Late juvenile metachromatic leukodystrophy (MLD) in three patients with a similar clinical course and identical mutation on one allele

Clin Genet. 1996 Nov;50(5):287-92. doi: 10.1111/j.1399-0004.1996.tb02376.x.


Metachromatic leukodystrophy (MLD) is an autosomal, recessively inherited, lysosomal storage disease caused by arylsulfatase A (ASA) activity deficit. Arylsulfatase A initiates the degradation of sulfatide (cerebroside sulfate), which is an essential component of myelin. The main clinical symptoms are caused by progressive demyelination. At least 34 MLD-related ASA mutations are known to date. I179S (E3P799) is a disease-related mutation, described for the first time by Fluharty in 1991. This aberration appears to substantially reduce, but not completely eliminate ASA activity, and was detected in individuals with late-onset (juvenile or adult) forms of MLD. This paper deals with the peculiar clinical course in three unrelated juveniles with late-onset MLD carrying the I179S mutations on one allele. In the three described patients with the I179S mutation, psychiatric disturbances and intellectual impairment dominated the clinical picture, while the neurological lesions 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 mutations on the second allele in our patients are unknown, one can speculate, that the mutation I179S plays an important role in the characteristic clinical course (psychiatric impairment, slower neurological deterioration, but relatively early onset). It seems that I179S mutation on one allele with another mutation on the other allele reduces ASA activity, but the enzyme can still cope with a part of the substrate influx, leading to late-juvenile-onset MLD with such strikingly similar phenotypes remaining a little bit of the adult (psychiatric) type. This could be one more argument in favour of phenotype-genotype correlation in patients with MLD.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alleles*
  • Cerebroside-Sulfatase / genetics*
  • Cerebroside-Sulfatase / metabolism
  • Female
  • Humans
  • Leukodystrophy, Metachromatic / enzymology*
  • Leukodystrophy, Metachromatic / genetics
  • Leukodystrophy, Metachromatic / physiopathology
  • Male
  • Mutagenesis
  • Pedigree
  • beta-Galactosidase / metabolism


  • Cerebroside-Sulfatase
  • beta-Galactosidase