Olkhovich N. Analysis of the ASA gene mutations and the peculiarities of the biochemical diagnostics of the metachromatic leukodystrophy

The inherited disease - metachromatic leykodystrophy. The dissertation is devoted to studing for the frequencies and spectrum of MLD caused mutations and the biochemical basis of the metachromatic leukodystrophy (MLD) in Ukrainian MLD patients. The mutation database of the ARSA gene is created. The frequencies and spectrum of MLD caused mutations in Ukrainian MLD patients are detected. The frequency of major mutations in the ASA gene in Ukrainian MLD patients is 20%. The genotype-phenotype correlation is studied and the results of investigation are compared with known information about genetic characteristics of MLD in different populations. The frequency of ASA pseudodeficiency allele in health individuals in Ukraine is 7,7%. Biochemical diagnostic of MLD is complicated by arylsulfatase A pseudodeficiency. There is possibility of mistake in MLD diagnostic in case of pseudodeficiency ARSA and non-MLD neurological disease combination. We suggest the new modification of arylsulfatase A activity detection method which allow to identify the arylsulfatase A pseudodeficiency without molecular genetic methods. We suggest the high informative algorithm for the MLD diagnostics and carriers screening in Ukraine. Sphere of use is the medical genetic, the inherited diseases diagnostic.