Journal of Inherited Metabolic Disease

, Volume 33, Issue 4, pp 315–329 | Cite as

Clinical aspects of neuropathic lysosomal storage disorders

  • Laura Bannach Jardim
  • Maria Mercedes Villanueva
  • Carolina F. Moura de Souza
  • Cristina B. Oliveira Netto
LSDs with Neurologic Involvement

Abstract

The purpose of this review is to describe neurological phenotypes associated with lysosomal storage diseases (LSDs), focusing on features arising from primary neuronal involvement. Clinical presentation, progression and genetic data, are discussed in detail in Part 2, the electronic material. Main features are summarized in Part 1. Insights gained from several observational studies are discussed. Prospective studies of the natural history of most neuronopathic LSDs have been hampered by the rarity of these conditions and the short survival of affected patients. Increasingly, longitudinal observations relating to neurological manifestations are being reported. Better clinical studies are necessary, including repeated measurements of disease progression to facilitate the development of sensitive scoring systems and appropriate counseling of affected individuals and their families. Ideally, clinical studies should involve a large cohort. As treatment becomes available, knowledge of disease expression and factors that influence the phenotype may enable critical assessment of therapeutic outcomes. It is hoped that increased familiarity with the clinical expression of individual LSDs will allow early diagnosis, so families at risk are given options to consider during future pregnancies. Early diagnosis also permits the introduction of timely intervention, to favoring improved outcome in cases that are potentially treatable.

Notes

Acknowledgements

We are indebted to the patients and their families who made this study possible. We also thank Dr. Roberto Giugliani and Dr. Leonardo Vedolin for MRI and patient pictures, and Dr. Gregory Pastores for critical reading of the manuscript. This work was supported by Brazilian funding agencies (CAPES, FAPERGS, FIPE-HCPA, CNPq). Prof. Jardim is supported by CNPq.

Competing interest

None declared. As this is a review article, ethics approval was not required.

Supplementary material

10545_2010_9079_MOESM1_ESM.doc (610 kb)
ESM 1 (DOC 609 kb)
10545_2010_9079_MOESM2_ESM.jpg (1006 kb)
Fig. E-1 A cherry-red spot in the macula (GM2 gangliosidosis, Tay-Sachs disease) (JPEG 1005 kb)
10545_2010_9079_MOESM3_ESM.jpg (48 kb)
Fig. E-2 GM1 gangliosidosis patient showing a macroglossia, hypertelorism, epicanthus and coarse facial features; and b lumbar kyphosis due to dysplastic vertebrae (JPEG 48 kb)
10545_2010_9079_MOESM4_ESM.jpg (43 kb)
Fig. E-3 Some magnetic resonance imaging (MRI) patterns found in patients with lysosomal storage disorders. a Hypointense thalami and diffuse white-matter (WM) abnormality in a patient with GM1 gangliosidosis. b WM abnormalities affecting the occipital, periventricular, and central WM and sparing U fibers in a patient with the juvenile form of metachromatic leukodystrophy (MLD). c Global atrophy and high signal intensity on occipital periventricular WM in an infantile patient with Krabbe disease. d Cerebral atrophy in a patient with infantile neuronal ceroid-lipofuscinosis (INCL) (JPEG 42 kb)

References

  1. Al Sawaf S, Mayatepek E, Hoffmann B (2008) Neurological findings in Hunter disease: pathology and possible therapeutic effects reviewed. J Inherit Metab Dis 31(4):473–480CrossRefPubMedGoogle Scholar
  2. Aldenhoven M, Boelens JJ, de Koning TJ (2008) The clinical outcome of Hurler syndrome after stem cell transplantation. Biol Blood Marrow Transplant 14(5):485–498CrossRefPubMedGoogle Scholar
  3. Altarescu G, Sun M, Moore DF et al (2002) The neurogenetics of mucolipidosis type IV. Neurology 59(3):306–313PubMedGoogle Scholar
  4. Arbour LT, Silver K, Hechtman P, Treacy EP, Coulter-Mackie MB (2000) Variable onset of metachromatic leukodystrophy in a Vietnamese family. Pediatr Neurol 23(2):173–176CrossRefPubMedGoogle Scholar
  5. Augestad LB, Flanders WD (2006) Occurrence of and mortality from childhood neuronal ceroid lipofuscinoses in Norway. J Child Neurol 21(11):917–922CrossRefPubMedGoogle Scholar
  6. Baumann N, Turpin JC, Lefevre M, Colsch B (2002) Motor and psycho-cognitive clinical types in adult metachromatic leukodystrophy: genotype/phenotype relationships? J Physiol Paris 96(3-4):301–306CrossRefPubMedGoogle Scholar
  7. Boelens JJ (2006) Trends in haematopoietic cell transplantation for inborn errors of metabolism. J Inherit Metab Dis 29:413–420CrossRefPubMedGoogle Scholar
  8. Braunlin EA, Stauffer NR, Peters CH, Bass JI, Berry JM, Hopwood JJ et al (2003) Usefulness of bone marrow transplantation in the Hurler syndrome. Am J Cardiol 92:882–886CrossRefPubMedGoogle Scholar
  9. Buccoliero R, Bodennec J, Futerman AH (2002) The role of sphingolipids in neuronal development: lessons from models of sphingolipid storage diseases. Neurochem Res 27(7–8):565–574CrossRefPubMedGoogle Scholar
  10. Clarke JT, Skomorowski MA, Chang P (1989) Marked clinical difference between two sibs affected with juvenile metachromatic leukodystrophy. Am J Med Genet 33(1):10–13CrossRefPubMedGoogle Scholar
  11. Clarke LA (2008) The mucopolysaccharidoses: a success of molecular medicine. Expert Rev Mol Med 10(e1):1–18CrossRefGoogle Scholar
  12. Cooper JD (2003) Progress towards understanding the neurobiology of Batten disease or neuronal ceroid lipofuscinosis. Curr Opin Neurol 16(2):121–128CrossRefPubMedGoogle Scholar
  13. Duffner PK, Caviness VS Jr, Erbe RW, Patterson MC, Schultz KR, Wenger DA, Whitley C (2009) The long-term outcomes of presymptomatic infants transplanted for Krabbe disease: report of the workshop held on July 11 and 12, 2008, Holiday Valley, New York. Genet Med 11(6):450–454CrossRefPubMedGoogle Scholar
  14. Eng CM, Guffon N, Wilcox WR et al (2001) Safety and efficacy of recombinant human alpha-galactosidase A-replacement therapy in Fabry's disease. N Engl J Med 345:9–16CrossRefPubMedGoogle Scholar
  15. Galjart NJ, Gillemans N, Harris A et al (1988) Expression of cDNA encoding the human “protective protein” associated with lysosomal beta-galactosidase and neuroaminidase: homology to yeast proteases. Cell 54(6):755–764CrossRefPubMedGoogle Scholar
  16. Imrie J, Vijayaraghaven S, Whitehouse C et al (2002) Niemann-Pick disease type C in adults. J Inherit Metab Dis 25(6):491–500CrossRefPubMedGoogle Scholar
  17. Jalanko A, Braulke T (2009) Neuronal ceroid lipofuscinoses. Biochim Biophys Acta 1793(4):697–709CrossRefPubMedGoogle Scholar
  18. Jeyakumar M, Dwek RA, Butters TD, Platt FM (2005) Storage solutions: treating lysosomal disorders of the brain. Nat Rev Neurosci 6(9):713–725PubMedGoogle Scholar
  19. Kaback MM (2000) Population-based genetics screening for reproductive counseling: the Tay Sachs experience. Eur J Pers 159:S192–S195Google Scholar
  20. Kachur E, Del Maestro R (2000) Mucopolysaccharidoses and spinal cord compression: case report and review of the literature with implications of bone marrow transplantation. Neurosurgery 47(1):223–228CrossRefPubMedGoogle Scholar
  21. Khanna G, Van Heest AE, Agel J et al (2007) Analysis of factors affecting development of carpal tunnel syndrome in patients with Hurler syndrome after hematopoietic cell transplantation. Bone Marrow Transplant 39:331–334CrossRefPubMedGoogle Scholar
  22. Kleijer WJ, Geilen GC, Janse HC, Van Diggelen OP, Zhou XY, Galjart H, D´Azzo A (1996) Cathepsin A deficiency in galactosialidosis: studies of patients in 16 families. Pediatr Res 39(6):1067–1071CrossRefPubMedGoogle Scholar
  23. Kohlschütter A, Schulz A (2009) Towards understanding the neuronal ceroid lipofuscinoses. Brain Dev Feb 3Google Scholar
  24. Kornfeld S, Sly WS (2001) I-cell disease an pseudo-Hurler polydystrophy: disorders of lysosomal enzyme phosporylation and localization. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic and molecular bases of inherited disease, 8th edn. McGraw-Hill, New York, pp 3469–3482Google Scholar
  25. Krivit W, Aubourg P, Shapiro E, Peters C (1999) Bone marrow transplantation for globoid cell leukodystrophy, adrenoleukodystrophy, metachromatic leukodystrophy, and Hurler syndrome. Curr Opin Hematol 6(6):377–382CrossRefPubMedGoogle Scholar
  26. Kurihara M, Kumagai K, Goto K, Imai M, Yagishita S (1992) Severe type Hunter’s syndrome. Polysomnographic and neuropathological study. Neuropediatrics 23(5):248–256CrossRefPubMedGoogle Scholar
  27. Lai SC, Chen RS, Wu Chou YH et al (2009) A longitudinal study of Taiwanese Sialidosis type 1: an insight into the concept of cherry-red spot myoclonus syndrome. Eur J Neurol 16(8):912–919CrossRefPubMedGoogle Scholar
  28. Leroy JG (2007) Oligosaccharidoses, disorders allied to the oligosaccharides; Ch 108. In: Rimoin DL, Connor JM, Pyeritz RE, Korf BR (eds) Emery and Rimoin’s principles and practice of medical genetics, 5th edn. Churchill Livingstone Elsevier, Philadelphia, pp 2413–2448Google Scholar
  29. Lim ZY, Ho AY, Abrahams S et al (2008) Sustained neurological improvement following reduced-intensity conditioning allogeneic haematopoietic stem cell transplantation for late-onset Krabbe disease. Bone Marrow Transplant 41(9):831–832CrossRefPubMedGoogle Scholar
  30. Lyon G, Kolodny EH, Pastores G (2006) Neurology of hereditary metabolic disease of children, 3rd edn. McGraw-Hill, New YorkGoogle Scholar
  31. McGovern MM, Aron A, Brodie SE, Desnick RJ, Wasserstein MP (2006) Natural history of type a Niemann-Pick disease possible endpoints for therapeutic trials. Neurology 66(2):228–232CrossRefPubMedGoogle Scholar
  32. Michalski JC, Klein A (1999) Glycoprotein lysosomal storage disorders: alpha-and beta-mannosidosis, fucosidosis and alpha-N-acetylgalacto-saminidase deficiency. Biochim Biophys Acta 1455(2–3):69–84PubMedGoogle Scholar
  33. Meyer A, Kossow K, Gal A et al (2007) Scoring evaluation of the natural course of mucopolysaccharidosis type IIIA (Sanfilippo syndrome type A). Pediatrics 120(5):e1255–e1261CrossRefPubMedGoogle Scholar
  34. Montaño AM, Tomatsu S, Gottesman GS, Smith M, Orii T (2007) International Morquio a registry: clinical manifestation and natural course of morquio a disease. J Inherit Metab Dis 30(2):165–174CrossRefPubMedGoogle Scholar
  35. Moore DF, Kaneski CR, Askari H, Schiffmann R (2007) The cerebral vasculopathy of Fabry disease. J Neurol Sci 257(1–2):258–263CrossRefPubMedGoogle Scholar
  36. Muenzer J, Wraith JE, Beck M et al (2006) A phase II/III clinical study of enzyme replacement therapy with idursulfase in mucopolysaccharidosis II (Hunter syndrome). Genet Med 8:465–473CrossRefPubMedGoogle Scholar
  37. Munoz-Rojas MV, Vieira T, Costa R et al (2008) Intrathecal enzyme replacement therapy in a patient with mucopolysaccharidosis type I and symptomatic spinal cord compression. Am J Med Genet 146A(19):2538–2544CrossRefPubMedGoogle Scholar
  38. Munoz-Rojas MV, Horovitz D, Jardim LB et al. (2010) Intrathecal administration of recombinant human N-acetylgalactosamine 4-sulfatase to a MPS VI patient with pachymeningitis cervicalis. Mol Genet Metab 99(4):346–350Google Scholar
  39. Neufeld EF, Muenzer J (2001) The mucopoysaccharidoses. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic and molecular bases of inherited disease, 8th edn. McGraw-Hill, New York, pp 3421–3452Google Scholar
  40. Nidiffer FD, Kelly TE (1983) Developmental and degenerative patterns associated with cognitive, behavioural and motor difficulties in the Sanfilippo syndrome: an epidemiological study. J Ment Defic Res 27(Pt 3):185–203PubMedGoogle Scholar
  41. Patterson MC, Vanier MT, Suzuki K et al (2001) Niemann–pick disease type C: a lipid trafficking disorder. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic and molecular bases of inherited disease. McGrawHill, New York, pp 3611–3634Google Scholar
  42. Peters C, Shapiro EG, Anderson J et al (1998) Hurler syndrome: II. outcome of HLA-genotypically identical sibling and HLA haploidentical related donor bone marrow transplantation in fifty-four children. The Storage Disease Collaborative Study Group Blood 91:2601–2608Google Scholar
  43. Peters C, Steward CG, National Marrow Donor Program; International Bone Marrow Transplant Registry; Working Party on Inborn Errors, European Bone Marrow Transplant Group (2003) Hematopoietic cell transplantation for inherited metabolic diseases: an overview of outcomes and practice guidelines. Bone Marrow Transplant 31(4):229–239CrossRefPubMedGoogle Scholar
  44. Pierson TM, Bonnemann CG, Finkel RS, Bunin N, Tennekoon GI (2008) Umbilical cord blood transplantation for juvenile metachromatic leukodystrophy. Ann Neurol 64(5):583–587CrossRefPubMedGoogle Scholar
  45. Pradhan SM, Atchaneeyasakul LO, Appukuttan B et al (2002) Electronegative electroretinogram in mucolipidosis IV. Arch Ophthalmol 120(1):45–50PubMedGoogle Scholar
  46. Rauschka H, Colsch B, Baumann N et al (2006) Late-onset metachromatic leukodystrophy: genotype strongly influences phenotype. Neurology 67(5):859–863CrossRefPubMedGoogle Scholar
  47. Reuser AJJ, Drost MR (2006) Lysosomal dysfunction, cellular pathology and clinical symptoms: basic principles. Acta Pediatrica Suppl 95(451):77–78CrossRefGoogle Scholar
  48. Ruijter GJ, Valstar MJ, Van de Kamp JM et al (2008) Clinical and genetic spectrum of Sanfilippo type C (MPS IIIC) disease in The Netherlands. Mol Genet Metab 93(2):104–111CrossRefPubMedGoogle Scholar
  49. Santavuori P, Lauronen L, Kirveskari E, Åberg L, Sainio K, Autti T (2000) Neuronal ceroid lipofuscinoses in childhood. Neurol Sci 21(3 Suppl):S35–S41PubMedGoogle Scholar
  50. Santos RP, Hoo JJ (2009) Difficulty in recognizing multiple sulfatase deficiency in an infant. Pediatrics 117(3):955–958CrossRefGoogle Scholar
  51. Scarpa et al., present issueGoogle Scholar
  52. Schiffman et al., present issueGoogle Scholar
  53. Schiffmann R, Kopp JB, Austin HA III et al (2001) Enzyme replacement therapy in Fabry disease: a randomized controlled trial. JAMA 285:2743–2749CrossRefPubMedGoogle Scholar
  54. Schiffmann R, Fitz Gibbon EJ, Harris CM et al (2008) Randomized, controlled trial of miglustat in Gaucher’s disease type 3. Ann Neurol 64(5):514–522CrossRefPubMedGoogle Scholar
  55. Sevin M, Lesca G, Baumann N, Millat G, Lyon-Caen O, Vanier MT, Sedel F (2007) The adult form of niemann-pick disease type C. Brain 130(Pt 1):120–133PubMedGoogle Scholar
  56. Shapiro BE, Pastores GM, Gianutsos J, Luzy C, Kolodny EH (2009) Miglustat in late-onset Tay-Sachs disease: a 12-month, randomized, controlled clinical study with 24 months of extended treatment. Genet Med 11(6):425–433CrossRefPubMedGoogle Scholar
  57. Souillet G, Guffon N, Maire I et al (2003) Outcome of 27 patients with Hurler's syndrome transplanted from either related or unrelated haematopoietic stem cell sources. Bone Marrow Transplant 31(12):1105–1117CrossRefPubMedGoogle Scholar
  58. Staba SL, Escolar ML, Poe M et al (2004) Cord-blood transplants from unrelated donors in patients with Hurler's syndrome. N Engl J Med 350(19):1960–1969CrossRefPubMedGoogle Scholar
  59. Steinfeld R, Heim P, Von GH et al (2002) Late infantile neuronal ceroid lipofuscinosis: quantitative description of the clinical course in patients with CLN2 mutations. Am J Med Genet 112(4):347–354CrossRefPubMedGoogle Scholar
  60. Thomas GH (2001) Disordes of glycoprotein degradation: a-Mannosidosis, b-Mannosidosis, Fucosidosis and Sialidosis. In: Scriver CR, Beaudet AC, Sly WS, Valle D (eds) The metabolic and molecular bases of inherited disease. 8th edn. McGraw-Hill, New York, pp 3507–3533Google Scholar
  61. Van de Kamp JJ, Niermeijer MF, Von Figura K, Giesberts MA (1981) Genetic heterogeneity and clinical variability in the Sanfilippo syndrome (types A, B, and C). Clin Genet 20(2):152–160PubMedCrossRefGoogle Scholar
  62. Vanhanen SL, Raininko R, Autti T, Santavuori P (1995) MRI evaluation of the brain in infantile neuronal ceroid-lipofuscinosis. Part 2: MRI findings in 21 patients. J Child Neurol 10(6):444–450CrossRefPubMedGoogle Scholar
  63. Von Figura K, Gieselmann V, Jacken J (2001) Metachromatic leukodystrophy. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic and molecular bases of inherited disease, 8th edn. McGraw-Hill Book Co, New York, pp 3695–3724Google Scholar
  64. Vougioukas VI, Berlis A, Kopp MV, Korinthenberg R, Spreer J, van Velthoven V (2001) Neurosurgical interventions in children with Maroteaux-Lamy syndrome. Case report and review of the literature. Pediatr Neurosurg 35(1):35–38CrossRefPubMedGoogle Scholar
  65. Walkley SU, Zervas M, Siegel DA, Dobrenis K (1999) Gangliosides as modulators of dendritogenesis in storage disease-affected and normal pyramidal neurons. Dev Neuropsychol 16(3):361–364CrossRefGoogle Scholar
  66. Walkley SU (2003) Neurobiology and cellular pathogenesis of glycolipid storage diseases. Philos Trans R Soc Lond B Biol Sci 358(1433):893–904CrossRefPubMedGoogle Scholar
  67. Walkley SU (2009) Pathogenic cascades in lysosomal disease-why so complex? J Inherit Metab Dis 32(2):181–189CrossRefPubMedGoogle Scholar
  68. Weinreb NJ, Charrow J, Andersson HC et al (2002) Effectiveness of enzyme replacement therapy in 1028 patients with type 1 Gaucher disease after 2 to 5 years of treatment: a report from the Gaucher Registry. Am J Med 113:112–119CrossRefPubMedGoogle Scholar
  69. Wenger DA, Suzuki K, Suzuki Y, Suzuki K (2001) Galactosylceramide lipidosis: globoid cell leukodystrophy (Krabbe disease). In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic and molecular bases of inherited disease, 8th edn. McGraw-Hill, New York, pp 3669–3693Google Scholar
  70. Worgall S, Kekatpure MV, Heier L et al (2007) Neurological deterioration in late infantile neuronal ceroid lipofuscinosis. Neurology 69(6):521–535CrossRefPubMedGoogle Scholar
  71. Wraith EJ, Hopwood JJ, Fuller M, Meikle PJ, Brooks DA (2005) Laronidase treatment of mucopolysaccharidosis I. BioDrugs 19:1–7CrossRefPubMedGoogle Scholar
  72. Wraith JE (2002) Lysosomal disorders. Semin Neonatol 7(1):75–83CrossRefPubMedGoogle Scholar
  73. Yanjanin NM, Vélez JI, Gropman A et al. (2009) Linear clinical progression, independent of age of onset, in Niemann-Pick disease, type C. Am J Med Genet B Neuropsychiatr Genet May 4Google Scholar

Copyright information

© SSIEM and Springer 2010

Authors and Affiliations

  • Laura Bannach Jardim
    • 1
    • 2
  • Maria Mercedes Villanueva
    • 2
  • Carolina F. Moura de Souza
    • 2
  • Cristina B. Oliveira Netto
    • 2
  1. 1.Department of Internal MedicineUniversidade Federal do Rio Grande do SulPorto AlegreBrazil
  2. 2.Medical Genetics ServiceHospital de Clinicas de Porto AlegrePorto AlegreBrazil

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