Lab Matters Spring 2019 - Page 8

FEATURE “The easy disorders have already been done” Currently, virtually all of the four million or so babies born in the United States each year receive NBS within the first 24 to 48 hours of life. Since 97% of this screening is the responsibility of state public health laboratories (PHLs), PHL scientists have spearheaded the implementation of new screening technologies and generally embraced the expansion of screening panels. But as NBS candidate disorders become rarer and rarer, their diagnosis less clear-cut, and their treatments less effective, NBS advocates have grappled with what Michele Caggana, ScD, FACMG, calls the “push and pull of adding new conditions.” Caggana, who heads the NBS Program and the Genetic Testing Quality Assurance Program at New York’s Wadsworth Center—the state PHL—said, “New York has always been an early adopter” of NBS candidate conditions, just last year adding SMA, mucopolysaccharidosis Type I (MPS-I) and guanidinoacetate methyltransferase deficiency to its screening panel. Yet, she said, “We have to be thoughtful about how we do NBS expansion. The low hanging fruit, the easy disorders, have already been done.” One unresolved issue, said Patrick Hopkins, the semi-retired former NBS chief at the Missouri State Public Health Laboratory, is the “growing challenge of deciding on what we’re screening for, such as newborn disorders, childhood disorders and late onset disorders. Often we cannot safely sort out the difference between these on the screening test, and if we could, where would we draw the line?” Pompe disease, for example, has a classic infantile form, requiring immediate intervention, and later onset forms (about 72% of cases) in which serious symptoms may be delayed until adulthood. Babies with either of these variants will screen positive for Pompe, as well as babies with a less-urgent, non-classic infantile form and babies with pseudo-deficiency, who have biochemical Pompe disease markers, but will never go on to develop the disease. Follow-up providers must determine the appropriate diagnosis and counsel families based on limited clinical guidance, since there is little medical experience with Pompe, especially over the long term. Molecular testing raises similar issues. Now used for discrete NBS applications— mostly second or third tier testing—it is expected to become more prominent in the NBS laboratory. Said Caggana, “What we’re seeing with molecular [technology]—the ability to multiplex and look at several different genes at once—harkens back to when mass spectrometry came on the scene [in the early 2000s].... It really pushed the field.” Yet molecular testing comes with its own challenges, including the need for added infrastructure (including new instrumentation, a dedicated “clean” room and space to accommodate a unidirectional flow of testing), highly specialized staff training and capacity to analyze massive amounts of genetic data. Moreover, Caggana noted that “no one’s assessed molecular [findings] on a broad stroke of the population of healthy babies” to inform data analysis and interpretation of novel gene variants. Kimberly Noble Piper, RN, CPH, CPHG, genetics coordinator for the Iowa Department of Public Health (IDPH) said molecular screening “comes with a Babies Saved Here: Patrick Hopkins and Mark Temple in the Missouri LSD Testing Laboratory. Photo: MO PHL 6 LAB MATTERS Spring 2019 PublicHealthLabs @APHL