Answering a Question Older Than MostShawn E. McCandless, Pediatricians: MD What to Do About Duarte Variant “ ” In their articlePediatrics Developmental with careful selection of cutoff values, Outcomes in Duarte Galactosemia in1 identification of DG and other mild this issue of , Carlock et al variants can be significantly reduced report the results of a landmark study without missing cases of classic in which it was demonstrated that galactosemia. Duarte variant galactosemia (DG) is not associated with an increased risk of At present, in most places, the developmental abnormalities and does diagnostic evaluation of an abnormal not require dietary treatment. The NBS for galactosemia can take more field has been waiting 50 years for this than a week to result. The risk of Section of Genetics and Metabolism, Department of study, since (NBS) sepsis, hepatic injury, kernicterus, 2 and even death in infants with classic , School of , University of Colorado for galactosemia began. This work can Denver Anschutz Medical Campus, Aurora, Colorado be used to impact clinical care and NBS galactosemia leads most providers Opinions expressed in these commentaries are program planning. It can also be used to respond to an abnormal NBS result by stopping breastfeeding to those of the author and not necessarily those of the to teach us important lessons about the American Academy of Pediatrics or its Committees. use a galactose-free formula. The public funding of research into clinical addition of a DNA mutation screen DOI: https://​doi.​org/​10.​1542/​peds.​2018-​3292 outcomes and the importance of data- in the NBS laboratory for the Duarte Accepted for publication Oct 17, 2018 driven clinical decision-making. allele, or better yet, also including Address correspondence to Shawn E. McCandless, the several most common classic MD, Department of Pediatrics, University of The study was well designed and galactosemia mutations, could Colorado Denver AMC, 13121 E 17th Ave, L-28 Fourth robustly powered to answer the Floor, MS 8400, Aurora, CO 80045. E-mail: shawn. further reduce the number of infants questions asked, and the results [email protected] unnecessarily treated. Although clearly reveal through careful PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, the presence of the Duarte allele neuropsychological testing that 1098-4275). does not completely eliminate the no significant developmental Copyright © 2019 by the American Academy of risk of 2 severe mutations, it would differences are seen in children with Pediatrics provide reassurance, allowing health this biochemically mild variant of FINANCIAL DISCLOSURE: The author has indicated care providers to better assess the galactosemia, compared with controls. he has no financial relationships relevant to this need to stop breastfeeding without article to disclose. The immediate implication of this excessive risk to the infant. Most NBS FUNDING: No external funding. for health care providers is obvious; laboratories are now equipped to POTENTIAL CONFLICT OF INTEREST: The author has dietary , which always includes perform some level of DNA analysis on stopping breastfeeding, is not indicated indicated he has no potential conflicts of interest all samples to test for severe combined to disclose. for infants shown to have DG. Equally immunodeficiency, so this addition important, from a COMPANION PAPER: A companion to this article should not create an undue burden on can be found online at www.​pediatrics.​org/​cgi/​doi/​ perspective, the authors provide clear the laboratory. 10.​1542/​peds.​2018-​2516. and compelling evidence that NBS for DG is not useful, nor is it desirable. The authors of this work provide an To cite: McCandless SE. Answering a Question Thus, those states that have not important lesson when considering Older Than Most Pediatricians: What to Do About adjusted their NBS cutoffs to minimize new conditions for addition to NBS Duarte Variant Galactosemia. Pediatrics. 2019; the identification of infants with DG panels; unexpected variants are always 143(1):e20183292 should feel confident in doing so now. found, and reporting them may not Many states have already found that be free of harm to the child or family. Downloaded from www.aappublications.org/news by guest on September 26, 2021 PEDIATRICS Volume 143, number 1, January 2019:e20183292 COMMENTARY This has been true through the public funding specifically targeted by many potential intellectual biases, entire 55 years of NBS, beginning to answer simple, but critical, clinical both recognized and unrecognized, with the recognition of mild questions. The question asked and and tempered by the emotional hyperphenylalaninemia. Knowing answered here is of fundamental milieu associated with the events. this, it is no longer acceptable importance to providing high-quality As such, experience should not, and that the health care community and high-value health care, but it cannot, replace data and critical take 50 years to sort out whether does not have an associated reward analysis as the basis for clinical1 milder cases identified by NBS need that would lead the pharmaceutical decision-making. Carlock et al have treatment. Programs adding new or insurance industries to fund shown how it should be done in this conditions should feel a sense of nor does it deliver the innovative important article. obligation to take part in follow-up discovery potential desirable for ABBREVIATIONS studies to understand the natural funding through federal research history of the milder variants agencies or large philanthropic identified, and the addition of new organizations. Answering this DG: Duarte variant galactosemia disorders to NBS panels should be question required a unique funding NBS: newborn screening accompanied by prospective studies mechanism. This approach to funding designed to determine if treatment is a greatly needed contribution to REFERENCES of the milder variants is beneficial. clinical science. Children's health care providers must 1. Carlock G, Fischer ST, Lynch ME, et al. Developmental outcomes in demand this so that we never again Finally, it is intriguing that in 50 spend 50 years exposing infants to Duarte galactosemia. Pediatrics. years, competent and thoughtful 2019;143(1):e20182516 unneeded treatments that may not be clinicians routinely came to different 2. Beutler E, Irwin HR, Blumenfeld harmless. conclusions about the need for “ ” CM, Goldenburg EW, Day RW. Field intervention for DG on the basis of test of galactosemia screening In a more general sense, the results their experience. Experience should methods in newborn infants. JAMA. of this study, funded by the Patient- not be confused with fact. Experience 1967;199(7):501–503 Centered Outcomes Research is one way of understanding based Institute, validate the concept of on limited exposure to data, filtered

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Downloaded from www.aappublications.org/news by guest on September 26, 2021 Answering a Question Older Than Most Pediatricians: What to Do About Duarte Variant Galactosemia Shawn E. McCandless Pediatrics 2019;143; DOI: 10.1542/peds.2018-3292 originally published online December 28, 2018;

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