Krabbe Disease Treatment & Management

  • Author: David H Tegay, DO, FACMG; Chief Editor: Bruce Buehler, MD   more...
 
Updated: Jun 29, 2010
 

Medical Care

Following the emergence of hematopoietic stem cell transplantation (HSCT) as a potential treatment for Krabbe disease, newborn screening has been implemented in New York State with additional states scheduled to follow suit. Numerous studies in human and animal models have shown varying degrees of benefit with HSCT, with greatest benefit occurring in patients who are asymptomatic or mildly symptomatic and when transplanted within the 1st month of life.[34, 36]

HCST should be considered in individuals with late-onset or slowly progressive Krabbe disease and in individuals with infantile-onset disease, in the early neonatal asymptomatic period. Short-term benefits with HSCT are reported in the medical literature, including a suggestion of delayed progression and improved survival; however, transplantation mortality rates are 15%.

Data on long-term posttransplant neurocognitive and survival outcomes are accumulating. Positive long-term effects of HSCT in presymptomatic infants includes an apparent increase in length of survival, improvements in quality of life versus those that are not transplanted, and an attenuated degree of neurologic complications, with some retaining normal receptive language skills and developing ambulation (although usually requiring assistive devices).

Limitations of HSCT include the persistent development of neurologic deficits, most of which are progressive in nature, including microcephaly, spasticity, growth restriction, and developmental delay (both verbal and motor) with regression. Ultimately, lack of curative effect is associated with HSCT.[36]

Symptomatic treatment for some neurologic sequelae is available but has no significant effect on the clinical course.

Research continues into treatments targeting inflammatory markers,[37] enzyme replacement therapy, gene therapy, and neural stem cell transplantation, although this has not yet advanced to the point of clinical trials.

Next

Consultations

The following consultations are indicated:

  • Clinical geneticist - For initial evaluation and diagnosis, for counseling families regarding recurrence risk, and to help provide prenatal testing if desired in future pregnancies
  • Neurologist - For symptomatic therapy of the multiple neurologic sequelae
  • Ophthalmologist
  • Audiologist
Previous
Next

Diet

No known dietary modifications significantly alter the clinical course of Krabbe disease. Infants may ultimately require tube feedings for adequate energy intake; however, nutritional support does not change the disease course; therefore, some families may choose to forgo invasive alimentation methods.

Previous
Next

Activity

Neurologic sequelae may preclude adequate physical activity. Patients may benefit from physical and occupational therapy.

Previous
Proceed to Medication
 
 
Contributor Information and Disclosures
Author

David H Tegay, DO, FACMG  Associate Professor of Medicine and Medical Genetics, New York College of Osteopathic Medicine at the New York Institute of Technology; Assistant Professor of Pediatrics, Stony Brook University Medical Center

David H Tegay, DO, FACMG is a member of the following medical societies: American College of Medical Genetics, American College of Osteopathic Internists, American College of Physicians, American Medical Association, American Osteopathic Association, American Society of Human Genetics, and Federation of American Societies for Experimental Biology

Disclosure: Nothing to disclose.

Coauthor(s)

Rahmat A Balogun  New York College of Osteopathic Medicine at New York Institute of Technology

Rahmat A Balogun is a member of the following medical societies: American Osteopathic Association, Society for Neuroscience, and Student National Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Erawati V Bawle, MD, FAAP, FACMG  Retired Professor, Department of Pediatrics, Wayne State University School of Medicine

Erawati V Bawle, MD, FAAP, FACMG is a member of the following medical societies: American College of Medical Genetics and American Society of Human Genetics

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

David Flannery, MD, FAAP, FACMG  Vice Chair of Education, Chief, Section of Medical Genetics, Professor, Department of Pediatrics, Medical College of Georgia

David Flannery, MD, FAAP, FACMG is a member of the following medical societies: American Academy of Pediatrics and American College of Medical Genetics

Disclosure: Nothing to disclose.

Paul D Petry, DO, FACOP, FAAP  Consulting Staff, Freeman Pediatric Care, Freeman Health System

Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association

Disclosure: Nothing to disclose.

Chief Editor

Bruce Buehler, MD  Professor, Department of Pediatrics and Genetics, Director RSA, University of Nebraska Medical Center

Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association

Disclosure: Nothing to disclose.

References

  1. Suzuki K, Suzuki Y. Globoid cell leucodystrophy (Krabbe's disease): deficiency of galactocerebroside beta-galactosidase. Proc Natl Acad Sci U S A. Jun 1970;66(2):302-9. [Medline].

  2. Cleland WW, Kennedy EP. The enzymatic synthesis of psychosine. J Biol Chem. Jan 1960;235:45-51. [Medline]. [Full Text].

  3. Krabbe K. A new familial, infantile form of diffuse brain sclerosis. Brain. 1916;39:74.

  4. Suzuki K. Globoid cell leukodystrophy (Krabbe's disease): update. J Child Neurol. Sep 2003;18(9):595-603. [Medline].

  5. Wenger DA, Suzuki K, Suzuki Y, Suzuki K. 147. In: Galactosylceramide lipidosis: globoid cell leukodystrophy (Krabbe disease). In: Scriver CR, Beaudet AL, Sly WS, Valle D, Vogelstein B (eds) The Metabolic and Molecular Bases of Inherited Disease (OMMBID). McGraw-Hill; New York, NY: McGraw-Hill:2005.

  6. Caniglia M, Rana I, Pinto RM, et al. Allogeneic bone marrow transplantation for infantile globoid-cell leukodystrophy (Krabbe's disease). Pediatr Transplant. Oct 2002;6(5):427-31. [Medline].

  7. Escolar ML, Poe MD, Provenzale JM, et al. Transplantation of umbilical-cord blood in babies with infantile Krabbe's disease. N Engl J Med. May 19 2005;352(20):2069-81. [Medline].

  8. Krivit W, Shapiro EG, Peters C, et al. Hematopoietic stem-cell transplantation in globoid-cell leukodystrophy. N Engl J Med. Apr 16 1998;338(16):1119-26. [Medline]. [Full Text].

  9. Martin PL, Carter SL, Kernan NA, et al. Results of the cord blood transplantation study (COBLT): outcomes of unrelated donor umbilical cord blood transplantation in pediatric patients with lysosomal and peroxisomal storage diseases. Biol Blood Marrow Transplant. Feb 2006;12(2):184-94. [Medline].

  10. Meikle PJ, Ranieri E, Simonsen H, et al. Newborn screening for lysosomal storage disorders: clinical evaluation of a two-tier strategy. Pediatrics. Oct 2004;114(4):909-16. [Medline]. [Full Text].

  11. Igisu H, Suzuki K. Progressive accumulation of toxic metabolite in a genetic leukodystrophy. Science. May 18 1984;224(4650):753-5. [Medline].

  12. Miyatake T, Suzuki K. Globoid cell leukodystrophy: additional deficiency of psychosine galactosidase. Biochem Biophys Res Commun. Aug 7 1972;48(3):539-43. [Medline].

  13. White AB, Givogri MI, Lopez-Rosas A, Cao H, van Breemen R, Thinakaran G. Psychosine accumulates in membrane microdomains in the brain of krabbe patients, disrupting the raft architecture. J Neurosci. May 13 2009;29(19):6068-77. [Medline].

  14. Mohri I, Taniike M, Taniguchi H, Kanekiyo T, Aritake K, Inui T. Prostaglandin D2-mediated microglia/astrocyte interaction enhances astrogliosis and demyelination in twitcher. J Neurosci. Apr 19 2006;26(16):4383-93. [Medline].

  15. Giri S, Khan M, Nath N, Singh I, Singh AK. The role of AMPK in psychosine mediated effects on oligodendrocytes and astrocytes: implication for Krabbe disease. J Neurochem. Jun 2008;105(5):1820-33. [Medline].

  16. Zlotogora J, Regev R, Zeigler M, et al. Krabbe disease: increased incidence in a highly inbred community. Am J Med Genet. Aug 1985;21(4):765-70. [Medline].

  17. Wenger DA, Rafi MA, Luzi P. Molecular genetics of Krabbe disease (globoid cell leukodystrophy): diagnostic and clinical implications. Hum Mutat. 1997;10(4):268-79. [Medline].

  18. 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. Aug 1985;16(3):137-42. [Medline].

  19. Lyon G, Hagberg B, Evrard P, et al. Symptomatology of late onset Krabbe's leukodystrophy: the European experience. Dev Neurosci. 1991;13(4-5):240-4. [Medline].

  20. Hagberg B. The clinical diagnosis of Krabbe's infantile leucodystrophy. Acta Paediatr Scand. 1963;52:213.

  21. Dunn HG, Lake BD, Dolman CL, Wilson J. The neuropathy of Krabbe's infantile cerebral sclerosis (globoid cell leucodystrophy). Brain. 1969;92(2):329-44. [Medline].

  22. Korn-Lubetzki I, Dor-Wollman T, Soffer D, et al. Early peripheral nervous system manifestations of infantile Krabbe disease. Pediatr Neurol. Feb 2003;28(2):115-8. [Medline].

  23. Sedel F, Tourbah A, Fontaine B, Lubetzki C, Baumann N, Saudubray JM. Leukoencephalopathies associated with inborn errors of metabolism in adults. J Inherit Metab Dis. Jun 2008;31(3):295-307. [Medline].

  24. Nyhan WL, Ozand PT. Krabbe disease/galactosylceramide lipidosis/globoid cell leukodystrophy. In: Atlas of Metabolic Disease. New York, NY: Chapman & Hall Medical; 1998:581-5.

  25. Luzi P, Rafi MA, Wenger DA. Structure and organization of the human galactocerebrosidase (GALC) gene. Genomics. Mar 20 1995;26(2):407-9. [Medline].

  26. Oehlmann R, Zlotogora J, Wenger DA, Knowlton RG. Localization of the Krabbe disease gene (GALC) on chromosome 14 by multipoint linkage analysis. Am J Hum Genet. Dec 1993;53(6):1250-5. [Medline].

  27. Farrell DF, Percy AK, Kaback MM, McKhann GM. Globoid cell (Krabbe's) leukodystrophy: heterozygote detection in cultured skin fibroblasts. Am J Hum Genet. Nov 1973;25(6):604-9. [Medline].

  28. Wenger DA, Sattler M, Clark C, McKelvey H. An improved method for the identification of patients and carriers of Krabbe's disease. Clin Chim Acta. Oct 30 1974;56(2):199-206. [Medline].

  29. Bowen DM, Radin NS. Cerebroside galactosidase: a method for determination and a comparison with other lysosomal enzymes in developing rat brain. J Neurochem. Apr 1969;16(4):501-11. [Medline].

  30. Duffner PK, Caggana M, Orsini JJ, et al. Newborn screening for Krabbe disease: the New York State model. Pediatr Neurol. Apr 2009;40(4):245-52; discussion 253-5. [Medline].

  31. Lane B, Carroll BA, Pedley TA. Computerized cranial tomography in cerebral diseases of white matter. Neurology. Jun 1978;28(6):534-44. [Medline].

  32. Brockmann K, Dechent P, Wilken B, et al. Proton MRS profile of cerebral metabolic abnormalities in Krabbe disease. Neurology. Mar 11 2003;60(5):819-25. [Medline].

  33. 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. Jan 2009;192(1):59-65. [Medline].

  34. Provenzale JM, Escolar M, Kurtzberg J. Quantitative analysis of diffusion tensor imaging data in serial assessment of krabbe disease. Ann N Y Acad Sci. Dec 2005;1064:220-9. [Medline].

  35. Austin JH, Lehfeldt D. Studies in globoid (Krabbe) leucodystrophy. 3. Significance of experimentally produced globoid-like elements in rat white matter and spleen. J Neuropathol Exp Neurol. Apr 1965;24:265-89. [Medline].

  36. Duffner PK, Caviness VS Jr, Erbe RW, Patterson MC, Schultz KR, Wenger DA. 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. Jun 2009;11(6):450-4. [Medline].

  37. Luzi P, Abraham RM, Rafi MA, Curtis M, Hooper DC, Wenger DA. Effects of treatments on inflammatory and apoptotic markers in the CNS of mice with globoid cell leukodystrophy. Brain Res. Dec 1 2009;1300:146-58. [Medline].

  38. 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. Sep 2008;12(6):672-6. [Medline].

 
Previous
Next
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.