Mucolipidosis type IV: Accumulation of phospholipids and gangliosides in cultured amniotic cells. A tool for prenatal diagnosis

Cultured amniotic fluid cells from two mucolipidosis type IV (MLIV)-affected fetuses demonstrated accumulation of phospholipids and gangliosides when compared with normal controls. Like cultured skin fibroblasts from MLIV patients, cultured amniotic cells from the affected fetuses accumulated primarily lyso phospholipids and this could be demonstrated by radioactive labelling with appropriate precursors, either inorganic phosphate or oleic acid. Furthermore, like cultured skin fibroblasts, there was significant retention of exogenously supplied GDIA ganglioside in the affected amniotic cells. This storage was previously demonstrated to be unique to MLIV and thus can be used at present as a specific procedure for prenatal diagnosis of MLIV.     

Prenatal screening for haemoglobin disorders

The technology has been available to detect carriers of haemoglobin disorders since the late 1960s. Prenatal diagnosis has been available since 1978. First trimester diagnosis by chorionic villus sampling and DNA analysis was introduced in 1982, and subsequent simplifications in DNA technology have made screening, counselling and prenatal diagnosis cost-effective at the community level, in countries at all levels of development. Audit of prenatal diagnosis for haemoglobin disorders in countries which have the resources and infrastructure necessary for genetic population screening (such as the UK and other European countries), has shown that the number of prenatal diagnoses actually performed fall far short of expectation. The demonstration that this reflects failures in delivering information, screening and counselling to the populations at risk, rather than rejection of prenatal diagnosis, shows the importance of placing more emphasis on the organisational and social requirements for genetic population screening. In some countries current attitudes towards abortion exclude provision of prenatal diagnosis within the health service, but in many such cases it has been set up in the private sector. It is also being introduced through combined private and charitable efforts in an increasing number of developing countries, including some with extremely limited health resources: such centres are likely to act as nuclei for emergence of genetics services in these communities. A particularly notable recent achievement is the introduction of prenatal diagnosis in Nigeria, where 1–2% of all children born suffer from sickling disorders.     

Prenatal diagnosis of purine nucleoside phosphorylase deficiency in the first and second trimesters of pregnancy

Prenatal diagnosis was performed in two successive pregnancies of a mother with a previous child with purine nucleoside phosphorylase (PNP) deficiency. In one pregnancy, an affected fetus was diagnosed in the 18th week of gestation after the demonstration of PNP deficiency in cultured amniotic fluid cells. Also an abnormal purine nucleoside profile was found in the amniotic fluid. The diagnosis of an affected fetus was confirmed by the analysis of cultured fetal skin fibroblasts and placental villi. The complete deficiency of PNP activity in placental villi confirms that the prenatal diagnosis of this disorder is possible by the direct investigation of chorionic villi. In the subsequent pregnancy, a heterozygous fetus was predicted in the tenth week of pregnancy by using chorionic villi.     

Phenotypic analysis of fetal blood leucocytes: Potential for prenatal diagnosis of immunodeficiency disorders

Recent technological advances allow the detection and quantitation of subsets of leucocytes using monoclonal antibodies. We have taken advantage of this to study the ontogeny of fetal blood leucocytes, using very small blood samples obtained at fetoscopy. By 14 weeks gestation T cells represent 35 per cent or more of fetal leucocytes and the distribution of the helper/inducer and suppressor/cytotoxic subsets is similar to that of adults. B lymphocytes before 161/2 weeks are low (4–20 per cent), but rise to a mean of 28 per cent in 17–26 week fetuses. Granulocytic cells, many of which are phenotypically immature, represent 18–34 per cent of total leucocytes. The methodology employed is very reliable and offers the opportunity for the prenatal diagnosis of some immunodeficiency disorders, since using the same reagents we have diagnosed children with severe combined immunodeficiency shortly after birth.     

Prenatal diagnosis of fetal anomalies during the second trimester of pregnancy: Their characterization and delineation of defects in pregnancies at risk

During a follow-up study of 19 790 pregnancies at risk for a genetic disease, from 1968 to 1989, 1083 fetuses were found to have an anomaly during the second trimester, leading to 977 terminations of pregnancy. Neural tube defects (31.4 per cent), chromosomal disorders (27.1 per cent), and Mendelian or multifactorial diseases (10.6 per cent) were the main causes of fetal anomaly. More than half (52.9 per cent) of the fetal anomalies were detected by routine ultrasound examination. Forty-two per cent of cystic hygromas were secondary to a chromosomal defect. We stress the importance of a comprehensive fetal and newborn examination to ensure an accurate diagnosis so that subsequently accurate counselling can be provided.     

Prenatal diagnosis of inherited metabolic disorders by quantitation of characteristic metabolites in amniotic fluid: Facts and future

An attempt is made to summarize as completely as possible what is known about the prenatal diagnosis of amino– and organic acidurias by direct measurement of characteristic metabolites in amniotic fluid, and to indicate which disorders can potentially be diagnosed prenatally by direct quantitation of metabolites. Furthermore, the disorders are mentioned in which the prenatal diagnosis was proven to be unsuccessful by this approach. The prenatal diagnoses of a case of propionic acidemia and a case of tyrosinemia type I in the 11th and 12th week of gestational age, respectively, are reported and the prospects of performing amniocentesis in the first trimester for prenatal diagnosis are discussed.     

Prenatal diagnosis of inborn errors in peroxisomal β-oxidation

In recent years, an increasing number of inherited diseases in man have been recognized in which there is an impairment in the peroxisomal β-oxidation of very-long-chain fatty acids. In general, these disorders are associated with severe neurological and physical abnormalities and death within the first years of life. In this paper we describe our experience with regard to the prenatal diagnosis of a number of different inborn errors of peroxisomal β-oxidation. Eleven pregnancies at risk were monitored by measuring very-long-chain fatty acid levels as well as very-long-chain fatty acid β-oxidation in cultured chorionic villous fibroblasts and/or amniotic fluid cells. Five affected fetuses were identified. It is concluded that prenatal diagnosis in this group of diseases can be done reliably using cultured chorionic villous fibroblasts or amniotic fluid cells.     

Amniotic fluid pregnancy-specific β1-glycoprotein (SP1) in fetal developmental disorders

Concentration of pregnancy-specific β1-glycoprotein (SP1) was studied in second and third trimester amniotic fluid from pregnancies with various fetal developmental disorders. The material consisted of 26 cases with chromosomal disorders and 19 cases with nonchromosomal fetal malformations. The SP1 concentration was elevated in two cases of Meckel's syndrome (mean + 2.7–4.0 S.D.) as well as in one case of fetal triploidy (mean + 22 S.D.), while it was normal in all other 14 different fetal disorders.