Neuroradiological, neurophysiological and molecular findings in infantile Krabbe disease: two case reports

Balkan Journal of Medical Genetics - Tập 19 Số 1 - Trang 85-90 - 2016
E. Vargiami1,2, E Papathanasiou1,3,4,5,2, Spyros Batzios1,2, Maria Kyriazi1,2, Evangelia Dimitriou3,4,5,2,6, Athanasia Anastasiou4, Helen Michelakakis3, Anne‐Katrin Giese5, Dimitrios I. Zafeiriou1,3,4,5,2
11 st Pediatric Clinic, Aristotle University of Thessaloniki, Thessaloniki, Greece
2st Department of Pediatrics, Aristotle University of Thessaloniki, Egnatia St. 106, 54622 Thes-saloniki, Greece.
3Department of Enzymology and Cellular Function, Institute of Child Health, Athens, Greece
4Department of Radiology, Hippokratio General Hospital, Thessaloniki, Greece
5Neurogenetics and Metabolic Disorders Unit, University of Rostock, Rostock, Germany
6st Pediatric Clinic, Aristotle University of Thessaloniki, Thessaloniki, Greece

Tóm tắt

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 the GALC gene, 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.

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Tài liệu tham khảo

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Thông tin xuất bản

Balkan Journal of Medical Genetics

Tập 19 Số 1

85-90

Thông tin tác giả