LATE JUVENILE METACHROMATIC LEUKODYSTROPHY (MLD) IN 3 PATIENTS WITH ASIMILAR CLINICAL COURSE AND IDENTICAL MUTATION ON ONE ALLELE

Metachromatic leukodystrophy (MLD) is an autosomal, recessively inheri ted, lysosomal storage disease caused by arylsulfatase A (ASA) activit y deficit. Arylsulfatase A initiates the degradation of sulfatide (cer ebroside sulfate), which is an essential component of myelin. The main clinical symptoms are caused by progressive demyelination. At least 3 7 MLD-related ASA mutations are known to date. I179S (E3P799) is a dis ease-related mutation, described for the first time by Fluharty in 199 1. This aberration appears to substantially reduce, but not completely eliminate ASA activity, and was detected in individuals with late-ons et (juvenile or adult) forms of MLD. This paper deals with the peculia r clinical course in three unrelated juveniles with late-onset MLD car rying the I179S mutation on one allele. In the three described patient s with the I179S mutation, psychiatric disturbances and intellectual i mpairment dominated the clinical picture, while the neurological lesio ns progressed more slowly. Although the symptoms appeared rather early , making it possible to classify this as the juvenile type of MLD, the clinical picture was more that of the adult type. Although the mutati ons on the second allele in our patients are unknown, one can speculat e, that the mutation I179S plays an important role in the characterist ic clinical course (psychiatric impairment, slower neurological deteri oration, but relatively early onset). It seems that I179S mutation on one allele with another mutation on the other allele reduces ASA activ ity, but the enzyme can still cope with a part of the substrate influx , leading to late-juvenile-onset MLD with such strikingly similar phen otypes remaining a little bit of the adult (psychiatric) type. This co uld be one more argument in favour of phenotype-genotype correlation i n patients with MLD.