The ACMG ACTion (ACT) Sheets and their accompanying algorithms are an essential resource for health care providers to help inform clinical decision making when an initial screen positive newborn screen is received. Previously under the auspices of the HRSA-funded National Coordinating Center for the Regional Genetics Networks and continuously developed by the American College of Medical Genetics and Genomics with national topic experts, they provide concise current information about the disorder as well as initial guidance to help manage a screen positive result. This includes prompt actions a healthcare professional can follow when communicating with the family, determining the appropriate next steps to evaluate the newborn and reach a diagnosis, and provide resource links for further information. The accompanying algorithm presents an overview of the basic laboratory steps involved in determining the final diagnosis in the infant.
ACMG ACT Sheets are freely available on the ACMG website regardless of membership status.
Newborn Screening ACT Sheets and Algorithms
Amino Acidemias
Analyte: Citrulline
Analyte: Citrulline
Analyte: Guanidinoacetate
Analyte: Methionine
Analyte: Leucine
Analyte: Phenylalanine
Analyte: Tyrosine SUAC Normal
Analyte: Tyrosine Normal/Elevated and SUAC Elevated
Critical Congenital Heart Disease
Analyte: Blood oxygen saturation levels
Endocrine Disorders
Analyte: Elevated TSH
Analyte: Low T4 +/- Abnormal TSH
Analyte: Elevated 17-OHP
Fatty Acid Oxidation Disorders
Analyte: C0; C0/C16+C18
Analyte: C16 and/or C18:1
Analyte: C4; C5
Analyte: C16-OH +/- and C18:1-OH
Analyte: C4-OH
Analyte: C4
Galactosemias
Analyte: Increased Total Galactose with normal GALT
Analyte: Absent/Reduced GALT
Genetic Disorders
Analyte: Elevated Immunoreactive trypsinogen (IRT) + 0 Variants
Analyte: Elevated Immunoreactive trypsinogen (IRT) + 1 Variant
Analyte: Elevated Immunoreactive trypsinogen (IRT) + 2 Variants
Analyte: Elevated lysophosphatidylcholines
Hemoglobin Disorders
Analyte: Hemoglobin FS
Analyte: Hemoglobin FSC
Analyte: Hemoglobin FSA
Analyte: Hemoglobin FAS
Analyte: Hemoglobin FE
Analyte: Hemoglobin F
Analyte: Hemoglobin FA + Unquantified Barts Hb
Analyte: Hemoglobin FA + Low/Moderate Barts Hb
Analyte: Hemoglobin FA + High Barts Hb
Analyte: Hemoglobin FC
Analyte: Hemoglobin FCA
Analyte: Hemoglobin FEA
Lysosomal Storage Diseases
Musculoskeletal Disease
Analyte: Elevated Creatine Kinase Muscle Isoform
Analyte: Exon 7 Deletion (Pathogenic Variant) in SMN1 gene
Organic Acidemias
Analyte: C5-OH
Analyte: C5
Analyte: C3
Prenatal Cell-Free DNA Screening ACT Sheets
Secondary Findings ACT Sheets
Biomarker: APC Pathogenic Variants
Biomarker: APOB, LDLR, PCSK9 Pathogenic Variants
Biomarker: BRCA1 and BRCA2 Pathogenic Variants
Biomarker: MLH1, MSH2, MSH6, PMS2, EPCAM Pathogenic Variants
Biomarker: RYR1 and CACNA1S Pathogenic Variants
*”Time Critical” is a condition in which acute symptoms or potentially irreversible damage could develop in the first week of life, and for which early recognition and treatment can reduce risk of morbidity and mortality.
Disclaimer: This ACT sheet and algorithm is designed primarily as an educational resource for medical geneticists and other clinicians to help them provide quality medical services. Adherence to this ACT sheet and algorithm is completely voluntary and does not necessarily assure a successful medical outcome. This ACT sheet and algorithm should not be considered inclusive of all proper procedures and tests or exclusive of other procedures and tests that are reasonably directed to obtaining the same results. In determining the propriety of any specific procedure or test, the clinician should apply their own professional judgment to the specific clinical circumstances presented by the individual patient or specimen. Clinicians are encouraged to document the reasons for the use of a particular procedure or test, whether or not it is in conformance with this ACT sheet and algorithm. Clinicians also are advised to take notice of the date this ACT sheet and algorithm was adopted, and to consider other medical and scientific information that becomes available after that date. It also would be prudent to consider whether intellectual property interests may restrict the performance of certain tests and other procedures. Where individual authors are listed, the views expressed may not reflect those of the authors’ employers or affiliated institutions.
Authors
ACMG ACT Sheet Advisory Committee (Current)
Dietrich Matern, MD, PhD, FACMG (Chair)
Biochemical Genetics Laboratory, Mayo Clinic, Rochester, MN
Tina Cowan, PhD, FACMG
Department of Pathology, Stanford University Medical Center, Stanford, CA
Amy Gaviglio, MS, CGC
Connetics Consulting, LLC, Minneapolis, MN
Andrea M. Matthews (Public Member)
Children’s Sickle Cell Foundation, Inc., Pittsburgh, PA
Robert Ostrander, MD, FAAFP
Rural Medical Scholars Program, Department of Family Medicine, SUNY Upstate Medical University, Syracuse, NY
Tracy Trotter, MD, FAAP, FACMG
John Muir Health, San Ramon, CA
Tim Wood, PhD, FACMG
Children’s Hospital of Colorado, University of Colorado Anschutz Medical Campus, Aurora, CO
Jing Xiao, PhD, FACMG
New York State Newborn Screening Program, Albany, NY
Nancy C. Rose, MD, FACMG (Medical Consultant)
University of Utah, Salt Lake City, UT
Sandor Roberts (ACMG Staff)
Metabolic ACT Sheet Document Review Work Group (2025-2026)
Katherine Anderson, MD, FACMG
Larner College of Medicine, University of Vermont, Burlington, VT
Troy Coody, PhD, FACMG
Cycle Pharmaceuticals, Salt Lake City, UT
Debra Freedenberg, MD, PhD, FACMG
Dietrich Matern, MD, PhD, FACMG
Biochemical Genetics Laboratory, Mayo Clinic, Rochester, MN
Wendy Smith, MD, FACMG
Division of Genetics, Maine Medical Center, Portland, ME
Janet Thomas, MD, FACMG
University of Colorado School of Medicine, Aurora, CO
Nancy C. Rose, MD, FACMG (Medical Consultant)
University of Utah, Salt Lake City, UT
Sandor Roberts (ACMG Staff)
Critical Congenital Heart Disease Work Group (2026)
Lisa Hom, RN, ESQ
Children’s National Heart & Lung Center, Children’s National Hospital, Washington, DC
Gerard Martin, MD, MACC, FAHA, FAAP
Children’s National Heart & Lung Center, Children’s National Hospital, Washington, DC
Erin Miller, MS
University of Cincinnati College of Medicine; Cincinnati Children’s Hospital Medical Center, Cincinnati, OH
Ana Morales, MS, CGC
Department of Genomic Health, Geisinger, Danville, PA
Matthew Oster, MD, MPH
Children’s Healthcare of Atlanta Cardiology, Emory University School of Medicine, Atlanta, GA
Bryanna Schwartz, MD, MPH
Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, Bethesda, MD; Children’s National Heart & Lung Center, Children’s National Hospital, Washington, DC
Nancy C. Rose, MD, FACMG (Medical Consultant)
University of Utah, Salt Lake City, UT
Sandor Roberts (ACMG Staff)
Metachromatic Leukodystrophy Work Group (2025, work completed)
Laura Adang, MD, PhD, MSTR
Division of Child Neurology, Children’s Hospital of Philadelphia, Philadelphia, PA
Joshua Bonkowsky, MD, PhD
Division of Pediatric Neurology, University of Utah, Salt Lake City, UT
Michele Caggana, ScD, FACMG
Retired, New York State Department of Health, Albany, NY
Natalia Gomez-Ospina, MD, PhD
Department of Pediatrics, Stanford University, Stanford, CA
Hannah Hart, LGC
Division of Pediatric Neurology, University of Utah, Salt Lake City, UT
Dietrich Matern, MD, PhD, FACMG
Biochemical Genetics Laboratory, Mayo Clinic, Rochester, MN
Paul Orchard, MD
Division of Blood & Marrow Transplantation & Cellular Therapy, University of Minnesota, Minneapolis, MN
Nancy C. Rose, MD, FACMG (Medical Consultant)
University of Utah, Salt Lake City, UT
Sandor Roberts (ACMG Staff)