Biochemical and Biologic Problems and Pitfalls in the Prenatal Diagnosis of Inborn Errors of Metabolism

Abstract

Rapid expansion of our knowledge of the biochemical basis of inherited metabolic disorders during recent years and the development of new diagnostic methods have led to rapid advances in the intrauterine diagnosis of the inborn errors of metabolism. Amniocentesis continues to be the primary tool. Cell-free amniotic fluid, noncultivated amniotic fluid cells, and cultivated amniotic fluid cells have all been utilized in the prenatal diagnosis of inborn errors of metabolism, and, given the appropriate circumstances, each may provide important information regarding the status of the fetus. The accuracy of prenatal biochemical diagnosis has generally been very high, but errors have occurred. It is of paramount importance that extreme caution be exercised in the interpretation of prenatal studies. In many instances, a decision as to whether or not a pregnancy will be continued is based on the result of a single laboratory study. The responsibility entrusted to those involved in prenatal diagnostic studies is therefore great. It is essential that everyone involved in such endeavors be thoroughly familiar with the origin and characteristics of normal amniotic fluid and amniotic fluid cells. The normal variability in any biochemical or cytological characteristic must be well defined before the results obtained from a particular analysis can be assumed to represent fetal abnormality.