title: Neuroradiological, neurophysiological and molecular findings in infantile Krabbe disease: two case reports.
abstract: Krabbe disease is an autosomal recessive neurodegenerative disorder due to a defect of the lysosomal enzyme β-galactocerebrosidase (β-GALC). Depending on the age of onset, the disease is classified into infantile and later-onset forms. We report neuroradiological, neurophysiological and molecular findings in two Greek patients with the infantile form of Krabbe disease. The index patients presented at the age of 3.5 and 6 months, respectively, due to developmental delay. Magnetic resonance imaging (MRI) of the first patient's brain demonstrated signs of leukodystrophy, while nerve conduction velocities (NCVs) were significantly decreased. The second patient's MRI at the age of 4 months was initially normal, but at 18 months demonstrated leukodystrophic alterations as well, whereas NCVs were also significantly delayed. In both patients, a severe decrease in β-GALC, activity supported the diagnosis of Krabbe disease, while the final diagnosis was confirmed by molecular genetic testing. Two homozygous mutations of theGALCgene, the c.411_413delTAA [p.K139del] mutation in the first patient, and the c.749T>C [p.I250T] mutation in the second patient, were identified. At their last follow-up visit at the age of 4 and 6 years, respectively, both patients were bedridden and quadri-plegic, suffering from frequent respiratory tract infections and fed through a gastrostomy. Both mutations found in homozygosity in these two unrelated patients of Greek ancestry, could pinpoint a common origin. Genotyping of patients with Krabbe disease is important, in order to contribute to the creation of a European mutation database and to further study possible genotype-phenotype correlations of the disease.
authors: 1 Pediatric Clinic, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors: E
authors: E
authors: Vargiami
authors: 1 Pediatric Clinic, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors: E
authors: E
authors: Papathanasiou
authors: 1 Pediatric Clinic, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors: S
authors: S
authors: Batzios
authors: 1 Pediatric Clinic, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors: M
authors: M
authors: Kyriazi
authors: Department of Enzymology and Cellular Function, Institute of Child Health, Athens, Greece.
authors: E
authors: E
authors: Dimitriou
authors: Department of Radiology, Hippokratio General Hospital, Thessaloniki, Greece.
authors: A
authors: A
authors: Anastasiou
authors: Department of Enzymology and Cellular Function, Institute of Child Health, Athens, Greece.
authors: H
authors: H
authors: Michelakakis
authors: Neurogenetics and Metabolic Disorders Unit, University of Rostock, Rostock, Germany.
authors: A-K
authors: AK
authors: Giese
authors: 1 Pediatric Clinic, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors: D I
authors: DI
authors: Zafeiriou
keywords: GALC gene; Krabbe disease; Leukodystrophy; Mutation; Nerve conduction velocity (NCV); β-galactocerebrosidase (β-GALC)