Metabolism of fatty acid-labeled cerebroside sulfate in cultured cells from controls and metachromatic leukodystrophy patients. Use in the prenatal identification of a false positive fetus.

Metachromatic leukodystrophy is the name given to a group of diseases in patients having a deficiency of CS sulfatase activity. The diagnosis usually can be made by using leukocytes, urine, and cultured skin fibroblasts. The low level of enzyme activity can be measured with an artificial substrate, NCS, or suitably labeled CS. In a number of families, healthy carriers of this autosomal recessive disease have been found to have enzyme levels near those of affected patients. We prepared (14)C-stearic acid-labeled CS and studied its metabolism in cultured human cells from patients and controls, In vitro, CS sulfatase requires bile salts to stimulate the enzymatic reaction. The (14)C-CS also can be added to the medium on cultured cells, and its metabolism in the cells can be followed without the addition of bile salts. A child with late infantile MLD was identified by studies on urine and leukocytes. Studies on leukocytes from the parents revealed a very low enzyme level in the father (false positive) and a typical carrier level in the mother. A pregnancy in this family was monitored, and in vitro studies on cultured AFC revealed low CS and NCS sulfatase levels. However, the addition of (14)C-CS to the culture medium revealed normal metabolism in these cells. An unaffected fetus was predicted on the basis of the cell feeding studies. The couple elected to abort this pregnancy, and studies on the fetus confirmed it would not have been affected with MLD.