mucolipidosis II and III nomenclature. Am J Med Genet A 2008; 146A (04) 512-513
  • 13 Cathey SS, Leroy JG, Wood T. , et al. Phenotype and genotype in mucolipidoses II and III alpha/beta: a study of 61 probands. J Med Genet 2010; 47 (01) 38-48
  • 14 Raas-Rothschild A, Spiegel R. Mucolipidosis III gamma. In: Pagon RA, Bird TC, Dolan CR. , et al, eds. GeneReviews. Seattle (WA): University of Washington; 2010
  • 15 Oussoren E, van Eerd D, Murphy E. , et al. Mucolipidosis type III, a series of adult patients. J Inherit Metab Dis 2018; 41 (05) 839-848
  • 16 Cury GK, Matte U, Artigalás O. , et al. Mucolipidosis II and III alpha/beta in Brazil: analysis of the GNPTAB gene. Gene 2013; 524 (01) 59-64
  • 17 Alegra T, Cury G, Todeschini LA, Schwartz IV. Should neonatal hyperparathyroidism associated with mucolipidosis II/III be treated pharmacologically?. J Pediatr Endocrinol Metab 2013; 26 (9-10): 1011-1013
  • 18 Ceroni JRM, Spolador GM, Bermeo DS. , et al. Clinical and radiological findings in Brazilian patients with mucolipidosis types II/III. Skeletal Radiol 2019; 48 (08) 1201-1207
  • 19 Kasapkara ÇS, Akçaboy M, Kara Eroğlu F, Derinkuyu BE. Mucolipidosis type III: a rare disease in differential diagnosis of joint stiffness in pediatric rheumatology. Arch Rheumatol 2017; 33 (01) 93-98
  • 20 Alegra T, Koppe T, Acosta A. , et al. Pitfalls in the prenatal diagnosis of mucolipidosis II alpha/beta: a case report. Meta Gene 2014; 2: 403-406
  • 21 Sperb-Ludwig F, Alegra T, Voltolini R. , et al. Exome sequencing for mucolipidosis III: detection of a novel GNPTAB gene mutation in a patient with a very mild phenotype. Mol Genet Metab Rep 2014; 2: 34-37
  • 22 McElligott F, Beatty E, O'Sullivan S. , et al. Incidence of I-cell disease (mucolipidosis type II) in the Irish population. J Inherit Metab Dis 2011; 34 (03) S206
  • 23 Liu S, Zhang W, Shi H, Yao F, Wei M, Qiu Z. Mutation analysis of 16 mucolipidosis II and III alpha/beta Chinese children revealed genotype-phenotype correlations. PLoS One 2016; 11 (09) e0163204
  • 24 Nampoothiri S, Elcioglu NH, Koca SS. , et al; Mohandas Nair K. Does the clinical phenotype of mucolipidosis-IIIγ differ from its αβ counterpart?: supporting facts in a cohort of 18 patients. Clin Dysmorphol 2019; 28 (01) 7-16
  • 25 Yang M, Cho SY, Park HD. , et al. Clinical, biochemical and molecular characterization of Korean patients with mucolipidosis II/III and successful prenatal diagnosis. Orphanet J Rare Dis 2017; 12 (01) 11
  • 26 Tüysüz B, Kasapçopur Ö, Alkaya DU, Şahin S, Sözeri B, Yeşil G. Mucolipidosis type III gamma: three novel mutation and genotype-phenotype study in eleven patients. Gene 2018; 642: 398-407
  • 27 Velho RV, Alegra T, Sperb F. , et al. A de novo or germline mutation in a family with Mucolipidosis III gamma: implications for molecular diagnosis and genetic counseling. Mol Genet Metab Rep 2014; 1 (01) 98-102
  • 28 Velho RV, Ludwig NF, Alegra T. , et al. Enigmatic in vivo GlcNAc-1-phosphotransferase (GNPTG) transcript correction to wild type in two mucolipidosis III gamma siblings homozygous for nonsense mutations. J Hum Genet 2016; 61 (06) 555-560