Serum lipid,apolipoprotein and lipoparticle levels in the human fetus

Blood collected from 62 fetuses aged 20–38 weeks of gestation was studied. The values of ten lipid parameters were determined: cholesterol (TC), triglycerides (TGs), apolipoprotein Al (apo A1), apolipoprotein B (apo B), apolipoprotein E (apo E), total apolipoprotein CIII (apo CIII), apolipoprotein CIII present in particles containing apo B (apo CIII LpB) or not (apo CIII Lp non-B), lipoparticles A1 (LpA1), and lipoprotein a (Lp(a)). The results show that, except for apo E, all the studied parameters were present in lower concentrations than in adults and newborns, and that Lp(a) is not detectable at that stage in life.     

A simple,rapid, and highly informative PCR-based procedure for prenatal diagnosis and carrier screening of phenylketonuria

The polymorphic information content (PIC) and the degree of heterozygosity of several polymorphic systems within the phenylalanine hydroxylase (PAH) gene were determined in 85 European Caucasian and 19 Chinese phenylketonuria (PKU) kindreds. The first system examined, a short tandem repeat (STR), had a PIC of 80 and 73 per cent in these Caucasian and Chinese samples, respectively. The degree of heterozygosity actually observed for this system was 81 and 64 per cent in the Caucasian and Chinese PKU families, respectively. Through the addition of a second polymorphism based on a variable number of tandem repeats (VNTR), the PIC was increased to 90 per cent in Caucasians, but only to 75 per cent in Chinese. The degree of heterozygosity observed for this combination was 94 per cent in European PKU families and 67 per cent in Chinese PKU families. The further addition of an Xmnl RFLP increased both the PIC and the level of heterozygosity in Caucasians to 95 per cent, but did not change either of these measures in Chinese. The combined use of these three polymorphisms significantly increases the informativity of prenatal diagnostic and carrier screening procedures in both Caucasian and Chinese PKU kindreds. Furthermore, since each of these polymorphisms can be studied by PCR-based methods, these new tests can be performed more quickly and easily than previous Southern-based procedures.     

Adjustment formulae for maternal serum alpha-fetoprotein,human chorionic gonadotropin,and unconjugated oestriol to maternal weight and smoking

Serum levels of alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), and un-conjugated oestriol (uE3) were measured in serum samples of 4131 non-smoking and 1018 smoking women during the second trimester of pregnancy. The levels of all three analytes decreased with increasing body weight. The AFP median was significantly increased in smokers in a dose-response association; hCG decreased by 21 per cent and uE3 decreased by 3 per cent in smokers in a non-dose-related fashion. Regression functions for adjustment of serum levels for weight and smoking should be considered in risk estimation for Down syndrome in order to give a woman's individual risk more precisely.     

Mutation analysis for prenatal diagnosis and heterozygote detection of Gaucher disease type III (norrbottnian type)

A single base substitution in exon 10 of the glucocerebrosidase gene was detected in families affected by Gaucher disease (GD) type III. This mutation, which results in the substitution of proline for leucine in position 444 of glucocerebrosidase, has been shown to result in type III GD in a Swedish population. Three fetuses at risk for GD type III were diagnosed as homozygous for the mutation and the pregnancies were terminated. In a fourth pregnancy, one parent was excluded as being a carrier and the risk of having a child affected by GD was ignored. Direct analysis of common mutations causal to GD is now available and improves prenatal diagnosis in families where the molecular defect has been characterized.     

Immunocytochemical localization of peroxisomal β-oxidation enzymes in human fetal liver

In the majority of congenital peroxisomal disorders, β-oxidation of very long chain fatty acids is deficient. We have investigated the appearance and localization of the three peroxisomal β-oxidation enzymes in normal fetal liver (fertilization age between 5 and 18 weeks) with protein A- gold immunocytochemistry and silver enhancement for light microscopic visualization. With specificity-tested polyclonal antibodies, acyl-CoA-oxidase, bifunctiooal enzyme, and 3-oxoacyl-CoA thiolase were localized in the peroxisomes of the parenchymal cells, which appear as brown or black granules. In the youngest specimen, no immunopositive reaction was obtained. A weak reaction with anti-thiolase was obtained at the age of 6–7 weeks. At a fertilization age of 8 weeks, peroxisomes could be distinctly visualized after immunostaining for all three enzymes. From a staining series with anti-thiolase on simultaneously treated slides, it appears that the amount of antigen per peroxisome and the organelle size increase between the seventh and eighteenth weeks. These data should enable a more specific diagnosis in fetal liver biopsies from pregnancies at risk and after termination of pregnancy.     

Blood chemistry of human fetuses in the second and third trimesters

Six biochemical parameters and four enzyme activities were determined from the serum of 76 healthy and 56 pathological human fetuses between the 20th and 38th week of pregnancy. In the normal fetuses studied within that period, creatinine, immunoglobulin M, lactate dehydrogenase, and gamma-glutamyltransferase increased; haemoglobin F and glucose progressively decreased; and alkaline phosphatase was at a peak around the 26th week; cholesterol and triglycerides were always low. The same parameters were also measured in some of the pathological fetuses and compared with their normal counterparts.     

Bilateral renal agenesis in three consecutive siblings

We report here an unusual recurrence of bilateral renal agenesis (BRA) in three consecutive siblings. Chromosome analysis was normal, as were renal ultrasound studies on both parents and their surviving child. Ultrasound was employed prenatally to diagnose Potter's syndrome in both of the recurrences, and autopsy confirmed BRA in otherwise normal fetuses. Recurrence of BRA points to the usefulness of ultrasound in monitoring subsequent pregnancies in couples who have had one such occurrence. Ultrasound studies should also be performed in non-affected family members to detect the presence of asymptomatic anomalies of the genitourinary system, but a negative family study does not preclude recurrence of BRA.     

Estimation of the weight of chorionic villus samples obtained from first trimester pregnancies by transcervical aspiration

Eight obstetricians experienced in chorionic villus sampling were asked to estimate the weight of samples of villi with and without a reference photograph. Referral to the photograph significantly improved the accuracy of their estimations.     

Prenatal diagnosis of the infantile type of neuronal ceroid lipofuscinosis by electron microscopic investigation of human chorionic villi

Chorionic villus biopsy specimens were studied electron microscopically in six pregnancies at risk of the infantile type of neuronal ceroid lipofuscinosis (INCL). The biopsy was performed in all cases in the first trimester of pregnancy (8–10 gestation weeks) by the transcervical route. In one case, the biopsy was repeated at 17 weeks by the transabdominal procedure. In two pregnancies, the endothelial cells and, to a lesser extent, the mesenchymal cells of the chorionic villi contained unit membrane-bound inclusions typical of INCL. In both cases, the pregnancy was terminated and in one of them identical inclusions were found in the brains and kidneys of the fetus at 20 weeks of gestational age. The children from the remaining four pregnancies are healthy and have shown no signs of the disease.