First-trimester diagnosis of Menkes disease: intermediate copper values in chorionic villi from three affected male fetuses

Chorionic villus samples with copper contents of 1.91, 4.2, 5.6, and 6.3 ng/mg were observed in four cases with male karyotypes. These values were outside the range for unaffected males (0.30-0.85 ng/mg), and three of them were outside the control range (0.20-2.39 ng/mg). But these three values were below the values previously observed for affected Menkes fetuses (12.0-24.8 ng/mg). Follow-up by 64Cu uptake studies on the amniotic fluid cells was performed in three of these cases. A combination of 64Cu uptake and chase experiments on the amniotic fluid cells showed more convincingly than 64Cu uptake per se the direct copper values of 4.2 and 5.6 ng/mg to correspond to affected fetuses. Amniotic fluid cells from the male fetus with the CV copper value of 1.9 ng/mg showed normal results. The CV copper value of 6.3 ng/mg was considered pathognomonic for Menkes disease. The pregnancy was terminated, and the diagnosis was confirmed on fetal fibroblasts. Maternal deciduum prepared from the placentae showed in one of the cases with an affected fetus copper values ranging from 1.5 to 5.7 ng/mg. In six additional diagnostic cases, the copper content was determined in both CV samples and maternal deciduum. In three of these cases with normal CV sample copper, maternal decidua values of 4.85-7.8 ng/mg copper were observed. These results show that maternal deciduum contamination of a CV sample could cause a false-positive diagnosis.