Quantitative assays of enzyme activity in single cells: early prenatal diagnosis of genetic disorders

The combined use of special cell culture techniques and biochemical ultramicromethods permits one to handle very small amounts of materials, to reduce the costs of chemicals, and more accurately to assess gene dosage effects by expressing enzyme activities per cell instead of per total cell protein. An alkaline phosphatase induction test has been developed which allows one to screen small numbers of fibroblasts for lysosomal storage diseases, cystic fibrosis, and chromosomal disorders. A successful attempt has been made to automate the microtechniques. Combining the alkaline phosphatase induction with the ultramicro automatization should eventually permit one to screen all pregnancies for major possible fetal genetic defects. Automated ultramicro enzyme assays should contribute to the general development of clinical chemistry.