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Biochemical Assays for Metabolic Diseases

المؤلف:  Cohn, R. D., Scherer, S. W., & Hamosh, A.

المصدر:  Thompson & Thompson Genetics and Genomics in Medicine

الجزء والصفحة:  9th E, P403

2026-03-08

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 Although any disorder for which the genetic basis and responsible genetic variant(s) are known can be diagnosed prenatally by DNA analysis, more than 100 metabolic disorders can also be diagnosed by biochemical analysis of chorionic villus tissue or cultured amniotic fluid cells. A few rare conditions can even be identified directly by assaying a substance in amniotic fluid. Most metabolic disorders are rare in the general population but have a high recurrence risk since most are autosomal recessive conditions. Because each condition is rare, the experience of the laboratory performing the prenatal diagnostic testing is important and it should be done at specialized centers. Whenever possible, a biochemical assay on directly sampled chorionic villus tissue (as opposed to cultures) is preferred to avoid misinterpretation of results due to the expansion in culture of contaminating maternal cells. Access to a cultured cell line from an affected individual in the family is highly advisable so that the laboratory can confirm its ability to detect the biochemical abnormality in the proband before the assay is attempted in CVS or amniotic fluid cells from the pregnancy at risk. Many metabolic disorders cannot be diagnosed prenatally by enzyme assays because the enzyme is not expressed in amniocytes or chorionic villi or a reliable biochemical assay is not available. For these, DNA sequencing should be performed.

Biochemical tests have one advantage over DNA: they can detect abnormalities caused by any mutant allele that has a significant effect on the protein function. This is particularly significant for disorders with a high degree of allelic heterogeneity, genes in which pathogenic variants occur in regions that are not routinely sequenced, or by a high proportion of new mutations. In addition, biochemical testing may be the only option for prenatal diagnosis if the causative mutations in the family are unknown.