engleski

Lower arylsulfatase A activity in cerebral palsy - A possible contribution of mutations associated with arylsulfatase A pseudodeficiency and metachromatic leukodystrophy

Arylsulfatase A (ASA, EC 3.1.6.1) is a lysosomal enzyme involved in sulfatide catabolism. In the central nervous system, sulfatides represent a major lipid constituent of oligodendrocyte membranes, and contribute to maintenance of myelin sheath integrity. Deficiency of ASA causes metachromatic leukodystrophy (MLD), rare autosomal recessive disorder characterized by the storage of cerebroside sulfate mainly in the nervous tissue. The onset and clinical severity of the disease are related to the type of mutation in ASA gene and consequently to the level of enzyme deficiency. Two most frequent MLD mutations are 459+1G>A and P426L mutation. Low ASA activities have been also reported in healthy individuals and several neurological and psychiatric disorders, due to condition termed ASA pseudodeficiency (ASA-PD). Two mutations in the ASA gene, responsible for the majority of pseudodeficiency alleles, are designated as N350S and 1524+95 A>G mutation. Our previous analysis of ASA-PD associated mutations showed significantly higher frequency of mutated alleles in patients with diagnosis of spastic form of cerebral palsy in comparison with healthy individuals. Also, lower activity of arylsulfatase A was found in majority of patients, as determined by spectrophotometry using p-nitrocatechol sulfate as chromogenic substrate. The aim of this preliminary study was to establish the frequency of two most frequent MLD mutations in the same group of patients with cerebral palsy. For this purpose, genomic DNA was extracted from leukocytes and fragments of ASA gene were amplified using specific primers. After digestion with adequate restriction enzymes, the reaction products were analyzed by electrophoresis on 2-3 % agarose gel. Finally, the frequency of analyzed MLD mutations was estimated in patients and compared with healthy subjects. In conclusion, our results show decreased activities of ASA in majority of patients with spastic cerebral palsy. The presence of ASA-PD and MLD mutations, as well as other yet undescribed mutations in ASA gene, may contribute to observed lower ASA activities in cerebral palsy.

arylsulfatase A; cerebral palsy; mutations associated with arylsulfatase A pseudodeficiency and metachromatic leukodystrophy

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