A 15-year-old girl with juvenile-onset metachromatic leukodystrophy (MLD) had markedly decreased leukocyte arylsulfatase A activity and low levels of leukocyte beta galactosidase and serum acid phosphatase.
The tear enzymes were assayed in most of the cases and demonstrated a profound deficiency of arylsulfatase A, or of arylsulfatase A and B, in the classical MLD and in mucosulfatidosis, respectively.
In an effort to improve the precision in prenatal monitoring for metachromatic leukodystrophy, levels of cerebroside sulfatase were determined in fibroblasts and amniotic fluid cells.
A comparison of genotypes, ARSA activities, and clinical data on 4 individuals carrying the allele of 81 patients with MLD examined, further validates the concept that different degrees of residual ARSA activity are the basis of phenotypical variation in MLD.
Cells from the clinically affected patients with MLD are completely deficient in arylsulfatase A activity, whereas those from the pseudodeficient individuals demonstrate a characteristic residual arylsulfatase A activity detectable only after electrophoresis.
Thus, reduction of ASA activity below 40% of the mean value of controls seems to be the critical threshold for elevated sulfatide excretion in MLD heterozygotes.
Two alleles (termed I and A) were identified and accounted for about half of all arylsulfatase A alleles among 68 patients with metachromatic leukodystrophy whom we examined.
An assay for the rapid detection of the arylsulfatase A pseudodeficiency allele facilitates diagnosis and genetic counseling for metachromatic leukodystrophy.
In a transient expression study, COS cells transfected with the mutant cDNA carrying 99Gly----Asp did not show an increase of ASA activity, which confirms that the mutation is a cause of adult-type MLD.
While most patients with metachromatic leukodystrophy have mutations in the gene for arylsulfatase A, some patients have deficient SAP-1, as determined by immunological techniques.
Cellulose acetate gel electrophoresis of fibroblast extracts from the patient showed no detectable arylsulfatase A isozyme under conditions that clearly distinguished pseudo-arylsulfatase A deficiency from classical MLD.
Complementation for ASA activity was found in hybrids between MSDv and metachromatic leukodystrophy (MLD) as well as between multiple sulphatase deficiency (MSD) and MLD.
The diagnosis of metachromatic leukodystrophy (MLD) was confirmed by the finding of low arylsulfatase A (ASA) levels in cultured fibroblasts in both sisters.