Abstract
A profound deficiency of arylsulfatase A activity (ARA) is detectable in skin fibroblasts developed from patients with infantile metachromatic leukodystrophy (about 3 to 4 per cent of normal). Fibroblasts were cultivated from skin biopsies of parents and siblings in four unrelated families in which a child with infantile metachromatic leukodystrophy had been documented. Fibroblast ARA activities of seven parents ranged from three to 15 times higher than those found in the affected patients, but were below the activity measured in control fibroblasts, confirming an autosomal recessive mode of inheritance for this disease.
ARA specific activity in cultured cells from normal mid-trimester amniotic-fluid samples is significantly lower than that found in control skin fibroblast cultures. Hence values found in amniotic-fluid cell cultures do not necessarily identify the fetus with metachromatic leukodystrophy.
WE have recently characterized the enzyme arylsulfatase A (ARA) in normal human skin fibroblasts cultivated in vitro, and established a profound deficiency of this enzyme in fibroblast cells cultured from patients with infantile metachromatic leukodystrophy (MLD).
1
Simultaneously, and independently, others have detected diminished ARA activity in skin fibroblasts cultured from a child with this disease.
2
A generalized deficiency of this enzyme had previously been documented in many tissues,
3
including brain
3
and leukocytes,
4
as well as in urine
5
from patients with MLD.
ARA catalyzes the hydrolytic desulfation of nitrocatechol sulfate, a synthetic substrate. This enzyme activity has been shown to be . . .