SUPPLEMENT ARTICLE Naming and Counting Disorders (Conditions) Included in Newborn Screening Panels Lawrence Sweetman, PhDa, David S. Millington, PhDb, Bradford L. Therrell, PhDc, W. Harry Hannon, PhDd, Bradley Popovich, PhDe, Michael S. Watson, PhDf, Marie Y. Mann, MD, MPHg, Michele A. Lloyd-Puryear, MD, PhDg, Peter C. van Dyck, MD, MPHg aInstitute of Metabolic Disease, Baylor University Medical Center, Dallas, Texas; bBiochemical Genetics Laboratory, Duke University, Research Triangle Park, North Carolina; cNational Newborn Screening and Genetics Resource Center, Austin, Texas; dNewborn Screening Branch, Centers for Disease Control and Prevention, Atlanta, Georgia; eSirius Genomics Inc, Vancouver, British Columbia, Canada; fAmerican College of Medical Genetics, Washington, DC; gMaternal and Child Health Bureau, Health Resources and Services Administration, Washington, DC The authors have indicated they have no financial relationships relevant to this article to disclose. ABSTRACT The rapid introduction of new technologies for newborn screening is affecting decisions about the disorders (conditions) that are required or offered as an option through public and private newborn screening. An American College of Medical www.pediatrics.org/cgi/doi/10.1542/ peds.2005-2633J Genetics report to the Health Resources and Services Administration summarized doi:10.1542/peds.2005-2633J an extensive effort by a group of experts, with diverse expertise within the The opinions stated herein are those of the newborn screening system, to determine a process for selecting a uniform panel of authors and not necessarily those of the newborn screening disorders. The expert panel did not propose a mechanism for Centers for Disease Control and Prevention, the Health Resources and Services counting or naming conditions. Differences in the nomenclature used to identify Administration, or the Department of disorders have resulted in difficulties in developing a consensus listing and count- Health and Human Services. ing scheme for the disorders in the recommended uniform panel. We suggest a Key Words system of nomenclature that correlates the screening panel of disorders recom- newborn screening, disorders, nomenclature mended in the American College of Medical Genetics report with the screening Abbreviations analyte and accepted standardized nomenclature. This nomenclature system is ACMG—American College of Medical proposed to remove ambiguity and to increase national uniformity in naming and Genetics MS/MS—tandem mass spectrometry counting screening disorders. Accepted for publication Dec 27, 2005 Address correspondence to Lawrence Sweetman, PhD, Institute of Metabolic Disease, Baylor Research Institute, 3812 Elm St, Dallas, TX 75226. E-mail: [email protected] . PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275); published in the public domain by the American Academy of Pediatrics S308 PEDIATRICS Volume 117, Number 5, May 2006 Downloaded from www.aappublications.org/news by guest on September 30, 2021 HE RAPID INTRODUCTION of new technologies for ferent analyte, from which more information can be Tnewborn screening is affecting decisions about the obtained to improve the overall identification process. In disorders (conditions) that are required or offered as an most cases, newborn screening involves a single analysis option through public and private newborn screening. that detects a single marker; in recent years, however, There is general agreement that it is preferable to have a newer technologies have allowed for the simultaneous uniform panel of disorders required and offered nation- detection of multiple analytes through a single analytical wide, rather than the variability among programs that process. In newborn screening, multianalyte analyses exists currently. To provide direction for national uni- have included flow chemical assays for some metabolic formity, the American College of Medical Genetics conditions, electrophoretic and chromatographic assays (ACMG)1 recently recommended a decision-making for hemoglobinopathies, and, more recently, MS/MS as- process and a resultant core panel of disorders to be says for metabolic conditions. Because of the ability of considered for adoption and implementation by all US MS/MS to detect markers that may identify Ͼ1 disorder, newborn screening programs. naming and counting the disorders associated with Differences in the nomenclature used to identify dis- MS/MS technology have been particularly challenging. orders, sometimes confounded by multiple clinical vari- The primary analytes detected through MS/MS new- ations, have resulted in difficulties in developing a con- born screening and the associated disorders are listed in sensus listing and counting scheme for the disorders in Tables 1 and 2, which illustrate the potential breadth of the recommended uniform panel. For example, confu- the naming and counting difficulties. Perhaps the sim- sion results from choosing either the name of the disor- plest description of the spectrum of disorders detectable der, the name of the analyte deficiency, or the name of through MS/MS newborn screening, which identifies the screening analytes in a nonsystematic way. Counting multiple amino acid and acylcarnitine analytes, is the disorders creates even more confusion, because multiple phrase “MS/MS-detectable disorders of amino acid, or- variations of a disorder sometimes are counted in differ- ganic acid, and fatty acid metabolism.” However, many, ent ways or are not counted at all. The naming and including some physicians, legislators, and parents, seem counting problem is especially apparent with multiana- to prefer a specific list of newborn screening disorders. lyte test systems, such as tandem mass spectrometry As a consequence, there has been a competition among (MS/MS) tests for biochemical disorders, that detect si- screening programs (public and private) to offer the multaneously large numbers of different analytes (and largest number of screening disorders. To some extent, therefore disorders) in a single assay from a single dried this has been driven by the consumer perception that blood spot punch.2,3 more is better. Therefore, whereas some newborn We suggest a system of nomenclature that correlates screening programs report screening panels that detect the screening panel of disorders recommended in the 25 to 35 disorders,4,5 others report detecting Ͼ50 disor- ACMG report with the screening analytes and accepted ders6 by using similar systems and screening for the same standardized nomenclature. This classification system analytes. Also, misleading information about the num- would require general use in the newborn screening and ber of disorders covered by a test panel occurs when the subspecialty communities to become a consensus prod- number of disorders is inflated by counting disorder uct. Standardization of screening panels, including no- variants, while still failing to test for all disorders in the menclature, screening methods, and case definitions, ACMG recommended panel.7 The difference arises from would improve the quality of reported data. Good data a lack of uniformity in naming and counting disorders. quality is necessary for learning more about the natural history of the disorders, validating the utility of the screen- ACMG Report ing strategy, encouraging screening uniformity, and pro- The ACMG report1 summarized an extensive effort by a viding for more-uniform program quality assurance. We group of experts with diverse expertise within the new- also identify and comment on concerns related to the fact born screening system to determine a process for select- that some disorders listed in the ACMG report have not yet ing a uniform panel of newborn screening disorders. been identified through newborn screening, although the This expert group recognized that quantification and analytical procedure has been used to detect the disorder categorization of newborn screening disorders are im- among older patients in diagnostic laboratory settings. perfect and inconsistent and, until they are standardized, there will continue to be confusion about the extent of METHODS screening in individual programs and throughout the Background nation. The group recommended a common nomencla- Newborn screening laboratory testing procedures do not ture for the objective and scientifically valid screening identify disorders specifically; rather, they identify bio- test panel described. chemical markers (analytes) that are related to the dis- The ACMG expert group reviewed and modified tra- orders in question. In some cases, a second analytical ditional selection criteria for screening disorders,8 which process performed with the same sample detects a dif- originated in the 1960s and were established on the basis SUPPLEMENT S309 Downloaded from www.aappublications.org/news by guest on September 30, 2021 TABLE 1 Nomenclature for Conditions Included in the ACMG Recommended Uniform Panel for Newborn Screening Programs Condition/Disorder ACMG Code Primary Preferred Screening Analyte/Biomarker Strategy Endocrine disorders Thyroid disorders Primary congenital hypothyroidism CH T4 and TSH T4 and TSH immunoassay Disorders of adrenal steroidogenesis Congenital adrenal hyperplasia (MIM 201910) (steroid 21-hydroxylase CAH 17-OHP 17-OHP immunoassay deficiency ͓EC 1.14.99.10͔), salt-wasting, simple virilizing, or nonclassic Metabolic disorders Organic acid disorders Acylcarnitines by MS/MS Propionic acidemia (MIM 606054) (propionyl-CoA carboxylase deficiency PROPa C3