Prenatal Diagnosis of Inborn Errors of Metabolism

Abstract

The evolution of the techniques aiming at the prenatal diagnosis of inborn metabolic disorders has closely reflected the progress in the knowledge of their underlying molecular defects. Initially, abnormal metabolites have been looked for in amniotic fluid. Recently, improved techniques of detection have permitted fast and reliable prenatal diagnoses through biochemical studies of cell-free amniotic fluid. Presently, the most widely used approach is the search for the defective gene product in cultured amniotic cells obtained through amniocentesis. Because of its relative safety, this procedure should be recommended, provided three prerequisites are met: a most accurate diagnosis of the index patient, the knowledge of the defective enzyme and its expression in cultured cells. For a correct interpretation of the results, cell culture parameters as well as specific activities of the mutant enzyme in the index case and the parental cells must be taken into account. Fetal blood sampling is a valuable alternative for some of the genetic disorders that cannot be detected in cultured amniocytes. The recently developed technique of chorion biopsy enables now to sample fetal cells during the first trimester of gestation. Meanwhile, the progress in DNA technology has uncovered exciting perspectives for the prenatal diagnosis of monogenic disorders at the gene level. Restriction endonuclease mapping has enabled to diagnose prenatally some forms of haemoglobinopathies, first through the polymorphism of sequences adjacent to the ß-globin gene, and now for the sickle-cell disease, by direct identification of the mutation.

Comparing amniotic fluid mass spectrometry assays and amniocyte gene analyses for the prenatal diagnosis of methylmalonic aciduria

“…15–20 mL of amniotic fluid was collected from each woman and centrifuged (3000 rpm, 5 min, 4°C). The cell-free amniotic fluid was then separated for biochemical assays, whereas amniocytes were cultured using standard methods for gene analyses [ 16 , 17 ].…”

First Trimester Maternal Serum Lysosomal Enzymes: Implications for Carrier Testing and Prenatal Diagnosis

“…The lysosomal storage diseases are progressive, and many are fatal in child hood or adolescence [2], Cultured amniotic fluid cells have been used extensively in the prenatal diagnosis of lysosomal storage dis eases [3][4][5][6]. However, amniocentesis is usually performed at 16 weeks and another 2-4 weeks are required for analysis.…”