Electron Microscopy as a Useful Tool in the Diagnosis of Lysosomal Storage Diseases

Diagnostic Electron Microscopy - A Practical Guide to Interpretation and Technique

Volumn , Issue , 2013, Pages 237-267

  Alroy, Joseph ^a,b   Pfannl, Rolf ^b   Ucci, Angelo A ^b  

^a TUFTS UNIVERSITY   (United States)

^b TUFTS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Disease onset, mutated gene nature type; EM in lysosomal storage disease diagnosis; EM, distinction of lysosomal storage disease from others; Lysosomal storage disease, and storage disease classes; Lysosomal storage diseases, and intralysosomal deficiency; Lysosomes, cell digestive recycling centre; Morphological findings; Pompe disease, glycogen storage disease type II

Indexed keywords

EID: 84886675222     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1002/9781118452813.ch8     Document Type: Chapter

References (79)

1. Aberg, L., Autti, T., Cooper, J.D. et al. (2011) CLN5, in The Neuronal Ceroid Lipofuscinoses (Batten Disease), 2nd edn (eds S. Mole, R.E. Williams and H.H. Goebel), Oxford University Press, Oxford, pp. 140-158.
2. Aiello, C., Cannelli, N., Cooper, J.D. et al. (2011) CLN8, in The Neuronal Ceroid Lipofuscinoses (Batten Disease), Oxford, 2nd edn (eds S. Mole, R.E. Williams, and H.H. Goebel), Oxford University Press, pp. 189-202.
3. Albay, D., Adler, S.G., Philipose, J. et al. (2005) Chloroquine-induced lipidosis mimicking Fabry disease. Modern Pathology, 18, 733-738.
4. Alroy, J., Braulke, T., Cismondi, I.A. et al. (2011) CLN6, in The Neuronal Ceroid Lipofuscinoses (Batten Disease), Oxford, 2nd edn (eds S. Mole, R.E. Williams, and H.H. Goebel), Oxford University Press, pp. 159-175.
5. Alroy, J., Pfannl, R., Slavov, D. and Taylor, M.R. (2010) Electron microscopic findings in skin biopsies from patients with Danon disease. Ultrastructural Pathology, 34, 333-336.
6. Alroy, J., Pfannl, R., Ucci, A. et al. (2007) Electron microscopic findings in skin biopsies from patients with infantile osteopetrosis and neuronal storage disease. Ultrastructural Pathology, 31, 333-338.
7. Alroy, J. and Ucci, A.A. (2006) Skin biopsy: a useful tool in the diagnosis of lysosomal storage diseases. Ultrastructural Pathology, 30, 489-503.
8. Alroy, J., Ucci, A.A. and Pfannl, R. (2006) Why skin biopsy is useful for the diagnosis of lysosomal storage diseases. Current Medical Literature, 5, 70-76.
9. Ambler, M.W., Trice, J., Grauerholz, J. and O'Shea, P.A. (1983) Infantile osteopetrosis and neuronal storage disease. Neurology, 33, 437-441.
10. Aronson, N.N. Jr. (1999) Aspartylglycosaminuria: biochemistry and molecular biology. Biochimica et Biophysica Acta, 1455, 139-154.
11. Assmann, G. and Seedorf, U. (2001) Acid lipase deficiency: Wolman disease and cholesteryl ester storage disease, in The Metabolic and Molecular Basis of Inherited Disease, 8th edn (eds C. Scriver, A.L. Beaudet, W.S. Sly and D. Valle), McGraw-Hill, New York, pp. 3551-3572.
12. Aula, N., Jalanko, A., Aula, P. and Peltonen, L. (2002) Unraveling the molecular pathogenesis of free sialic acid storage disorders: altered targeting of mutant sialin. Molecular Genetics and Metabolism, 77, 99-107.
13. Autti, T., Cooper, J.D., Van Diggelen, O.P. et al. (2011) CLN1, in The Neuronal Ceroid Lipofuscinoses (Batten Disease), 2nd edn (eds S. Mole, R.E. Williams and H.H. Goebel) Oxford University Press, Oxford, pp. 55-79.
14. Avila, J.L. and Convit, J. (1975) Inhibition of leucocytic lysosomal enzymes by glycosaminoglycans in vitro. The Biochemical Journal, 152, 57-64.
15. Bakker, H.D., De Sonnaville, M.L., Vreken, P. et al. (2001) Human alpha-Nacetylgalactosaminidase (alpha-NAGA) deficiency: no association with neuroaxonal dystrophy? European Journal of Human Genetics: EJHG, 9, 91-96.
16. Beesley, C.E., Jackson, M., Young, E.P. et al. (2005) Molecular defects in Sanfilippo syndrome type B (mucopolysaccharidosis IIIB). Journal of Inherited Metabolic Disease, 28, 759-767.
17. Belcher, R.W. (1972) Ultrastructure of the skin in the genetic mucopolysaccharidoses. Archives of Pathology, 94, 511-518.
18. Bendavid, C., Kleta, R., Long, R. et al. (2004) FISH diagnosis of the common 57-kb deletion in CTNS causing cystinosis. Human Genetics, 115, 510-514.
19. Benjamin, E.R., Flanagan, J.J., Schilling, A. et al. (2009) The pharmacological chaperone 1-deoxygalactonojirimycin increases alpha-galactosidase A levels in Fabry patient cell lines. Journal of Inherited Metabolic Disease, 32, 424-440.
20. Bertola, F., Filocamo, M., Casati, G. et al. (2011) IDUA mutational profiling of a cohort of 102 European patients with mucopolysaccharidosis type I: identification and characterization of 35 novel alpha-L-iduronidase (IDUA) alleles. Human Mutation, 32, E2189-E2210.
21. Boustany, R.M., Ceuterick-De Groote, C., Goebel, H.H. et al. (2011) Genetically unassigned or unusual NCLs, in The Neuronal Ceroid Lipofuscinoses (Batten Disease), 2nd edn (eds S. Mole, R.E. Williams and H.H. Goebel), Oxford University Press, Oxford, pp. 213-236.
22. Castagnaro, M., Alroy, J., Ucci, A.A. and Glew, R.H. (1987) Lectin histochemistry and ultrastructure of feline kidneys from six different storage diseases. Virchows Archiv. B, Cell Pathology Including Molecular Pathology, 54, 16-26.
23. Cesani, M., Capotondo, A., Plati, T. et al. (2009) Characterization of new arylsulfatase A gene mutations reinforces genotype-phenotype correlation in metachromatic leukodystrophy. Human Mutation, 30, E936-E945.
24. Chabas, A., Duque, J. and Gort, L. (2007) A new infantile case of alpha-Nacetylgalactosaminidase deficiency. Cardiomyopathy as a presenting symptom. Journal of Inherited Metabolic Disease, 30, 108.
25. Chang, M., Cooper, J.D., Davidson, B.L. et al. (2011) CLN2, in The Neuronal Ceroid Lipofuscinoses (Batten Disease) (eds S. Mole, R.E. Williams and H.H. Goebel), Oxford University Press, Oxford, pp. 80-109.
26. Cooper, J.D., Partanen, S., Siintola, E. et al. (2011) CLN10, in The Neuronal Ceroid Lipofuscinoses (Batten Disease), 2nd edn (eds S. Mole, R.E. Williams and H.H. Goebel), Oxford University Press, Oxford, pp. 203-212.
27. Diaz-Font, A., Cormand, B., Santamaria, R. et al. (2005a) A mutation within the saposin D domain in a Gaucher disease patient with normal glucocerebrosidase activity. Human Genetics, 117, 275-277.
28. Diaz-Font, A., Santamaria, R., Cozar, M. et al. (2005b) Clinical and mutational characterization of three patients with multiple sulfatase deficiency: report of a new splicing mutation. Molecular Genetics and Metabolism, 86, 206-211.
29. Dvorak, A.M., Cable, W.J., Osage, J.E. and Kolodny, E.H. (1981) Diagnostic electron microscopy. II. Fabry's disease: use of biopsies from uninvolved skin. Acute and chronic changes involving the microvasculature and small unmyelinated nerves. Pathology Annual, 16 (Pt 1), 139-158.
30. Elleder, M., Kousi, M., Lehesjoki, A.E. et al. (2011) CLN7, in The Neuronal Ceroid Lipofuscinoses (Batten Disease), 2nd edn (eds S. Mole, R.E. Williams and H.H. Goebel), Oxford University Press, Oxford, pp. 176-188.
31. Feldhammer, M., Durand, S., Mrazova, L. et al. (2009) Sanfilippo syndrome type C: mutation spectrum in the heparan sulfate acetyl-CoA: alpha-glucosaminide N-acetyltransferase (HGSNAT) gene. Human Mutation, 30, 918-925.
32. Fernandez-Valero, E.M., Ballart, A., Iturriaga, C. et al. (2005) Identification of 25 new mutations in 40 unrelated Spanish Niemann-Pick type C patients: genotypephenotype correlations. Clinical Genetics, 68, 245-254.
33. Fowler, D.J., Anderson, G., Vellodi, A. et al. (2007) Electron microscopy of chorionic villus samples for prenatal diagnosis of lysosomal storage disorders. Ultrastructural Pathology, 31, 15-21.
34. Gahl, W.A., Thoene, J.G. and Schneider, J.A. (2001) Cystinosis: a disorder of lysosomal membrane transport, in The Metabolic and Molecular Basis of Inherited Disease, 8th edn (eds C. Scriver, A.L. Beaudet, W.S. Sly and D. Valle), McGraw-Hill, New York, pp. 5085-5108.
35. Gelb, B.D., Bromme, D. and Desnick, R.J. (2001) Pycnodysostosis: cathepsin K deficiency, in The Metabolic and Molecular Basis of Inherited Disease, 8th edn (eds C. Scriver, A.L. Beaudet, W.S. Sly and D. Valle), McGraw-Hill, New York, pp. 4244-4261.
36. Gherardi, R.K., Coquet, M., Cherin, P. et al. (2001) Macrophagic myofasciitis lesions assess long-term persistence of vaccine-derived aluminium hydroxide in muscle. Brain, 124, 1821-1831.
37. Gucev, Z.S., Tasic, V., Jancevska, A. et al. (2008) Novel beta-galactosidase gene mutation p.W273R in a woman with mucopolysaccharidosis type IVB (Morquio B) and lack of response to in vitro chaperone treatment of her skin fibroblasts. American Journal of Medical Genetics. Part A, 146A, 1736-1740.
38. Hammel, I. and Alroy, J. (1995) The effect of lysosomal storage diseases on secretory cells: an ultrastructural study of pancreas as an example. Journal of Submicroscopic Cytology and Pathology, 27, 143-160.
39. Hammel, I., Alroy, J., Goyal, V. and Galli, S.J. (1993) Ultrastructure of human dermal mast cells in 29 different lysosomal storage diseases. Virchows Archiv. B, Cell Pathology Including Molecular Pathology, 64, 83-89.
40. Hirschhorn, R. and Reuser, A. (2001) Glycogen storage disease type II: acid α-glucosidase (acid maltase) deficiency, in The Metabolic and Molecular Basis of Inherited Disease, 8th edn (eds C. Scriver, A.L. Beaudet, W.S. Sly and D. Valle), McGraw-Hill, New York, pp. 3389-3420.
41. Holbrook, K.A. and Byers, P.H. (1989) Skin is a window on heritable disorders of connective tissue. American Journal of Medical Genetics, 34, 105-121.
42. Hruban, Z. (1984) Pulmonary and generalized lysosomal storage induced by amphiphilic drugs. Environmental Health Perspectives, 55, 53-76.
43. Isenberg, J.N. and Sharp, H.L. (1976) Aspartylglucosaminuria: unique biochemical and ultrastructural characteristics. Human Pathology, 7, 469-481.
44. Jalanko, A. and Braulke, T. (2009) Neuronal ceroid lipofuscinoses. Biochimica et Biophysica Acta, 1793, 697-709.
45. Karageorgos, L., Brooks, D.A., Pollard, A. et al. (2007) Mutational analysis of 105 mucopolysaccharidosis type VI patients. Human Mutation, 28, 897-903.
46. Khan, B., Ahmed, Z. and Ahmad, W. (2010) A novel missense mutation in cathepsin K (CTSK) gene in a consanguineous Pakistani family with pycnodysostosis. Journal of Investigative Medicine, 58, 720-724.
47. Kuchar, L., Ledvinova, J., Hrebicek, M. et al. (2009) Prosaposin deficiency and saposin B deficiency (activator-deficient metachromatic leukodystrophy): report on two patients detected by analysis of urinary sphingolipids and carrying novel PSAP gene mutations. American Journal of Medical Genetics, Part A, 149A, 613-621.
48. Lin, S.P., Chang, J.H., De La Cadena, M.P. et al. (2007) Mutation identification and characterization of a Taiwanese patient with fucosidosis. Journal of Human Genetics, 52, 553-556.
49. Lohse, P., Maas, S., Elleder, M. et al. (2000) Compound heterozygosity for a Wolman mutation is frequent among patients with cholesteryl ester storage disease. Journal of Lipid Research, 41, 23-31.
50. Lualdi, S., Tappino, B., Di Duca, M. et al. (2010) Enigmatic in vivo iduronate-2-sulfatase (IDS) mutant transcript correction to wild-type in Hunter syndrome. Human Mutation, 31, E1261-E1285.
51. Malvagia, S., Morrone, A., Caciotti, A. et al. (2004) New mutations in the PPBG gene lead to loss of PPCA protein which affects the level of the beta-galactosidase/neuraminidase complex and the EBP-receptor. Molecular Genetics and Metabolism, 82, 48-55.
52. Mark, B.L., Mahuran, D.J., Cherney, M.M. et al. (2003) Crystal structure of human beta-hexosaminidase B: understanding the molecular basis of Sandhoff and Tay-Sachs disease. Journal of Molecular Biology, 327, 1093-1109.
53. Merin, S., Livni, N., Berman, E.R. and Yatziv, S. (1975) Mucolipidosis IV: ocular, systemic, and ultrastructural findings. Investigative Ophthalmology, 14, 437-448.
54. Meyer, A., Kossow, K., Gal, A. et al. (2008) The mutation p.Ser298Pro in the sulphamidase gene (SGSH) is associated with a slowly progressive clinical phenotype in mucopolysaccharidosis type IIIA (Sanfilippo A syndrome). Human Mutation, 29, 770.
55. Montano, A.M., Sukegawa, K., Kato, Z. et al. (2007) Effect of 'attenuated' mutations in mucopolysaccharidosis IVA on molecular phenotypes of Nacetylgalactosamine-6-sulfate sulfatase. Journal of Inherited Metabolic Disease, 30, 758-767.
56. Ono, S., Waring, S.C., Kurland, L.L. et al. (1997) Guamanian neurodegenerative disease: ultrastructural studies of skin. Journal of the Neurological Sciences, 146, 35-40.
57. Pangrazio, A., Pusch, M., Caldana, E. et al. (2010) Molecular and clinical heterogeneity in CLCN7-dependent osteopetrosis: report of 20 novel mutations. Human Mutation, 31, E1071-E1080.
58. Park, Y.E., Park, K.H., Lee, C.H. et al. (2006) Two new missense mutations of GAA in late onset glycogen storage disease type II. Journal of the Neurological Sciences, 251, 113-117.
59. Park, J.H. and Schuchman, E.H. (2006) Acid ceramidase and human disease. Biochimica et Biophysica Acta, 1758, 2133-2138.
60. Pattison, S., Pankarican, M., Rupar, C.A. et al. (2004) Five novel mutations in the lysosomal sialidase gene (NEU1) in type II sialidosis patients and assessment of their impact on enzyme activity and intracellular targeting using adenovirusmediated expression. Human Mutation, 23, 32-39.
61. Prasad, A., Kaye, E.M. and Alroy, J. (1996) Electron microscopic examination of skin biopsy as a cost-effective tool in the diagnosis of lysosomal storage diseases. Journal of Child Neurology, 11, 301-308.
62. Riise Stensland, H.M., Klenow, H.B., Van Nguyen, L. et al. (2012) Identification of 83 novel alpha-mannosidosis-associated sequence variants: functional analysis of MAN2B1 missense mutations. Human Mutation, 33, 511-520.
63. Riise Stensland, H.M., Persichetti, E., Sorriso, C. et al. (2008) Identification of two novel beta-mannosidosis-associated sequence variants: biochemical analysis of beta-mannosidase (MANBA) missense mutations. Molecular Genetics and Metabolism, 94, 476-480.
64. Rodriguez-Pascau, L., Gort, L., Schuchman, E.H. et al. (2009) Identification and characterization of SMPD1 mutations causing Niemann-Pick types A and B in Spanish patients. Human Mutation, 30, 1117-1122.
65. Ruchoux, M.M. and Maurage, C.A. (1998) Endothelial changes in muscle and skin biopsies in patients with CADASIL. Neuropathology and Applied Neurobiology, 24, 60-65.
66. Santamaria, R., Blanco, M., Chabas, A. et al. (2007) Identification of 14 novel GLB1 mutations, including five deletions, in 19 patients with GM1 gangliosidosis from South America. Clinical Genetics, 71, 273-279.
67. Spiegel, R., Bach, G., Sury, V. et al. (2005) A mutation in the saposin A coding region of the prosaposin gene in an infant presenting as Krabbe disease: first report of saposin A deficiency in humans. Molecular Genetics and Metabolism, 84, 160-166.
68. Sun, Y., Quinn, B., Xu, Y.H. et al. (2006) Conditional expression of human acid beta-glucosidase improves the visceral phenotype in a Gaucher disease mouse model. Journal of Lipid Research, 47, 2161-2170.
69. Takahashi, K., Naito, M., Yamamura, F. et al. (1990) Infantile osteopetrosis complicating neuronal ceroid lipofuscinosis. Pathology, Research and Practice, 186, 697-706.
70. Tappino, B., Regis, S., Corsolini, F. and Filocamo, M. (2008) An Alu insertion in compound heterozygosity with a microduplication in GNPTAB gene underlies mucolipidosis II. Molecular Genetics and Metabolism, 93, 129-133.
71. Tomatsu, S., Montano, A.M., Dung, V.C. et al. (2009) Mutations and polymorphisms in GUSB gene in mucopolysaccharidosis VII (Sly syndrome). Human Mutation, 30, 511-519.
72. Triggs-Raine, B., Salo, T.J., Zhang, H. et al. (1999) Mutations in HYAL1, a member of a tandemly distributed multigene family encoding disparate hyaluronidase activities, cause a newly described lysosomal disorder, mucopolysaccharidosis IX. Proceedings of the National Academy of Sciences of the United States of America, 96, 6296-6300.
73. Tunon, T., Guerrero, D., Urchaga, A. et al. (2008) Danon disease: a novel LAMP-2 gene mutation in a family with four affected members. Neuromuscular Disorders, 18, 167-174.
74. Tylki-Szymanska, A., Czartoryska, B., Vanier, M.T. et al. (2007) Nonneuronopathic Gaucher disease due to saposin C deficiency. Clinical Genetics, 72, 538-542.
75. Ushiyama, M., Ikeda, S., Nakayama, J. et al. (1985) Type III (chronic) GM1-gangliosidosis. Histochemical and ultrastructural studies of rectal biopsy. Journal of the Neurological Sciences, 71, 209-223.
76. Valstar, M.J., Bertoli-Avella, A.M., Wessels, M.W. et al. (2010) Mucopolysaccharidosis type IIID: 12 new patients and 15 novel mutations. Human Mutation, 31, E1348-E1360.
77. Verot, L., Chikh, K., Freydiere, E. et al. (2007) Niemann-Pick C disease: functional characterization of three NPC2 mutations and clinical and molecular update on patients with NPC2. Clinical Genetics, 71, 320-330.
78. Vracko, R. and Benditt, E.P. (1974) Manifestations of diabetes mellitus-their possible relationships to an underlying cell defect. A review. American Journal of Pathology, 75, 204-224.
79. Zeevi, D.A., Frumkin, A. and Bach, G. (2007) TRPML and lysosomal function. Biochimica et Biophysica Acta, 1772, 851-858.