HUM-MOLGEN archive: DIAG: 2 messages: "the future of genetic newborn screening",

************************************************************** HUM-MOLGEN DIAGnostics/Clinical Research ************************************************************** This DIAG message contains submessage(s): 1) The future of newborn screening, From: "Brian Mannix (mmatrix)" <BMannix@AOL.COM> + a comment from the editor 2) Asian DNAs Carlo Gambacorti MD, Editor, Human Molecular Genetics network Diagnostics/Clinical Research Section ************************************************************** ************************************************************** I would like to stimulate some discussion on the ways that genetic technology may be used to improve newborn metabolic screening programs. (for PKU, galactosemia, maple syrup urine disease, etc.). I offer the following rough protocol for comment. 1) At birth, the physician recovers as much cord blood as possible and sends it to a lab. 2) The lab uses genetic probes to test for the usual metabolic disorders, as well as other common genetic errors (e.g., CF). 3) Samples that test normal are discarded; samples that test positive are transformed to contain the appropriate normal alleles. 4) The transformed cells are transfused back into the infant to provide some nominal level of enzyme activity. Since cord blood contains stem cells, this enzyme activity could, in principle, last a lifetime. Compared to today's technology, such a protocol would provide faster and more accurate diagnoses, could be expanded to many more birth defects, and could provide a possible therapeutic benefit. On the other hand, there are some obvious disadvantages as well. The protocol above would always be more expensive than today's screening tests, if only because of the volume of blood involved. Moreover, while using cord blood may save the infant a heel stick, it is hardly convenient: there is a lot going on during a typical birth that is more urgent than collecting a screening sample. And, of course, it may turn out that very few genetic diseases would benefit from a simple transfusion of transformed stem cells. Because of these shortcomings, such as system might be used, at best, only on a subset of diseases for a subset of at-risk births. Nonetheless, I think it is useful to speculate along these lines, and I welcome any and all comments. Brian Mannix Bmannix@aol.com EDITOR'S NOTE This is enticing and intriguing message and should be read for what it is. Several items must be considered when reading it: - genetic tests are not yet available for many inherited diseases, and therefore the possibilities to correct the defect are not therefore available; - since the results of the tests are not immediate, it would need to store many samples, with a very significant cost (a sensitive item today, who should pay for ?); - the correction is not guaranteed by the transformed cells. Some diseases (like CF) are unlikely to be affected by the infusion of cord blood cells, in addition there is no proof at present that these cells will persist for a long term; they can be immunologically rejected (because of the new viral and cellular genes intro duced). The transplant, even if autologous, would require a certain degree of immunosuppression of the host, and therefore would carry its own burden of toxicity and risk. Mass collection of cord blood seems also problematic; an alternative could be to carry it out in selected cases (carrier families, prenatal diagnosis...). Carlo Gambacorti MD ************************************************************** We have recently identified a highly polymorphic Y chromosome marker and are currently genotyping it on Caucasian, African-American and American Indian DNAs. We would also like to genotype it on a comparable collection of Asian DNAs. If anyone has such a collection and is interested in collaborating please get in touch with me. Don Bowden Bowman Gray School of Medicine Winston-Salem, NC Donald Bowden <BOWDEN@MGRP.BGSM.WFU.EDU>