Prevalence of partial cerebroside sulfate sulfatase (Arylsulfatase A) defect in adult psychiatric patients

Metachromatic leukodystrophy (MLD) is a disease caused by a deficiency of the enzyme sulfatide sulfatase, also known as arylsulfatase A (ASA). We compared the activity of this enzyme in adult psychiatric patients and normal volunteers using nitrocatechol sulfate (ASA-NCS) and cerebroside sulfate (ASA-CS) as substrates. Our results showed that ASA-NCS activity in urine and leukocytes was significantly lower in psychiatric than in normal individuals, but that there were no differences between these two groups in the sulfatide excretion in urine or the ASA-CS activity in leukocytes. There was no correlation between enzyme activity in urine and in leukocytes, indicating that activity in urine does not truly reflect the levels of the enzyme in tissues. The correlation between ASA-NCS and ASA-CS activity in leukocytes was poor (0.51 for psychiatric patients and 0.59 for normals), suggesting that for a valid measure of the enzyme activity the assays should be carried out with CS as substrate. Results of our study also indicate that in 39 of the 145 psychiatric patients studied, the ASA-CS activity in leukocyte was less than 4 nmoles/mg protein/hr, which is below 50% of the normal means, whereas only one of the 30 normal subjects had a value this low. The presence of low levels of ASA-CS activity in a significantly large number of adult patients with varying psychiatric manifestations suggests that such patients may be asymptomatic carriers of the sulfatidase defect (heterozygotes for MLD), and that behavioral and functional disturbances in these patients may at least in part be related to sulfatidase deficiency. The significance of the ASA-NCS abnormality (reduction) in psychiatric patients is unclear.