Advanced Search
Korean J Pediatr 2012 November;55(11) :438-444.
Published online 2012 July 19.        doi:
A case of mucolipidosis II presenting with prenatal skeletal dysplasia and severe secondary hyperparathyroidism at birth
Ju Sun Heo (Heo JS), Ka Young Choi (Choi KY), Se Hyoung Sohn (Sohn SH), Curie Kim (Kim CK), Yoon Joo Kim (Kim YJ), Seung Han Shin (Shin SH), Jae Myung Lee (Lee JM), Juyoung Lee (Lee JY), Jin A Sohn (Sohn JA), Byung Chan Lim (Lim BC), Jin A Le (Le JA), Chang Won Choi (Choi CW), Ee-Kyung Kim (Kim EK), Han-Suk Kim (Kim HS), Beyong Il Kim (Kim BI), Jung-Hwan Choi (Choi JH)
Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea
Corresponding Author: Han-Suk Kim ,Tel: 02-2072-1696, Fax: 02-747-5130, Email:
Copyright © 2012 by The Korean Pediatric Society
Mucolipidosis II (ML II) or inclusion cell disease (I-cell disease) is a rarely occurring autosomal recessive lysosomal enzyme-targeting disease. This disease is usually found to occur in individuals aged between 6 and 12 months, with a clinical phenotype resembling that of Hurler syndrome and radiological findings resembling those of dysostosis multiplex. However, we encountered a rare case of an infant with ML II who presented with prenatal skeletal dysplasia and typical clinical features of severe secondary hyperparathyroidism at birth. A female infant was born at 37+1 weeks of gestation with a birth weight of 1,690 g (<3rd percentile). Prenatal ultrasonographic findings revealed intrauterine growth retardation and skeletal dysplasia. At birth, the patient had characteristic features of ML II, and skeletal radiographs revealed dysostosis multiplex, similar to rickets. In addition, the patient had high levels of alkaline phosphatase and parathyroid hormone, consistent with severe secondary neonatal hyperparathyroidism. The activities of -D-hexosaminidase and -N-acetylglucosaminidase were moderately decreased in the leukocytes but were 5- to 10-fold higher in the plasma. Examination of a placental biopsy specimen showed foamy vacuolar changes in trophoblasts and syncytiotrophoblasts. The diagnosis of ML II was confirmed via GNPTAB genetic testing, which revealed compound heterozygosity of c.3091C>T (p.Arg1031X) and c.3456_3459dupCAAC (p.Ile1154GlnfsX3), the latter being a novel mutation. The infant was treated with vitamin D supplements but expired because of asphyxia at the age of 2 months.
Keywords: Mucolipidosis II | Newborn | Newborn infant | Secondary hyperparathyroidism | Enzyme assays | Newborn infant | Secondary hyperparathyroidism
1. Hasilik A, Waheed A, von Figura K. Enzymatic phosphorylation of lysosomal enzymes in the presence of UDP-N-acetylglucosamine. Absence of the activity in I-cell fibroblasts. Biochem Biophys Res Commun 1981;98:761–767.
2. Pohl S, Marschner K, Storch S, Braulke T. Glycosylation- and phosphorylation-dependent intracellular transport of lysosomal hydrolases. Biol Chem 2009;390:521–527.
3. Cathey SS, Leroy JG, Wood T, Eaves K, Simensen RJ, Kudo M, et al. Phenotype and genotype in mucolipidoses II and III alpha/beta: a study of 61 probands. J Med Genet 2010;47:38–48.
4. Kollmann K, Pohl S, Marschner K, Encarnacao M, Sakwa I, Tiede S, et al. Mannose phosphorylation in health and disease. Eur J Cell Biol 2010;89:117–123.
5. Hickman S, Neufeld EF. A hypothesis for I-cell disease: defective hydrolases that do not enter lysosomes. Biochem Biophys Res Commun 1972;49:992–999.
6. Natowicz MR, Chi MM, Lowry OH, Sly WS. Enzymatic identification of mannose 6-phosphate on the recognition marker for receptor-mediated pinocytosis of beta-glucuronidase by human fibroblasts. Proc Natl Acad Sci U S A 1979;76:4322–432
7. Bach G, Bargal R, Cantz M. I-cell disease: deficiency of extracellular hydrolase phosphorylation. Biochem Biophys Res Commun 1979;91:976–981.
8. Hasilik A, Klein U, Waheed A, Strecker G, von Figura K. Phosphorylated oligosaccharides in lysosomal enzymes: identification of alpha-N-acetylglucosamine(1)phospho(6)mannose diester groups. Proc Natl Acad Sci U S A 1980;77:7074–707
9. Varki A, Kornfeld S. Structural studies of phosphorylated high mannose-type oligosaccharides. J Biol Chem 1980;255:10847–10858.
10. Reitman ML, Kornfeld S. UDP-N-acetylglucosamine:glycoprotein N-acetylglucosamine-1-phosphotransferase. Proposed enzyme for the phosphorylation of the high mannose oligosaccharide units of lysosomal enzymes. J Biol Chem 1981;256:4275–4281.
11. Lightbody J, Wiesmann U, Hadorn B, Herschkowitz N. I-cell disease: multiple lysosomal-enzyme defect. Lancet 1971;1:451.
12. Leroy JG, Spranger JW, Feingold M, Opitz JM, Crocker AC. I-cell disease: a clinical picture. J Pediatr 1971;79:360–365.
13. Leroy JG, Demars RI. Mutant enzymatic and cytological phenotypes in cultured human fibroblasts. Science 1967;157:804–806.
14. Hanai J, Leroy J, O'Brien JS. Ultrastructure of cultured fibroblasts in I-cell disease. Am J Dis Child 1971;122:34–38.
15. Tondeur M, Vamos-Hurwitz E, Mockel-Pohl S, Dereume JP, Cremer N, Loeb H. Clinical, biochemical, and ultrastructural studies in a case of chondrodystrophy presenting the I-cell phenotype in tissue culture. J Pediatr 1971;79:366–378.
16. Okada S, Owada M, Sakiyama T, Yutaka T, Ogawa M. I-cell disease: clinical studies of 21 Japanese cases. Clin Genet 1985;28:207–215.
17. Varki A, Reitman ML, Vannier A, Kornfeld S, Grubb JH, Sly WS. Demonstration of the heterozygous state for I-cell disease and pseudo-Hurler polydystrophy by assay of N-acetylglucosaminylphosphotransferase in white blood cells and fibroblasts. Am J Hum Genet 1982;34:717–729.
18. Unger S, Paul DA, Nino MC, McKay CP, Miller S, Sochett E, et al. Mucolipidosis II presenting as severe neonatal hyperparathyroidism. Eur J Pediatr 2005;164:236–243.
19. Kudo M, Brem MS, Canfield WM. Mucolipidosis II (I-cell disease) and mucolipidosis IIIA (classical pseudo-hurler polydystrophy) are caused by mutations in the GlcNAc-phosphotransferase alpha / beta -subunits precursor gene. Am J Hum Genet 2006;78:451–463.
20. Muller-Loennies S, Galliciotti G, Kollmann K, Glatzel M, Braulke T. A novel single-chain antibody fragment for detection of mannose 6-phosphate-containing proteins: application in mucolipidosis type II patients and mice. Am J Pathol 2010;177:240–247.
21. Taber P, Gyepes MT, Philippart M, Ling S. Roentgenographic manifestations of Leroy's I-cell disease. Am J Roentgenol Radium Ther Nucl Med 1973;118:213–2
22. Patriquin HB, Kaplan P, Kind HP, Giedion A. Neonatal mucolipidosis II (I-cell disease): clinical and radiologic features in three cases. AJR Am J Roentgenol 1977;129:37–43.
23. Pinto R, Caseiro C, Lemos M, Lopes L, Fontes A, Ribeiro H, et al. Prevalence of lysosomal storage diseases in Portugal. Eur J Hum Genet 2004;12:87–92.
24. Poorthuis BJ, Wevers RA, Kleijer WJ, Groener JE, de Jong JG, van Weely S, et al. The frequency of lysosomal storage diseases in The Netherlands. Hum Genet 1999;105:151–156.
25. Lee HJ. Inborn errors of metabolism in Korea. J Korean Neurol Assoc 2004;22:1–10.
26. Paik KH, Song SM, Ki CS, Yu HW, Kim JS, Min KH, et al. Identification of mutations in the GNPTA (MGC4170) gene coding for GlcNAc-phosphotransferase alpha/beta subunits in Korean patients with mucolipidosis type II or type IIIA. Hum Mutat 2005;26:308–314.
27. Song J, Lee DS, Cho HI, Kim JQ, Cho TJ. Biochemical characteristics of a Korean patient with mucolipidosis III (pseudo-Hurler polydystrophy). J Korean Med Sci 2003;18:722–726.
28. Saul RA, Proud V, Taylor HA, Leroy JG, Spranger J. Prenatal mucolipidosis type II (I-cell disease) can present as Pacman dysplasia. Am J Med Genet A 2005;135:328–332.
29. Lachman RS. Fetal imaging in the skeletal dysplasias: overview and experience. Pediatr Radiol 1994;24:413–417.
30. Tiede S, Storch S, Lubke T, Henrissat B, Bargal R, Raas-Rothschild A, et al. Mucolipidosis II is caused by mutations in GNPTA encoding the alpha/beta GlcNAc-1-phosphotransferase. Nat Med 2005;11:1109–1112.
PDF Links  PDF Links
Full text via DOI  Full text via DOI
  via Pubmed
Full text via PMC  Full text via PMC
via Pubreader  via PubReader
Download Citation  Download Citation
Supplementary Material  Supplementary Material
Register for e-submission
Register here to access the e-submission system of Korean J Pediatr for authors and reviewers.
Manuscript Submission
To submit a manuscript, please visit the Korean J Pediatr e-submission management system at, read the Instructions for Authors, and log into the Korean J Pediatr e-submission system. For assistance with manuscript submission, please contact:
Free archive
Anyone may access any past or current articles without logging in.
Korean Pediatric Society Office
#1606, Seocho World Officetel, 19 Seoun-ro, Seocho-gu, Seoul 137-070, Korea
TEL : +82-2-3473-7305    FAX : +82-2-3473-7307   E-mail:
BrowseCurrent IssueFor Authors and ReviewersAbout
Copyright© The Korean Pediatric Society. All right reserved.