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Aims: Gangliosides, i. e. sialic acid containing glycosphingolipids, constitute a major component of neuronal cells and are thought to be essential for brain function. UDP-glucose: ceramide glucosyl-transferase (Ugcg) catalyzes the initial step of glycosphingolipid (GSL) biosynthesis. A total deletion of the Ugcg-gene in mice led to embryonic lethality. In order to gain insight into the role of gangliosides in brain development and function, a cell specific disruption of Ugcg was performed., Methods: A cell specific disruption of Ugcg in mice was performed using the Cre/loxP-system. LoxP-flanked Ugcg-mice were generated and crossed with nestin-cre mice., Results: The nestin-promoted gene deletion in neuronal cells was indicated by the absence of virtually all gangliosides already at stage E15.5. Shortly after birth mice showed dysfunction of cerebellum and peripheral nerves, associated with structural defects. Axon-branching of Purkinje cells was significantly reduced. In primary cultures of neurons dendritic complexity was clearly diminished, while pruning occurred. Myelin sheaths of peripheral nerves were broadened and focally severely disorganized. GSL deficiency also led to a downregulation of gene expression sets involved in brain development and homeostasis. Mice died approximately 3 weeks after birth., Conclusions: The pronounced neurologic symptoms in postnatal mice with neuronal specific deficiency of glucosylceramide synthesis demonstrate that GlcCer-derived GSL may not serve functions essential for early brain development. They are, however, required for neuron differentiation and brain maturation.

We have offered the so-called "triple-marker screening" since May 1991 to all patients who came for prenatal care and did not select an invasive procedure primarily. First evaluation of 5210 cases revealed that 3.7% were test-positive for neural tube defects, 13.8% for Down's syndrome and 0.5% for both at the same time. The explanation for the comparatively high "test-positive" rate of 13.5% is the maternal age distribution with the median at 31.4 years. The highest number of women selecting triple-marker determinations was in the age group of 35 years. We detected 16 cases of Down's syndrome and in this group the majority of women was below 35 years. The decision of women to have an invasive procedure was obviously very much influenced by the actual risk assessment, because amniocentesis was chosen by 72/85 (84.8%) of women with a risk of more than 1:50, 192/290 (66.2%) of women in the risk category of 1:51 to 1:200 and 182/333 (54.6%) in the risk category of 1:201 to 1:400. The follow-up is not yet complete, but there is already good evidence for the efficiency of the screening program. Triple-marker screening also proved predictive in 10 cases of trisomy 18 and 8 cases of triploidy in this series. As a cut-off value we chose the risk of 1:386 which is equivalent to the odds of a 35 year old to have a child with Down's syndrome at birth.(ABSTRACT TRUNCATED AT 250 WORDS)

7000 pregnancies were analysed after genetic amniocentesis in respect of the further course and results of prenatal diagnosis (observation period 1975-1988). In 3.1% (217 cases) samples of amniotic fluid were discoloured. Vaginal haemorrhages prior to amniocentesis were recorded with significantly higher incidence (18%) in patients with discoloured amniotic fluid than in a control group (n = 217) with normal colour of the amniotic fluid (4.6%) (p less than 0.001). Miscarriages and chromosome anomalies occurred more often in the study group (3.7%/2.8%, control group: 0.9%/1.8%, n.s.). The risk of miscarriages was increased in cases with sanguineous amniotic fluid if the amniotic fluid alpha-fetoprotein values were enhanced at the same time. Significant differences were observed in respect of the incidence of foetal malformations in patients with discoloured amniotic fluid (7.8%) and in the control group (2.3%) (p less than 0.01). Borderline or definitely pathological amniotic fluid AFP concentrations were found often if the amniotic fluid was discoloured (6.9%, control group 3.2%). If discoloured amniotic fluid was sampled, foetal malformations should be excluded sonographically. In 82% of all cases with discoloured amniotic fluid and foetal malformations pathological sonographic findings and/or enhanced MS-AFP values were recorded even prior to amniocentesis.

If, in twin pregnancy, one twin shows severe malformation, the question arises as to how the other twin can remain unaffected. For the purpose of ensuring the diagnosis in case of suspected neural tube defect, the main diagnostic tools are sonography, biochemical methods of alpha-fetoprotein determination and acetyl cholinesterase activity, as well as cell-morphological identification of so-called "rapidly adhering cells". Parents and obstetricians face a difficult decision when confronted by the possibilities of maintaining pregnancy or of induced abortion after diagnosis of a malformed and a healthy twin. The case of a severe discordant cranial malformation is described on the basis of a case report. The diagnostic and therapeutic problems are discussed.