Molecular diagnostics of the Krabbe disease in Russian children

Introduction. Krabbe disease (KD) is the lysosomal storage disease developed due to the decline of the galactocerebrosidase activity associated with mutations in the GALC gene. It leads to the development of oligodendrocytes and lemmocytes (Schwann cells) myelin-forming dysfunction. Nowadays the only possible treatment of KD is hemopoietic cell transplantation which should be performed before the manifestation of any signs of disease. That is why laboratory diagnostics has special significance.

The aim of the study. To elaborate the algorithm of a molecular diagnostics of the Krabbe disease (KD) in Russian children.

Material and methods. 190 patients were diagnosed for the exclusion of KD during the period from 2012 to 2019. In all cases, there was measured a galactocerebrosidase activity in dry blood spots. In cases with the declined enzyme activity, there was performed a further search of pathogenic variants in the GALC gene. The concentration of glycosyl sphingosine (Lyso-GL1) biomarker was measured in 90 patients included in the study since 2016.

Results. The enzyme activity was decreased in all patients in comparison with the control group (0.33±0.05; 2.95±0.24 µmol/l/h, (p<0.001; CI: 95%) in 9 patients. Also, we revealed an increased concentration of Lyso-GL1 biomarker in matched controls (12.50±1.57 ng/ml; 1.8±0.33 ng/ml, (p<0.005; CI: 95%) in 5 patients. During molecular genetic testing of KD, three novel pathogenic variants of the GALC gene were revealed in 3 out of 9 patients: c.265-2A>G, c.1036del and c.2037_2040del.

Conclusion. The Lyso-GL1 concentration measurement can be used as an additional diagnostics method of KD. The high efficiency of the presented algorithm for the KD diagnostics in Russian children is presented.

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