First trimester diagnosis of methylmalonic aciduria

We have studied methylmalonyl CoA mutase activity in control chorionic villi to establish the potential use of assays performed directly on this tissue for prenatal diagnosis of methylmalonic aciduria. We report the detection of a fetus affected with the apo-mutase deficient form of this condition at 9 weeks' gestation. Methylmalonyl CoA mutase was markedly deficient in chorionic villi, approximately 2–5 per cent of the mean control value. However, incorporation of label from [¹⁴C]-propionate into protein was 10 and 40 per cent of the mean control value, respectively, in two portions of the same biopsy, highlighting potential problems in the use of this indirect assay. Normal results were obtained in chorionic villus samples from four other pregnancies ‘at risk’ for methylmalonic aciduria which were subsequently shown to be unaffected with this condition. The diagnosis in the affected pregnancy was confirmed by demonstration of a marked deficiency of methylmalonyl CoA mutase activity in villi obtained at termination and in cultured fetal fibroblasts. Reduced incorporation of [¹⁴C]-propionate label into protein was also found in these tissues.     

Maternal serum human chorionic gonadotrophin and pregnancy-associated plasma protein a,markers for fetal down syndrome at 8–14 weeks

Maternal serum levels of human chorionic gonadotrophin and its subunits (intact, α, and free βhCG) and pregnancy-associated plasma protein A (PAPP-A) were measured in 279 women between 8 and 14 weeks' gestation. This group included 23 pregnancies in which the fetus had Down syndrome (DS), diagnosed either at birth or during the second trimester (n=17) or from chorionic villus sampling (CVS) (n=6). Normal medians were determined from the 258 apparently normal pregnancies. The median levels of intact hCG (1·4 MOM) and free βhCG (2·1 MOM) were significantly raised, whereas the median level of PAPP-A (0·39 MOM) was significantly lower in the DS pregnancies when compared with the control group. Levels of αhCG were similar in both the control and the DS pregnancies. Analysis of samples taken prior to 14 weeks' gestation demonstrated that only PAPP-A (0·34 MOM) was significantly altered in DS pregnancies. However, after the exclusion of DS cases diagnosed at CVS, the median intact hCG (1·56 MOM), free βhCG (2·27 MOM), and αhCG (1·8 MOM) were all raised in DS pregnancies. This emphasizes the problem of the interpretation of biochemical markers when DS cases are diagnosed at CVS.     

Endocrine Disruptors in Mediterranean top marine predators

- DOI: http://dx.doi.org/10.1065/espr2006.01.018 Background, Aims and Scope Man-made Endocrine Disruptors (EDs) range across all continents and oceans. Some geographic areas are potentially more threatened than others: one of these is the Mediterranean Sea. Levels of some xenobiotics are much higher here than in other seas and oceans. In this paper we review the final results of a project in which the hypothesis that Mediterranean top predator species (such as large pelagic fish and marine mammals) are potentially at risk due to EDs was investigated. Methods In a four-year survey on the Mediterranean population of swordfish (Xiphias gladius), the potential toxicological effects of organochlorine compounds (OCs) on specimens of swordfish and tuna fish (Thunnus thynnus thynnus), caught in the spawning seasons from 1999 to 2002 in the Straits of Messina, Sicily (Italy), were investigated using vitellogenin (Vtg), Zona radiata proteins (Zrp), and cytochrome P4501A (CYP1A) activities (EROD, BPMO). Tissues (skin and blubber) were obtained from Stenella coeruleoalba, Tursiops truncatus, Delphinus delphis and Balaenoptera physalus from the western Ligurian Sea, between Corsica and the French-Italian coast, and Ionic Sea using biopsy darts launched with a crossbow. Benzo(á)pyrene monoxigenase (BPMO) activity was mesured in biopsies and cholrinated hydrocarbon levels were detected. Results and Discussion We illustrate the need to develop and apply sensitive methodological tools, such as biomarkers (Vitellogenin, Zona Radiata proteins and CYP1A activities) for evaluation of toxicological risk in Xiphias gladius and Thunnus thynnus thynnus), and nondestructive biomarkers (CYP1A activities and fibroblast cell culture in skin biopsy), for the hazard assessment of threatened marine mammals species (Stenella coeruleoalba, Tursiops truncatus, Delphinus delphis and Balaenoptera physalus) exposed to EDs. Conclusion The present research shows that: a) Vtg and Zrp can be used as diagnostic tools for fish stocks hazard assessment in the Mediterranean Sea; b) that CYP1A1 (BPMO) induction in cetaceans skin biopsy may be an early sign of exposure to EDs such as OCs and a potential alert for transgenerational effects. Recommendation and Outlook This research represents a warning signal of the potential reproductive alterations in marine top predators and suggest the need for continuous monitoring to avoid reductions in population and biodiversity in the Mediterranean Sea.     

A prospective cytogenetic study of third-trimester placentae in small-for-date but otherwise normal newborns

Data in the literature suggest that confined placental mosaicism might be associated with intrauterine growth retardation. However, this association may be coincidental and due to bias of ascertainment. We therefore started a prospective study based on the cytogenetic evaluation of placentae derived from growth-retarded newborns. We further minimized possible bias by excluding those small-for-date infants displaying findings which already could explain intrauterine growth retardation (mothers who are smokers, multiple pregnancies, gestosis, dysmorphic infants). In a collection of 71 small-for-gestational age newborns, we did not see a single case of true confined placental mosaicism.     

Prenatal diagnosis of atypical tay-sachs disease by chorionic villi sampling

We studied a family at risk for atypical TSD in which the index case showed, clinically, a late onset and a gradual psychomotor deterioration and biochemically, a residual hex. A activity in leucocytes. Two prenatal diagnoses of affected fetuses were made in this family, The first one on amniotic cells, the second one on trophoblast biopsy samples. Both of them were confirmed after abortion on cultured cells. Prenatal diagnosis of TSD, even of some atypical forms is possible using trophoblast biopsy, but formal confirmation should be obtained on cultured trophoblasts.