title: The Spectrum of Krabbe Disease in Greece: Biochemical and Molecular Findings.
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.
authors.affiliation: Department Enzymology and Cellular Function, Institute of Child Health, Athens, Greece.
authors.forename: Evangelia
authors.initials: E
authors.lastname: Dimitriou
authors.affiliation: Department of Genetics, Faculty of Biology, Universitat de Barcelona, IBUB, CIBERER, Barcelona, Spain.
authors.forename: Monica
authors.initials: M
authors.lastname: Cozar
authors.affiliation: Department Enzymology and Cellular Function, Institute of Child Health, Athens, Greece.
authors.forename: Irene
authors.initials: I
authors.lastname: Mavridou
authors.affiliation: Department of Genetics, Faculty of Biology, Universitat de Barcelona, IBUB, CIBERER, Barcelona, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Grinberg
authors.affiliation: Department of Genetics, Faculty of Biology, Universitat de Barcelona, IBUB, CIBERER, Barcelona, Spain.
authors.forename: Lluïsa
authors.initials: L
authors.lastname: Vilageliu
authors.affiliation: Department Enzymology and Cellular Function, Institute of Child Health, Athens, Greece. ecfdept@ich.gr.
authors.forename: Helen
authors.initials: H
authors.lastname: Michelakakis