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Globoid cell leukodystrophy (Krabbe disease): normal umbilical cord blood galactocerebrosidase activity and polymorphic mutations.

Publication ,  Journal Article
Raghavan, S; Zeng, B; Torres, PA; Pastores, GM; Kolodny, EH; Kurtzberg, J; Krivit, W
Published in: J Inherit Metab Dis
2005

Globoid cell leukodystrophy is an inherited metabolic disorder of the central nervous system caused by deficiency of the lysosomal enzyme galactocerebrosidase. Haematopoietic stem cell transplantation is the only available effective treatment. The engraftment from normal donors provides competent cells able to correct the metabolic defect. Umbilical cord blood cells have proved to significantly decrease complications and improve engraftment rate compared to adult marrow cells in haematopoietic stem cell transplantation. Umbilical cord blood cells must be of sufficient activity to provide central nervous system recovery after engraftment is obtained. Galactocerebrosidase activity is known to be affected by two polymorphic alleles found at nucleotides 502 and 1637 of the cDNA for this gene. This enzyme activity and the polymorphic alleles noted above were analysed in 83 random samples of umbilical cord blood. The activity, assayed with the fluorogenic substrate 6-hexadecanoylamino-4-methylumbelliferyl-beta-galactopyranoside, in those with neither polymorphic allele was 4.6 +/- 1.7 units (nmol/h per mg protein). This optimal choice of cord blood was found in only 24% of specimens. Homozygotes for 1637T > C with activity of only 1.5 +/- 0.4 units represented 16% of the samples. Those heterozygous for 1637T > C with slightly better activity (2.3 +/- 0.7 units) represented 52% of the samples. Choice of umbilical cord blood for haematopoietic stem cell transplantation, therefore, requires consideration not only of cell quantity and HLA compatibility but also selection for normal alleles to obtain maximal enzymatic activity for central nervous system correction.

Duke Scholars

Published In

J Inherit Metab Dis

DOI

ISSN

0141-8955

Publication Date

2005

Volume

28

Issue

6

Start / End Page

1005 / 1009

Location

United States

Related Subject Headings

  • Polymorphism, Genetic
  • Mutation
  • Lysosomes
  • Leukodystrophy, Globoid Cell
  • Hymecromone
  • Humans
  • Homozygote
  • Heterozygote
  • Hematopoietic Stem Cell Transplantation
  • HLA Antigens
 

Citation

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ICMJE
MLA
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Raghavan, S., Zeng, B., Torres, P. A., Pastores, G. M., Kolodny, E. H., Kurtzberg, J., & Krivit, W. (2005). Globoid cell leukodystrophy (Krabbe disease): normal umbilical cord blood galactocerebrosidase activity and polymorphic mutations. J Inherit Metab Dis, 28(6), 1005–1009. https://doi.org/10.1007/s10545-005-4138-z
Raghavan, S., B. Zeng, P. A. Torres, G. M. Pastores, E. H. Kolodny, J. Kurtzberg, and W. Krivit. “Globoid cell leukodystrophy (Krabbe disease): normal umbilical cord blood galactocerebrosidase activity and polymorphic mutations.J Inherit Metab Dis 28, no. 6 (2005): 1005–9. https://doi.org/10.1007/s10545-005-4138-z.
Raghavan S, Zeng B, Torres PA, Pastores GM, Kolodny EH, Kurtzberg J, et al. Globoid cell leukodystrophy (Krabbe disease): normal umbilical cord blood galactocerebrosidase activity and polymorphic mutations. J Inherit Metab Dis. 2005;28(6):1005–9.
Raghavan, S., et al. “Globoid cell leukodystrophy (Krabbe disease): normal umbilical cord blood galactocerebrosidase activity and polymorphic mutations.J Inherit Metab Dis, vol. 28, no. 6, 2005, pp. 1005–09. Pubmed, doi:10.1007/s10545-005-4138-z.
Raghavan S, Zeng B, Torres PA, Pastores GM, Kolodny EH, Kurtzberg J, Krivit W. Globoid cell leukodystrophy (Krabbe disease): normal umbilical cord blood galactocerebrosidase activity and polymorphic mutations. J Inherit Metab Dis. 2005;28(6):1005–1009.
Journal cover image

Published In

J Inherit Metab Dis

DOI

ISSN

0141-8955

Publication Date

2005

Volume

28

Issue

6

Start / End Page

1005 / 1009

Location

United States

Related Subject Headings

  • Polymorphism, Genetic
  • Mutation
  • Lysosomes
  • Leukodystrophy, Globoid Cell
  • Hymecromone
  • Humans
  • Homozygote
  • Heterozygote
  • Hematopoietic Stem Cell Transplantation
  • HLA Antigens