Hostname: page-component-76fb5796d-zzh7m Total loading time: 0 Render date: 2024-04-26T14:03:28.978Z Has data issue: false hasContentIssue false
  • English
  • Français

Phenotypic Variability of Krabbe Disease Across the Lifespan

Published online by Cambridge University Press:  23 September 2014

Pamela Liao ,
Jennifer Gelinas  and
Sandra Sirrs
Pamela Liao
Affiliation:
Department of Obstetrics & Gynaecology, University of Toronto, Toronto, Ontario
Jennifer Gelinas
Affiliation:
Division of Pediatric Neurology, Faculty of Medicine, University of British Columbia, Vancouver, British
Sandra Sirrs
Affiliation:
Adult Metabolic Diseases, University of British Columbia, Vancouver, British Columbia, Canada
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Krabbe disease (galactocerebrosidase deficiency) is an inherited leukodystrophy that results in severe neurological defects due to altered myelination. Classically, disease onset is within the first year of life. Juvenile and adult-onset cases may have less classic presentations, making diagnosis difficult and often delayed. Here, we review the literature to demonstrate the hetereogeneity of presenting symptoms across all age groups. We also discuss diagnostic approach, emphasizing variation in biochemical, functional, and genetic results among Krabbe phenotypes. Better understanding of the various Krabbe disease phenotypes is critical to facilitate timely diagnosis and appropriate treatment of this clinically heterogeneous disorder.

Résumé

RÉSUMÉ

Variabilité phénotypique dans la maladie de Krabbe au cours de la vie du patient. La maladie de Krabbe (déficit en galactocérébrosidase) est une leukodystrophie héréditaire qui donne lieu à des déficits neurologiques sévères dus à un trouble de la myélinisation. Chez les cas dont la présentation est classique, la maladie débute au cours de la première année de vie. Si la maladie commence chez un adolescent ou un adulte, le mode de présentation peut-être moins classique, ce qui rend le diagnostic difficile et souvent tardif. Nous analysons les articles traitant du sujet pour démontrer l’hétérogénéité des symptômes au moment de la première consultation et ceci dans tous les groupes d’âge. Nous discutons également de l’approche diagnostique en mettant l’emphase sur la variation des résultats biochimiques, fonctionnels et génétiques des différents phénotypes dans la maladie de Krabbe. Une meilleure compréhension des différents phénotypes est cruciale pour faciliter un diagnostic précoce et un traitement approprié de cette maladie dont le mode de présentation clinique est hétérogène.

Type
Review Article
Information
Canadian Journal of Neurological Sciences , Volume 41 , Issue 1 , January 2014 , pp. 5 - 12
Copyright
Copyright © The Canadian Journal of Neurological 2014

References

1. Wenger, DA. Krabbe disease. In: Pagon, RA, Bird, TD, Dolan, CR, editors. GeneReviews. Seattle, WA: University of Washington; 2008.Google Scholar
2. Zlotogora, J, Regev, R, Zeigler, M, Iancu, TC, Bach, G. Krabbe disease: Increased incidence in a highly inbred community. Am J Med Genet. 1985;21(4):765–70.CrossRefGoogle Scholar
3. Ropper, AH, Samuels, MA. Inherited metabolic diseases of the nervous system. In: Adam and Victor’s Principles of Neurology. 9th Edition ed. USA: McGraw Hill; 2009.Google Scholar
4. Suzuki, K. Globoid cell leukodystrophy (Krabbe’s disease): Update. J Child Neurol. 2003;18(9):595–603.Google Scholar
5. Barranger, JA, Cabrera-Salazar, MA, Matsuda, J, Suzuki, K. Krabbe disease (Globoid Cell Leukodystrophy). In: Lysosomal Storage Disorders. Springer. New York, NY, US; 2007. p. 269–83.Google Scholar
6. Wenger, DA, Suzuki, K, Suzuki, Y, Suzuki, K. Galactosylceramide lipidosis: Globoid cell leukodystrophy (Krabbe disease). In: Scriver, CR, Beaudet, AL, Sly, WS, Valle, D, Vogelstein, B, editors. Metabolic and Molecular Bases of Inherited Disease. New York, NY: McGraw-Hill; 2011.Google Scholar
7. van der Voorn, JP, Pouwels, PJ, Kamphorst, W, et al. Histopathologic correlates of radial stripes on MR images in lysosomal storage disorders. AJNR Am J Neuroradiol. 2005;26(3):442–6.Google Scholar
8. Kemper, AR, Knapp, AA, Green, NS, Comeau, AM, Metterville, DR, Perrin, JM. Weighing the evidence for newborn screening for early-infantile Krabbe disease. Genet Med. 2010;12(9):539–43.Google Scholar
9. Bajaj, NP, Waldman, A, Orrell, R, Wood, NW, Bhatia, KP. Familial adult onset of Krabbe’s disease resembling hereditary spastic paraplegia with normal neuroimaging. J Neurol Neurosurg Psychiatry. 2002;72(5):635–8.Google Scholar
10. Kolodny, EH, Raghavan, S, Krivit, W. Late-onset Krabbe disease (Globoid Cell Leukodystrophy): Clinical and biochemical features of 15 cases. Dev Neurosci. 1991;(4–5):232–9.Google Scholar
11. Hagberg, B. Krabbe’s disease: Clinical presentation of neurological variants. Neuropediatrics. 1984;15 Suppl:11–5.Google Scholar
12. Escolar, ML, Poe, MD, Martin, HR, Kurtzberg, J. A staging system for infantile Krabbe disease to predict outcome after unrelated umbilical cord blood transplantation. Pediatrics. 2006;118(3): e879–89.Google Scholar
13. Duffner, PK, Jalal, K, Carter, RL. The Hunter’s Hope Krabbe family database. Pediatr Neurol. 2009;40(1):13–18.Google Scholar
14. Siddiqi, ZA, Sanders, DB, Massey, JM. Peripheral neuropathy in Krabbe disease: Electrodiagnostic findings. Neurology. 2006;67 (2):263–7.Google Scholar
15. Korn-Lubetzki, I, Dor-Wollman, T, Soffer, D, Raas-Rothschild, A, Hurvitz, H, Nevo, Y. Early peripheral nervous system manifestations of infantile Krabbe disease. Pediatr Neurol. 2003; 28(2):115–18.Google Scholar
16. Pastores, GM. Krabbe disease: an overview. Int J Clin Pharmacol Ther. 2009;47 Suppl 1:S75–81.Google Scholar
17. Kohler, W. Leukodystrophies with late disease onset: an update. Curr Opin Neurol. 2010;23(3):234–41.Google Scholar
18. Chabali, R, Matre, WM, Greene, MK. Infant with irritability, feeding problems, and progressive developmental abnormalities presenting repeatedly to a pediatric emergency department. Pediatr Emerg Care. 1997;13(2):123–6.Google Scholar
19. Fiumara, A, Barone, R, Arena, A, et al. Krabbe leukodystrophy in a selected population with high rate of late onset forms: longer survival linked to c.121G≯A (p.Gly41Ser) mutation. Clin Genet. 2011; 80(5):452–8.Google Scholar
20. Lyon, G, Hagberg, B, Evrard, P, Allaire, C, Pavone, L, Vanier, M. Symptomatology of late onset Krabbe’s leukodystrophy: the European experience. Dev Neurosci. 1991;13(4–5):240–4.CrossRefGoogle ScholarPubMed
21. Barone, R, Bruhl, K, Stoeter, P, Fiumara, A, Pavone, L, Beck, M. Clinical and neuroradiological findings in classic infantile and late-onset globoid-cell leukodystrophy (Krabbe disease). Am J Med Genet. 1996;63(1):209–17.Google Scholar
22. Loonen, MC, Van Diggelen, OP, Janse, HC, Kleijer, WJ, Arts, WF. Late-onset globoid cell leucodystrophy (Krabbe’s disease) - Clinical and genetic delineation of two forms and their relation to the early-infantile form. Neuropediatrics. 1985;16(3):137–42.Google Scholar
23. Krivit, W. Allogeneic stem cell transplantation for the treatment of lysosomal and peroxisomal metabolic diseases. Springer Semin Immunopathol. 2004;26(1–2):119–32.CrossRefGoogle ScholarPubMed
24. Phelps, M, Aicardi, J, Vanier, MT. Late onset Krabbe’s leukodystrophy: a report of four cases. J Neurol Neurosurg Psychiatry. 1991;54(4):293–6.Google Scholar
25. Arvidsson, J, Hagberg, B, Mansson, JE, Svennerholm, L. Late onset globoid cell leukodystrophy (Krabbe’s disease)-Swedish case with 15 years of follow-up. Acta Paediatr. 1995;84(2):218–21.Google Scholar
26. Turazzini, M, Beltramello, A, Bassi, R, Del Colle, R, Silvestri, M. Adult onset Krabbe’s leukodystrophy: a report of 2 cases. Acta Neurol Scand. 1997;96(6):413–15.Google Scholar
27. Verdru, P, Lammens, M, Dom, R, Van Elsen, A, Carton, H. Globoid cell leukodystrophy: a family with both late-infantile and adult type. Neurology. 1991;41(9):1382–4.CrossRefGoogle ScholarPubMed
28. Henderson, RD, MacMillan, JC, Bradfield, JM. Adult onset Krabbe disease may mimic motor neurone disease. J Clin Neurosci. 2003;10(5):638–9.Google Scholar
29. Debs, R, Froissart, R, Aubourg, P, et al. Krabbe disease in adults: phenotypic and genotypic update from a series of 11 cases and a review. J Inherit Metab Dis. 2013 Sep;36(5):859–68. Epub 2012 Nov 30.Google Scholar
30. Sabatelli, M, Quaranta, L, Madia, F, et al. Peripheral neuropathy with hypomyelinating features in adult-onset Krabbe’s disease. Neuromuscul Disord. 2002;12(4):386–91.CrossRefGoogle ScholarPubMed
31. Grewal, RP, Petronas, N, Barton, NW. Late-onset Globoid Cell Leukodystrophy. J Neurol Neurosurg Psychiatry. 1991;54(11): 1011–12.Google Scholar
32. Lim, ZY, Ho, AY, Abrahams, S, et al. Sustained neurological improvement following reduced-intensity conditioning allogeneic haematopoietic stem cell transplantation for late-onset Krabbe disease. Bone Marrow Transplant. 2008;41(9): 831–2.Google Scholar
33. Schiffmann, R, van der Knaap, MS. Invited article: an MRI-based approach to the diagnosis of white matter disorders. Neurology. 2009;72(8):750–9.CrossRefGoogle Scholar
34. Duffner, PK, Granger, C, Lyon, N, et al. Developmental and functional outcomes in children with a positive newborn screen for Krabbe disease: A pilot study of a phone-based interview surveillance technique. J Pediatr. 2012;161(2):258–63.e1.Google Scholar
35. Puckett, RL, Orsini, JJ, Pastores, GM, et al. Krabbe disease: clinical, biochemical and molecular information on six new patients and successful retrospective diagnosis using stored newborn screening cards. Mol Genet Metab. 2012;105(1):126–31.Google Scholar
36. Wenger, DA, Rafi, MA, Luzi, P, Datto, J, Costantino-Ceccarini, E. Krabbe disease: genetic aspects and progress toward therapy. Mol Genet Metab. 2000;70(1):1–9.Google Scholar
37. Tappino, B, Biancheri, R, Mort, M, et al. Identification and characterization of 15 novel GALC gene mutations causing Krabbe disease. Hum Mutat. 2010;31(12):E1894–914.Google Scholar
38. Lissens, W, Arena, A, Seneca, S, et al. A single mutation in the GALC gene is responsible for the majority of late onset Krabbe disease patients in the Catania (Sicily, Italy) region. Hum Mutat. 2007; 28(7):742.Google Scholar
39. Husain, AM, Altuwaijri, M, Aldosari, M. Krabbe disease: Neurophysiologic studies and MRI correlations. Neurology. 2004;63(4):617–20.Google Scholar
40. Aldosari, M, Altuwaijri, M, Husain, AM. Brain-stem auditory and visual evoked potentials in children with Krabbe disease. Clin Neurophysiol. 2004;115(7):1653–6.Google Scholar
41. Wang, C, Melberg, A, Weis, J, Mansson, JE, Raininko, R. The earliest MR imaging and proton MR spectroscopy abnormalities in adult-onset Krabbe disease. Acta Neurol Scand. 2007;116(4): 268–72.Google Scholar
42. De Stefano, N, Dotti, MT, Mortilla, M, et al. Evidence of diffuse brain pathology and unspecific genetic characterization in a patient with an atypical form of adult-onset Krabbe disease. J Neurol. 2000;247(3):226–8.Google Scholar
43. Brockmann, K, Dechent, P, Wilken, B, Rusch, O, Frahm, J, Hanefeld, F. Proton MRS profile of cerebral metabolic abnormalities in Krabbe disease. Neurology. 2003;60(5):819–25.Google Scholar
44. Loes, DJ, Peters, C, Krivit, W. Globoid cell leukodystrophy: distinguishing early-onset from late-onset disease using a brain MR imaging scoring method. AJNR Am J Neuroradiol. 1999; 20(2):316–23.Google Scholar
45. Duffner, PK, Barczykowski, A, Jalal, K, Yan, L, Kay, DM, Carter, RL. Early infantile Krabbe disease: results of the world-wide Krabbe registry. Pediatr Neurol. 2011;45(3):141–8.Google Scholar
46. Tullu, MS, Muranjan, MN, Kondurkar, PP, Bharucha, BA. Krabbe disease–clinical profile. Indian Pediatr. 2000;37(9):939–46.Google ScholarPubMed
47. Korn-Lubetzki, I, Dor-Wollman, T, Soffer, D, Raas-Rothschild, A, Hurvitz, H, Nevo, Y. Early peripheral nervous system manifestations of infantile Krabbe disease. Pediatr Neurol. 2003; 28(2):115–18.Google Scholar
48. Morse, LE, Rosman, NP. Myoclonic seizures in Krabbe disease: a unique presentation in late-onset type. Pediatr Neurol. 2006;35 (2):154–7.Google Scholar
49. Duffner, PK, Caviness, VS Jr, Erbe, RW, et al. The long-term outcomes of pre-symptomatic infants transplanted for Krabbe disease: report of the workshop held on July 11 and 12, 2008, Holiday Valley, New York. Genet Med. 2009;11(6):450–4.Google Scholar
50. Breningstall, GN, Patterson, RJ. Acquired obstructive hydrocephalus in globoid-cell leukodystrophy. Pediatr Neurol. 2008;39(4): 279–80.Google Scholar
51. Cavanagh, N, Kendall, B. High density on computed tomography in infantile Krabbe’s disease: a case report. Dev Med Child Neurol. 1986;28(6):799–802.Google Scholar
52. Morana, G, Biancheri, R, Dirocco, M, et al. Enhancing cranial nerves and cauda equina: an emerging magnetic resonance imaging pattern in Metachromatic Leukodystrophy and Krabbe disease. Neuropediatrics. 2009;40(6):291–4.Google Scholar
53. Hussain, SA, Zimmerman, HH, Abdul-Rahman, OA, Hussaini, SM, Parker, CC, Khan, M. Optic nerve enlargement in Krabbe disease: a pathophysiologic and clinical perspective. J Child Neurol. 2011;26(5):642–4.CrossRefGoogle ScholarPubMed
54. Kamate, M, Hattiholi, V. Normal neuroimaging in early-onset Krabbe disease. Pediatr Neurol. 2011;44(5):374–6.CrossRefGoogle ScholarPubMed
55. Provenzale, JM, Peddi, S, Kurtzberg, J, Poe, MD, Mukundan, S, Escolar, M. Correlation of neurodevelopmental features and MRI findings in infantile Krabbe’s disease. AJR Am J Roentgenol. 2009;192(1):59–65.Google Scholar
56. Barkovich, AJ, Raybaud, C. Pediatric neuroimaging. Philadelphia, US: Lippincott Williams and Wilkins; 2011.Google Scholar
57. Orsini, JJ, Morrissey, MA, Slavin, LN, et al. Implementation of newborn screening for Krabbe disease: population study and cutoff determination. Clin Biochem. 2009 Jun;42(9):877–84.Google Scholar
58. Li, Y, Scott, CR, Chamoles, NA, et al. Direct multiplex assay of lysosomal enzymes in dried blood spots for newborn screening. Clin Chem. 2004;50(10):1785–96.Google Scholar
59. Wenger, DA. Krabbe disease. In: Pagon, RA, Bird, TC, Dolan, CR, Stephens, K, editors. GeneReviews. Seattle (WA): University of Washington, Seattle; 1993.Google Scholar
60. Furuya, H, Kukita, Y, Nagano, S, et al. Adult onset Globoid Cell Leukodystrophy (Krabbe disease): analysis of galactosylceramidase cDNA from four Japanese patients. Hum Genet. 1997;100(3–4):450–6.Google Scholar
61. Tokimasa, S, Ohta, H, Takizawa, S, et al. Umbilical cord-blood transplantations from unrelated donors in patients with inherited metabolic diseases: single-institute experience. Pediatr Transplant. 2008;12(6):672–6.Google Scholar
62. Krivit, W, Shapiro, EG, Peters, C, et al. Hematopoietic stem-cell transplantation in globoid-cell leukodystrophy. N Engl J Med. 1998;338(16):1119–26.Google Scholar
63. Lee, WC, Kang, D, Causevic, E, Herdt, AR, Eckman, EA, Eckman, CB. Molecular characterization of mutations that cause globoid cell leukodystrophy and pharmacological rescue using small molecule chemical chaperones. J Neurosci. 2010;30(16): 5489–97.Google Scholar
64. Rafi, MA, Rao, HZ, Luzi, P, Curtis, MT, Wenger, DA. Extended normal life after AAVrh10-mediated gene therapy in the mouse model of Krabbe disease. Mol Ther. 2012;20(11):2031–42.Google Scholar
65. Neri, M, Ricca, A, di Girolamo, I, et al. Neural stem cell gene therapy ameliorates pathology and function in a mouse model of globoid cell leukodystrophy. Stem Cells. 2011;29(10):1559–71.Google Scholar