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Citrullinaemia was presumed to be excluded in a fetus at risk by the direct assay of argininosuccinate synthetase in chorionic villi. The diagnosis was confirmed after amniocentesis by normal argininosuccinate synthetase activity in the cultured amniotic fluid cells and by a normal citrulline concentration in the amniotic fluid. The prediction of a normal fetus was confirmed at term by the birth of a non-citrullinaemic boy.

We describe our experience in prenatal diagnosis of six foetuses at risk for galactosaemia. In one family the parents were both shown to be double heterozygotes at the galactose 1-phosphate uridyl transferase (Gal-PUT) locus, the mother having a Duarte/Los Angeles and the father a Duarte/galactosaemia genotype. The foetus (and an older brother previously thought to have classical galactosaemia) was also a Duarte/galactosaemia double heterozygote. In the other five families, the parents and three foetuses were heterozygous carriers of the galactosaemia gene, one of the foetuses had galactosaemia, and one was homozygous for the normal gene. It is concluded that by a combination of family studies and assay of cultured amniotic cell Gal-PUT, accurate prediction of the foetal Gal-PUT genotype is now possible.

Argininosuccinate synthetase activity in amniotic fluid cells from a fetus at risk for citrullinaemia was low compared to the activity in amniotic fluid cells from a normal fetus, but five times the activity in fibroblasts from a patient with citrullinaemia. These enzyme values indicated indicated a normal or heterozygous fetus. Chromosome analysis of the amniotic fluid cells from the fetus at risk, however, showed an unusual X/20 translocation. As we could not guarantee the delivery of a normal child, the parents chose to have a therapeutic abortion. Argininosuccinate synthetase activity in the liver and kidney of the aborted fetus was in the normal and heterozygous range respectively, confirming the prenatal diagnosis. The activity in the father's fibroblasts was low, less than 10% of normal. The difficulty of interpreting the results of prenatal diagnosis in such a family and the importance of studying parental cells are discussed.

Normal amniocytes and chorionic villous cells in culture are able to produce 14CO2 from exogenous [1-14C] phytanic acid. In contrast, cells from four fetuses at risk for the cerebro-hepato-renal (Zellweger) syndrome and related disorders showed a greatly reduced activity, indicating a block in oxidation of the fatty acid. Our data confirm that phytanic acid oxidase activity measurement can be used for the prenatal assessment of this group of disorders.