www.elsevier.com/locate/ymgme

Molecular Genetics and Metabolism 91 (2007) 303–304

Conference Report

Third Robert Guthrie Memorial Lecture

The Third Robert Guthrie Memorial Lecture, ‘‘Who IsAfraid of MS/MS? Myths and Challenges of ExpandedNewborn Screening,’’ took place on March 26, 2007, atthe Society for Inherited Metabolic Disorders nationalmeeting in Nashville, Tennessee. The speaker was Piero Ri-naldo, M.D., Ph.D., T. Denny Sanford Professor of Pedi-atrics and Professor of Laboratory Medicine at the MayoClinic College of Medicine, Rochester, Minnesota(Fig. 1). Dr. Rinaldo was a most appropriate speaker forproviding an update on the status of fast-paced events sur-rounding expanded newborn screening. His current focus ison the expansion and quality improvement of newbornscreening programs worldwide. He has been very activein coordinating the Regional Collaborative Project for lab-oratory quality improvement of newborn screening by tan-dem mass spectrometry with more than 60 activeparticipants worldwide. He is also a member of the HHSSecretary Advisory Committee for Heritable Disorders inNewborns and Children.

The March 26th event was the first time the memoriallecture has been given at a national meeting and it provedto be a resounding success. There were 275 guests in theballroom of the Nashville Renaissance Hotel for the com-bined luncheon and lecture. Both the first and secondGuthrie Memorial lecturers, Dr. Edwin Naylor (1997)and Dr. Harvey Levy (2000), were present.

The lecture itself was both informative and entertaining,with many anecdotal slides and memorable commentsabout Robert Guthrie (Fig. 2) and his contributions tonewborn screening by people who knew him well, includingHarry Hannon, Rodney Howell, Harvey Levy, EdwinNaylor, and Kenneth Pass. The status of newborn screen-ing in the US since 2000 was presented, including the ad-vent of tandem mass spectrometry (MS/MS) and theadded complexities associated with the adoption of ex-panded newborn screening state by state without na-tional-level newborn screening standards. The variance inresources available to individual states for the developmentof screening methodologies; each program’s interpretationof available evidence concerning given conditions; and thelevel of public advocacy by families, health care profession-

doi:10.1016/j.ymgme.2007.05.016

als, or state legislators have all contributed to divergenceamong states regarding which conditions should be man-dated for newborn screening. In response to the lack ofnewborn screening program uniformity, Dr. Rinaldo ex-plained that the Maternal and Child Health Bureau(MCHB) of the Health Resources and Services Adminis-tration (HRSA), commissioned the American College ofGenetics (ACMG) to outline a process of standardizationof outcomes and guidelines for state newborn screeningprograms and to define responsibilities for collecting andevaluating outcome data, including a recommended uni-form panel of conditions to include in state newbornscreening programs. The resulting HRSA/ACMG UniformScreening Panel (2005) consists of 29 primary conditions,20 of which are detected by MS/MS, and 25 secondary tar-gets, 22 of which are detected by MS/MS. This represents ahuge expansion from the up to 10 disorders evaluated bynewborn screening in 2000.

In the discussion ‘‘Who Is afraid of MS/MS?’’ Dr. Ri-naldo gave examples of the associated fears. These includedthe fear of patients being left behind; the fear of new tech-nologies and expansion in the face of budget cuts; the lossof control and revenue; the definition of ‘‘missed’’ cases;and the issue of too many false positives. Also discussedwere the myths surrounding newborn screening, such asthe concern that expanded screening by MS/MS wouldcause ‘‘too many’’ false positive cases. One of the purposesof the Regional Collaborative Project is to regularly mon-itor the false positive rates and continually fine-tune theassociated cutoffs for individual analytes. A second mythis that MS/MS is suitable for the uniform panel but notfor the secondary targets. As it turns out, only two of thesecondary targets are unrelated to the differential diagnosisof a condition on the uniform panel. Other myths includedthe misnomer that newborn screening data are not compa-rable from lab to lab and that inter-laboratory comparisonis not possible. These were all proven wrong by thespeaker.

Among the challenges and opportunities mentionedthat surround expanded newborn screening was the factthat screening labs do not collaborate enough. Increased

Fig. 2. Robert Guthrie.Fig. 1. Piero Rinaldo.

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collaboration could answer questions such as ‘‘do we needto collect a second specimen?’’ Consistent and objectiveperformance metrics could be developed. Screening labora-tories could come together to prove the clinical utility andcost benefits of second tier testing. These are all among theissues that the HRSA-funded Regional Collaborative Pro-ject is currently addressing. In fact, there is a monthly dis-tribution of tools and reports to its members, which arerepresented by 23 international laboratories and 33 statelaboratories. Why not find out if your state is a member?If not, find out why not. This is one organization that rep-resents a win–win scenario for babies born in the US.

My heartfelt thanks go to Piero Rinaldo for providingan authoritative and state-of-the-art review of expandednewborn screening in the US and to the Society for Inher-ited Metabolic Disorders for hosting the Third RobertGuthrie Memorial Lecture.

Georgirene D. VladutiuProgram Chair

The Society for Inherited Metabolic Disorders

Annual Meeting, 2007