Aryl sulfatase A deficiency in psychiatric and neurologic patients

Abstract

Two hundred ninety-five psychiatric and neurologic patients were randomly screened for aryl sulfatase A (ASA) activity in lymphocyte extracts. Two of these patients showed very low ASA activity, in the range of metachromatic leukodystrophy (MLD)-affected patients. The residual activity in these low ASA patients showed normal enzyme behavior with regard to ASA kinetic features and the ability to catabolize 14C labeled sulfatide by intact fibroblasts. Taking into account that approximately 3% of the general population are homozygous for the pseudo-aryl sulfatase A gene and are clinically unaffected, the data obtained here indicate that the patients studied in this work, as well as most psychiatric patients reported in the literature with low ASA activity, represent the normal ASA polymorphism. Thus, the very low ASA activity patients are in fact homozygous for the pseudo-deficient allele, which does not result in clinical abnormalities. The clinical symptoms in these psychiatric patients and probably other "variant" MLD patients are therefore not related to low ASA activity.

The relationship of the metachromatic leukodystrophies to neuropsychiatric disorders

“…If the prevalence of the pseudodeficient allele is between 10 and 15%, as has been suggested recently, these numbers are not higher than would be expected in the general population. Herska et al (1987) obtained similar results with a group of about 300 psychiatric and neurological disease patients in Israel. There were two individuals with very low ARS-A activity.…”

Arylsulfatase A (ASA) defect and psychiatric illness

“…There are a number of differences in the two assay systems, e.g., the sonication vs. the freeze thaw method used for solubilization. Although the mean values for ASA activity reported by Bach's group (Herz and Bach, 1984;Herska et al, 1987), Propping's group (1987) and that of Hoes et al (1988) are in close agreement, the values are one-half to one-third of those observed by us (Shah et al, 1985), and one-tenth of the values reported by Manowitz et al (1981). It should be noted that Bach's group assayed ASA activity in lymphocytes, rather than leukocyte preparations used by the other four groups.…”

“…The average value for ASA-CS in psychiatric patients did not differ significantly from the average for normals. Three other studies investigating ASA-NCS activity in psychiatric patients have since been reported (Propping et al, 1986;Herska et al, 1987;Hoes et al 1988). The results of all five studies on leukocyte ASA-NCS activities are summarized in Table 1.…”

Genotype-phenotype relationship in various degrees of arylsulfatase A deficiency

“…The same is apparently true for the cells of the nervous system, since (a) ASAp/ASAp is no more frequent in large samples of neuropsychiatric patients than in healthy controls (Herska et al 1987;Hohenschutz et al 1989) and (b) the diagnoses in this group have no resemblance to established MLD phenotypes but rather reflect the structure of the patient sample examined. Thus, clinical symptomatology in the patients may be coincidental.…”

“…Probably, some of the observed variability must be ascribed to misdiagnoses in cases where a neurologic disease coincides with a causally unrelated pseudodeficiency (Farrell et al 1985;Herska et al 1987;Kappler et al 1990).…”