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The Spectrum of Krabbe Disease in Greece: Biochemical and Molecular Findings

  • Evangelia Dimitriou
  • Monica Cozar
  • Irene Mavridou
  • Daniel Grinberg
  • Lluïsa Vilageliu
  • Helen MichelakakisEmail author
Research Report
Part of the JIMD Reports book series (JIMD, volume 25)

Abstract

Krabbe disease is an autosomal recessive neurodegenerative lysosomal storage disease caused by the deficiency of β-galactocerebrosidase. This deficiency results in the impaired degradation of β-galactocerebroside, a major myelin lipid, and of galactosylsphingosine. Based on the age of onset of neurological symptoms, an infantile form (90% patients) and late-onset forms (10% patients) of the disease are recognized. Over 130 disease-causing mutations have been identified in the β-galactocerebrosidase gene. We present the biochemical and molecular findings in 19 cases of Krabbe disease, 17 of them unrelated, diagnosed in Greece over the last 30 years. β-Galactocerebrosidase activity assayed in leukocyte homogenates using either the tritium-labeled or the fluorescent substrate was diagnostic for all. Increased plasma chitotriosidase activity was found in 11/15 patients.

Mutational analysis, carried out in 11 unrelated cases, identified seven different mutations, four previously described (p.I250T, c.1161+6532_polyA+9kbdel, p.K139del, p.D187V) and three novel mutations (p.D610A, c.583-1 G>C, p.W132X), and seven distinct genotypes. The most prevalent mutation was mutation p.I250T, first described in a patient of Greek origin. It accounted for 36.4% (8/22) of the mutant alleles. The second most frequent mutation was c.1161+6532_polyA+9kbdel that accounted for 22.7% (5/22) of the mutant alleles. The observed frequency was lower than that described in Northern European countries and closer to that described in Italian patients.

Keywords

Lysosomal Storage Disorder Lysosomal Storage Disease Infantile Form Chitotriosidase Activity Plasma Chitotriosidase Activity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

We are grateful to Prof. Zafeiriou, Dr. Garoufi, Dr. Skiadas, Dr. Lourbopoulos, and all the clinicians that collaborated with us in the diagnosis of the Krabbe patients. We are also grateful to A. Bayona for technical help. This work was partially supported by grants SAF2011-25431 from the Spanish Ministry of Science and Innovation and 2009SGR971 and 2014SGR932, from the Catalan Government.

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Copyright information

© SSIEM and Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Evangelia Dimitriou
    • 1
  • Monica Cozar
    • 2
  • Irene Mavridou
    • 1
  • Daniel Grinberg
    • 2
  • Lluïsa Vilageliu
    • 2
  • Helen Michelakakis
    • 1
    Email author
  1. 1.Department Enzymology and Cellular FunctionInstitute of Child HealthAthensGreece
  2. 2.Department of Genetics, Faculty of BiologyUniversitat de Barcelona, IBUB, CIBERERBarcelonaSpain

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