Diagnosis of placental sulfatase deficiency.

Placental sulfatase deficiency has been found in four pregnancies (cases 1 to 4) with inappropriately low levels of urinary estriol excretion (less than 1.3 mg. per day near term gestation) associated with healthy neonates. The basis of the diagnosis in these cases was the greatly limited capacities for hydrolysis of 14C-dehydroepiandrosterone sulfate (DHA-S) and 3H-estrone sulfate (0.2 mugCi each) to the free steroids during incubation of placental homogenates. Placental aromatase activities in vitro for free DHA and the concentrations of appropriate estrogen precursors in cord blood were normal or elevated. The defect was diagnosed prenatally in two of these cases on the basis of failure to increase the maternal excretion of urinary estriol (0.6 to 0.7 and 1.3 to 1.3 mg. per day, respectively) following acute instillation of DHA-S (250 mg.) into the amniotic fluid and on normal levels of estrogen precursors in cord blood. In comparison, a twofold increase in maternal estriol excretion was observed after infusing DHA-S into the amniotic cavity of a "high-risk" pregnancy having normal sulfatase and aromatase activities in vitro (case 5). These enzyme activities were also found to be similarly normal in another placenta from an undergrown fetus (case 6) and in six normal placentas. The clinical features of these pregnancies, the first ones described from the western hemisphere, are similar to reported cases: the newborn progeny are healthy males who appear to be developing normally. The prenatal diagnosis of the sex-specific placental enzyme defect has been made possible by the use of an intra-amniotic DHA-S loading test.