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
Condition Analyte ACT Sheet Algorithm Knowledge Nuggets 
Short, animated videos that accompany specific ACMG ACT Sheets. Learn more here. 
Argininemia Arginine PDF
(2022)
PDF
(2022)
 
Argininosuccinic aciduria ; Citrullinemia I; Citrullinemia II; Pyruvate carboxylase deficiency
TIME CRITICAL*
Citrulline PDF 
(2022)
PDF
(2022)
ACMG Genetics AcademyVideo Only (Video Run Time- 8:29; Year Published 2023)
Decreased Citrulline
TIME CRITICAL*
Citrulline PDF
(2022)
PDF
(2022)
 
Guanidinoacetate Methyltransferase (GAMT) Deficiency Guanidinoacetate PDF
(2022)
PDF
(2022)
ACMG Genetics AcademyVideo Only (Video Run Time- 7:27; Year Published 2023)
Homocystinuria; Hypermethioninemia; GNMT; Adenosylhomocysteine hydrolase deficiency Methionine PDF
(2026)
PDF
(2026)

MSUD; Hydroxyprolinuria
TIME CRITICAL*
Leucine PDF
(2026)
PDF
(2026)
 
Phenylketonuria (PKU); Biopterin cofactor biosynthesis defect; Biopterin cofactor regeneration defect Phenylalanine PDF
(2022)
PDF
(2022)
 ACMG Genetics AcademyVideo Only (Video Run Time- 9:00; Year Published 2024)
Tyrosinemia I; Tyrosinemia II; Tyrosinemia III Tyrosine SUAC Normal PDF 
(2022)
PDF
(2022)
 
Tyrosinemia I; Tyrosinemia II; Tyrosinemia III Tyrosine Normal/Elevated and SUAC Elevated PDF 
(2022)
PDF
(2022)
 
Endocrine Disorders
Condition Analyte ACT Sheet Algorithm
Primary congenital hypothyroidism Elevated TSH PDF
(2024)
Low T4 and Elevated TSH- PDF
(2024)

Low T4 and Abnormal TSH- PDF
(2024)
Congenital central hypothyroidism
Low T4 +/- Abnormal TSH PDF
(2024)
PDF
(2024)
Congenital adrenal hyperplasia (CAH)(21-hydroxylase deficiency)
TIME CRITICAL*
Elevated 17-OHP PDF
(2024)
PDF
(2024)
Fatty Acid Oxidation Disorders
Condition Analyte ACT Sheet Algorithm Knowledge Nuggets 
Short, animated videos that accompany specific ACMG ACT Sheets. Learn more here 
Carnitine uptake defect C0 PDF
(2022)
PDF
(2022)
 
CPT 1 deficiency
TIME CRITICAL*
*C0; C0/C16+C18 PDF
(2022)
PDF
(2022)
 
CPT 2 or CACT
TIME CRITICAL*
C16 and/or C18:1 PDF
(2022)
PDF
(2022)
ACMG Genetics AcademyVideo Only (Video Run Time- 10:30; Year Published 2024)
Glutaric acidemia 2 Ethylmalonic encephalopathy
TIME CRITICAL*
C4;C5 PDF
(2022)
PDF
(2022)
ACMG Genetics AcademyVideo Only (Video Run Time- 9:48; Year Published 2024)
LCHAD or TFP
TIME CRITICAL*
C16-OH +/- and C18:1-OH PDF
(2022)
PDF
(2022)
ACMG Genetics AcademyVideo Only (Video Run Time- 9:35; Year Published 2024)
MCAD
TIME CRITICAL*
C8;C6,C10 PDF
(2026)
PDF
(2026)
ACMG Genetics Academy;Video Only(Video Run Time- 7:50; Year Published 2023)
Short Chain Hydroxyacyl-CoA Dehydrogenase (SCHAD) Deficiency
TIME CRITICAL*
C4-OH PDF
(2022)
PDF
(2022)
 
Short-chain acyl-CoA deficiency (SCAD) Ethylmalonic encephalopathy Isobutyryl-CoA dehydrogenase deficiency C4 PDF
(2022)
PDF
(2022)
 
VLCAD
TIME CRITICAL*
C14:1 +/- PDF
(2022)
PDF
(2022)
 ACMG Genetics AcademyVideo Only (Video Run Time- 9:28; Year Published 2024)
Galactosemias
Condition Analyte ACT Sheet Algorithm Knowledge Nuggets 
Short, animated videos that accompany specific ACMG ACT Sheets. Learn more here.  
Primary or Secondary Hypergalactosemia Increase Total Galactose with normal GALT PDF
(2026)
PDF
(2026)
ACMG Genetics Academy; Video Only (Video Run Time- 8:35; Year Published 2024)
Classical Galactosemia
TIME CRITICAL*
Absent/Reduced GALT PDF
(2026)
PDF
(2026)
ACMG Genetics Academy; Video Only (Video Run Time- 7:57; Year Published 2023)
Genetic Disorders
Condition Analyte ACT Sheet Algorithm Knowledge Nuggets 
Short, animated videos that accompany specific ACMG ACT Sheets. Learn more here
Biotinidase deficiency Biotinidase PDF
(2026)
PDF
(2026)
ACMG Genetics Academy;Video Only (Video Run Time- 7:48; Year Published 2023)
Cystic Fibrosis Elevated IRT + 0 Variants Elevated Immunoreactive trypsinogen (IRT) + 0 Variants PDF
(2024)
PDF
(2024)
 
Cystic Fibrosis Elevated IRT + 1 Variant Elevated Immunoreactive trypsinogen (IRT) + 1 Variant PDF
(2024)
PDF
(2024)
 
Cystic Fibrosis Elevated IRT + 2 Variants Elevated Immunoreactive trypsinogen (IRT) + 2 Variants PDF
(2024)
PDF
(2024)
 
Congenital Hearing Loss
PDF
(2024)
PDF
(2024)
 
 X-Linked Adrenoleukodystrophy (X-ALD)  Elevated lysophosphatidylcholines
PDF
(2023)
 PDF
(2023)
 ACMG Genetics Academy; Video Only (Video Run Time- 8:56; Year Published 2022)
Hemoglobin Disorders
Condition Analyte ACT Sheet Algorithm Knowledge Nuggets 
Short, animated videos that accompany specific ACMG ACT Sheets. Learn more here 
Sickle cell anemia (HbSS or HbSߺ Thalassemia) Hemoglobin FS PDF
(2023)
PDF 
(2023)
 Video Only (Video Run Time- 9:58; Year Published 2024)
Hemoglobin SC disease (HbSC) Hemoglobin FSC PDF
(2023)
PDF
(2023)
 Video Only (Video Run Time- 10:07; Year Published 2024)
Hemoglobin S/beta Thalassemia (HbSß+) Hemoglobin FSA PDF
(2023)
PDF
(2023)
 
Sickle cell carrier (trait) (HbAS) Hemoglobin FAS PDF 
(2023)
PDF
(2023)
 
Hemoglobin V (variant) Hemoglobin FAV PDF
(2023)
PDF 
(2023)
 
Hemoglobin FE or Hemoglobin E/Beta Zero Thalassemia (Hb EE or Hb E/ߺ Disease) Hemoglobin FE PDF 
(2023)
PDF
(2023) 
 
Beta Thalassemia Major and Intermedia Hemoglobin F PDF
(2023)
PDF
(2023)
 Video Only  (Video Run Time- 10:59; Year Published 2024)
Alpha (α) Thalassemia  Hemoglobin FA + Unquantified Barts Hb   PDF
(2023)
PDF
(2023)
 Video Only (Video Run Time- 10:21; Year Published 2024)
 Alpha (α) Thalassemia: Silent Carrier and Alpha Thalassemia Trait Hemoglobin FA + Low/Moderate Barts Hb PDF
(2023)
PDF
(2023)
 Video Only (Video Run Time- 10:21; Year Published 2024)
 Alpha (α) Thalassemia: Hb H Disease Hemoglobin FA + High Barts Hb PDF
(2023)
PDF
(2023)
 Video Only (Video Run Time- 10:21; Year Published 2024)
Hemoglobin CC Disease or Hemoglobin C/Beta Zero Thalassemia (HbC/ߺ Disease) Hemoglobin FC PDF
(2023)
PDF
(2023)
 
Hemoglobin C/Beta Plus Thalassemia (HbC/ß+ Disease) Hemoglobin FCA PDF
(2023)
PDF
(2023)
 
Hemoglobin E/Beta Plus Thalassemia (HbE/B+ Disease) Hemoglobin FEA PDF
(2023)
PDF
(2023)
 
Lysosomal Storage Diseases
Condition ACT Sheet Algorithm Knowledge Nuggets 
Short, animated videos that accompany specific ACMG ACT Sheets. Learn more here. 
Fabry Disease PDF
(2022)
PDF
(2022)
 
Gaucher Disease PDF
(2022)
PDF
(2022)
 
Krabbe Disease (Infantile Form)
TIME CRITICAL*
PDF
(2022)
PDF
(2022)
 ACMG Genetics AcademyVideo Only (Video Run Time- 8:34; Year Published 2023)
Krabbe Disease (Late -Onset Form) PDF
(2022)
PDF
(2022)
 ACMG Genetics AcademyVideo Only (Video Run Time- 8:34; Year Published 2023)
Metachromatic Leukodystrophy PDF
(2026)
PDF
(2026)
 
Mucopolysaccharidosis Type 1 (MPS I) PDF
(2023)
PDF
(2023)
 ACMG Genetics AcademyVideo Only (Video Run Time- 8:53; Year Published 2022)
Mucopolysaccharidosis Type II
PDF
(2022)
PDF
(2022)
 ACMG Genetics AcademyVideo Only (Video Run Time- 9:02; Year Published 2023)
Acid Sphingomyelinase Deficiency (ASMD) (Formerly Niemann-Pick Disease) PDF
(2022)
PDF
(2022)
 
Pompe
TIME CRITICAL*
PDF
(2022)
PDF
(2022)
ACMG Genetics AcademyVideo Only (Video Run Time- 8:42; Year Published 2023)
Musculoskeletal Disease
Condition Analyte ACT Sheet Algorithm  Knowledge Nuggets 
Short, animated videos that accompany specific ACMG ACT Sheets. Learn more here.
DMD Pathogenic Variant Pathogenic Variants in DMD gene PDF
(2019)
   
DMD Elevated Creatine Kinase Muscle Isoform Elevated Creatine Kinase Muscle Isoform PDF
(2019)
 PDF
(2022)
 
No Pathogenic Variant DMD Gene No Pathogenic Variant in DMD gene PDF
(2019)
   
Spinal Muscular Atrophy (SMA)
TIME CRITICAL*
Exon 7 Deletion (Pathogenic Variant) in SMN1 gene  PDF
(2020)
   ACMG Genetics AcademyVideo Only (Video Run Time- 7:23; Year Published 2021)
Organic Acidemias
Condition Analyte ACT Sheet Algorithm   Knowledge Nuggets 
Short, animated videos that accompany specific ACMG ACT Sheets. Learn more here.
Beta-ketothiolase deficiency; Biotinidase deficiency; Holocarboxylase deficiency; HMG-CoA lyase deficiency; 2M3HBA; 3MGA;3MCC
TIME CRITICAL*
C5-OH PDF
(2022)
PDF
(2022)
ACMG Genetics AcademyVideo Only (Video Run Time- 7:58; Year Published 2024)
Glutaric acidemia 1
TIME CRITICAL*
C5-DC PDF
(2022)
PDF
(2022)
 ACMG Genetics AcademyVideo Only (Video Run Time- 9:41; Year Published 2024)
Isovaleric acidemia; Short/branched chain acyl-CoA dehydrogenase deficiency
TIME CRITICAL*
C5 PDF
(2022)
PDF
(2022)
 ACMG Genetics AcademyVideo Only (Video Run Time- 9:19; Year Published 2024)
Malonic acidemia
TIME CRITICAL*
C3-DC PDF 
(2022)
PDF 
(2022)
 
Methylmalonic acidemias; Propionic acidemia
TIME CRITICAL*
C3 PDF  
(2022)
PDF
(2022)
ACMG Genetics AcademyVideo Only (Video Run Time- 9:29; Year Published 2024)
Prenatal Cell-Free DNA Screening ACT Sheets

Condition  ACT Sheet
45,X  PDF  
(2021)
Trisomy 13  English Version; Spanish Version(2020)
Trisomy 18  English Version; Spanish Version(2020)
Trisomy 21  English Version; Spanish Version(2020)
Secondary Findings ACT Sheets

Condition Biomarker ACT Sheet
Familial Adenomatous Polyposis APC Pathogenic Variants English Version (2019); Spanish Version(2020) 
Familial Hypercholesterolemia APOB, LDLR, PCSK9 Pathogenic Variants English Version (2019); Spanish Version(2020)
Hereditary Breast and Ovarian Cancer BRCA1 and BRCA2 Pathogenic Variants English Version (2019); Spanish Version(2020)
Lynch Syndrome MLH1, MSH2, MSH6, PMS2, EPCAM Pathogenic Variants  English Version (2019); Spanish Version(2020)
Malignant Hyperthermia RYR1 and CACNA1S Pathogenic Variants  English Version (2019); Spanish Version(2020)
*"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

Medical Consultant
Nancy C. Rose, MD, FACMG
University of Utah. Salt Lake City, UT

ACMG Staff
Sandor Roberts

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

Medical Consultant
Nancy C. Rose, MD, FACMG
University of Utah. Salt Lake City, UT

ACMG Staff
Sandor Roberts

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

Medical Consultant
Nancy C. Rose, MD, FACMG
University of Utah. Salt Lake City, UT

ACMG Staff
Sandor Roberts

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

Medical Consultant
Nancy C. Rose, MD, FACMG
University of Utah. Salt Lake City, UT

ACMG Staff
Sandor Roberts