The ACMG ACT Sheets and their accompanying algorithms are a great resources for health care providers looking for information on genetic conditions (identified through newborn screening and beyond) to help inform clinical decision making. Developed by the American College of Medical Genetics and Genomics and the National Coordinating Center for the Regional Genetics Networks (NCC), ACMG ACT Sheets are available on the ACMG websites. Given the rarity of many genetic conditions—ACT Sheets and algorithms are excellent refreshers on the conditions, diagnoses, and next steps for patients. 

For each marker(s), there is 1) an ACTion (ACT) sheet that describes the short term actions a health professional should follow in communicating with the family and determining the appropriate steps in the follow-up of the infant that has screened positive, and 2) an algorithm that presents an overview of the basic steps involved in determining the final diagnosis in the infant.

The first page of the ACT sheets includes information developed by the ACT Sheet Workgroup. Each ACT Sheet also include links to informational resources to allow the health professional to obtain additional information, if needed. The second page of the ACT sheet includes links to web sites that allow one to identify sub-specialists for consultation and referral for the condition(s) described in the ACT Sheet.

Would you like to search for a specific ACMG ACT Sheet or Algorithm? Or provide feedback on a particular ACMG ACT Sheet or Algorithm? Visit the NCC website to search or provide feedback!

Newborn Screening ACT Sheets and Algorithms
Amino Acidemias
Condition Analyte ACT Sheet Algorithm
Argininemia Arginine PDF
(2022)
PDF
(2022)
Argininosuccinic aciduria ; Citrullinemia I; Citrullinemia II; Pyruvate carboxylase deficiency Citrulline PDF 
(2022)
PDF
(2022)
Decreased Citrulline Citrulline PDF
(2022)
PDF
(2022)
Guanidinoacetate Methyltransferase (GAMT) Deficiency Guanidinoacetate PDF
(2022)
PDF
(2022)
Homocystinuria; Hypermethioninemia; GNMT; Adenosylhomocysteine hydrolase deficiency Methionine PDF
(2022)
PDF
(2022)
MSUD; Hydroxyprolinuria Leucine PDF
(2022)
PDF
(2022)
Phenylketonuria (PKU); Biopterin cofactor biosynthesis defect; Biopterin cofactor regeneration defect Phenylalanine PDF 
(2022)
PDF
(2022)
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
(2012)
PDF
(2012)
Secondary congenital hypothyroidism Low T4 +/- Elevated TSH PDF
(2012)
PDF
(2012)
Thyroxine binding globulin (TBG) deficiency Low T4 +/-Elevated TSH PDF
(2012)
PDF
(2012)
Congenital adrenal hyperplasia (CAH)(21-hydroxylase deficiency) Elevated 17-OHP PDF
(2012)
PDF
(2012)
Fatty Acid Oxidation Disorders
Condition Analyte ACT Sheet Algorithm
Carnitine uptake defect C0 PDF
(2022)
PDF
(2022)
CPT 1 deficiency C0; C0/C16+C18 PDF
(2022)
PDF
(2022)
CPT 2 or CACT C16 and/or C18:1 PDF
(2022)
PDF
(2022)
Glutaric acidemia 2 Ethylmalonic encephalopathy C4;C5 PDF
(2022)
PDF
(2022)
LCHAD or TFP C16-OH +/- and C18:1-OH PDF
(2012)
PDF
(2012)
MCAD C8;C6,C10 PDF 
(2022)
PDF
(2022)
Short Chain Hydroxyacyl-CoA Dehydrogenase (SCHAD) Deficiency
C4-OH PDF
(2022)
PDF
(2022)
Short-chain acyl-CoA deficiency (SCAD) Ethylmalonic encephalopathy Isobutyryl-CoA dehydrogenase deficiency C4 PDF
(2022)
PDF
(2022)
VLCAD C14:1 +/- PDF
(2012)
PDF
(2012)
Galactosemias
Condition Analyte ACT Sheet Algorithm
Primary or Secondary Hypergalactosemia Increase Total Galactose with normal GALT PDF
(2022)
PDF
(2022)
Classical Galactosemia Absent/Reduced GALT PDF
(2022)
PDF
(2022)
Genetic Disorders
Condition Analyte ACT Sheet Algorithm
Biotinidase deficiency Biotinidase PDF
(2022)
PDF
(2022)
Critical Congenital Heart Disease (CCHD)  PDF
(2013)
Cystic Fibrosis Immunoreactive trypsinogen (IRT) + IRT or DNA PDF
(2012)
PDF
(2006)
Hearing Loss PDF
(2012)
PDF 
(2009)
 X-Linked Adrenoleukodystrophy (X-ALD)  Elevated lysophosphatidylcholines PDF
(2020)
 In Development
Hemoglobin Disorders
Condition Analyte ACT Sheet Algorithm
Sickle cell anemia (HbSS or HbSߺ Thalassemia) Hemoglobin FS PDF
(2012)
PDF 
(2009)
Hemoglobin SC disease (HbSC) Hemoglobin FSC PDF
(2012)
PDF
(2009)
Hemoglobin S/beta Thalassemia (HbSß+) Hemoglobin FSA PDF
(2012)
PDF
(2009)
Sickle cell carrier (trait) (HbAS) Hemoglobin FAS PDF 
(2012)
PDF
(2009)
Hemoglobin V (variant) Hemoglobin FAV PDF
(2012)
PDF 
(2009)
Hemoglobin FE or Hemoglobin E/Beta Zero Thalassemia (Hb EE or Hb E/ߺ Disease) Hemoglobin FE PDF 
(2012)
PDF
(2009) 
Beta Thalassemia Major Hemoglobin F PDF
(2010)
PDF 
(2009)
Alpha Thalassemia (phenotype varies with % Barts Hb) Hemoglobin FA +Barts Hb PDF
(2012)
PDF 
(2009)
Hemoglobin CC Disease or Hemoglobin C/Beta Zero Thalassemia (HbC/ߺ Disease) Hemoglobin FC PDF
(2012)
PDF 
(2009)
Hemoglobin C/Beta Plus Thalassemia (HbC/ß+ Disease) Hemoglobin FCA PDF
(2012)
PDF 
(2009)
Hemoglobin E/Beta Plus Thalassemia (HbE/B+ Disease) Hemoglobin FAE PDF
(2012)
PDF 
(2009)
Immunodeficiency Disorders
Condition ACT Sheet Algorithm
Severe Combined Immunodeficiency (SCID) and Conditions Associated with T Cell Lymphoneia  PDF
(2012)
In Development
Lysosomal Storage Diseases
Condition ACT Sheet Algorithm
Fabry Disease PDF
(2022)
PDF
(2022)
Gaucher Disease PDF
(2022)
PDF
(2022)
Krabbe Disease (Infantile Form) PDF
(2022)
PDF
(2022)
Krabbe Disease (Late -Onsent Form) PDF
(2022)
PDF
(2022)
Mucopolysaccharidosis Type 1 (MPS I) PDF
(2020)
In Development
Mucopolysaccharidosis Type II
PDF
(2022)
PDF
(2022)
Acid Sphingomyelinase Deficiency (ASMD) (Formerly Niemann-Pick Disease) PDF
(2022)
PDF
(2022)
Pompe PDF
(2022)
PDF
(2022)
Musculoskeletal Disease
Condition Analyte ACT Sheet Algorithm
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) Exon 7 Deletion (Pathogenic Variant) in SMN1 gene  PDF
(2020)
 
Organic Acidemias
Condition Analyte ACT Sheet Algorithm
Beta-ketothiolase deficiency; Biotinidase deficiency; Holocarboxylase deficiency; HMG-CoA lyase deficiency; 2M3HBA; 3MGA;3MCC C5-OH PDF
(2022)
PDF
(2022)
Glutaric acidemia 1 C5-DC PDF
(2022)
PDF
(2022)
Isovaleric acidemia; Short/branched chain acyl-CoA dehydrogenase deficiency C5 PDF
(2022)
PDF
(2022)
Malonic acidemia C3-DC PDF 
(2022)
PDF 
(2022)
Methylmalonic acidemias; Propionic acidemia C3 PDF  
(2022)
PDF
(2022)
Carrier ACT Sheets and Algorithms

Condition Analyte ACT Sheet
Cystic Fibrosis CF Mutations except R117H PDF
(2012)
Cystic Fibrosis CF R117H PDF 
(2012)
Cystic Fibrosis No Mutations Detected by Carrier Screening PDF 
(2012)
Ashkenazi Jewish Genetic Disorders - PDF 
(2011)
Sickle Cell Carrier/Trait - PDF 
(2012)
Spinal Muscular Atrophy - PDF
(2012)
Diagnostic Test ACT Sheets

Condition  ACT Sheet
Muscular Dystrophy  PDF 
(2012)
Fragile X Syndrome  PDF 
(2012)
Family History ACT Sheets

Condition  ACT Sheet
Colon Cancer  PDF 
(2012)
Noninvasive Prenatal 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)
Transition ACT Sheets
Endocrine Disorders
Condition ACT Sheet
Congenital hypothyroidism PDF 
(2012)
Congenital Adrenal Hyperplasia (CAH) PDF  
(2012)
Hemoglobin Disorders
Condition ACT Sheet
Sickle Cell Disease PDF
(2012)
Urea Cycle Disorders
Condition ACT Sheet
Arginase Deficiency PDF
(2012)
Argininosuccinic Acidemia PDF
(2012)
Citrullinemia I PDF
(2012)
Citrullinemia II PDF
(2012)
CPS I Deficiency PDF
(2012)
NAGS Deficiency PDF 
(2012)
OTC Deficiency PDF
(2012)
Amino Acidemias
Condition ACT Sheet
Homocystinuria PDF
(2012)
Phenylketonuria PDF
(2012)
Galactosemias
Condition ACT Sheet
GALT Deficiency, Classical Galactosemia PDF
(2012)

Funding Disclaimer

The ACMG ACT Sheets are supported by the National Coordinating Center for the Regional Genetics Networks (NCC). NCC is supported by  the Health Resources and Services Administration (HRSA) of the U.S. Department of Health and Human Services (HHS) under Cooperative Agreement #UH9MC30770 from 6/2020-5/2024 for $800,000 per award year.

This information or content and conclusions are those of the author and should not be construed as the official position or policy of, nor should any endorsements be inferred by HRSA, HHS or the U.S. Government.

*Spanish Versions of the ACMG ACT Sheets- These resources are supported by the Health Resources and Services Administration (HRSA) of the U.S. Department of Health and Human Services (HHS) as part of an award totaling $2,400,000 with 0 percent financed with non-governmental sources. The contents are those of the author(s) and do not necessarily represent the official views of, nor an endorsement, by HRSA, HHS, or the U.S. Government. For more information, please visit HRSA.gov.

Disclaimer: The ACT sheets and algorithms are designed primarily as educational resources for physicians to help them provide quality medical services, and adherence to them does not necessarily ensure a successful medical outcome. The ACT sheets and algorithms 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 healthcare provider should apply his or her own professional judgment to the specific clinical circumstances presented by the individual patient or specimen. It may be prudent, however, to document in the patient’s record the rationale for any significant deviation from these ACT sheets and algorithms.

The Site contains links to third party websites. These links are provided solely as a convenience to users and not as a guarantee, warrantee, or recommendation by ACMG of the content on such third-party websites or as an indication of any affiliation, sponsorship or endorsement of such third party websites. ACMG is not responsible for the content of linked third-party sites and does not make any representations regarding the privacy practices of, or the content or accuracy of materials on, such third-party websites. If you decide to access linked third-party websites, you do so at your own risk. Your use of third-party websites is subject to the terms of use for such sites.
Authors


 
ACMG Newborn Screening Work Group Harvey L. Levy, MD (Co-Chair) Children’s Hospital Boston Michael S. Watson, PhD, FACMG (Project Director) American College of Medical Genetics and Genomics
Endocrinopathies Stephen LaFranchi, MD Oregon Health and Sciences University

Phyllis Speiser, MD Schneider Children’s Hospital, New York

Kelly Leight, JD CARES Foundation, Inc.
Hemoglobinopathies James R. Eckman, MD Emory University School of Medicine
Peter A. Lane, MD Emory University School of Medicine
Carolyn Hoppe, MD Children’s Hospital Oakland
Genetic Conditions Garry Cutting, MD Johns Hopkins University School of Medicine
Cynthia C. Morton, PhD Brigham and Women’s Hospital Boston
Richard Smith, MD University of Iowa School of Medicine
Metabolic Disorders Gerard Berry, MD Jefferson Medical College Stephen Goodman, MD University of Colorado Health Science Center
Deborah Marsden, MD Children’s Hospital Boston
Dietrich Matern, MD, PhD (Co-Chair) Mayo Clinic College of Medicine 
William Nyhan, MD University of California, San Diego
Primary Care Providers Danielle Laraque, MD, FAAP Mount Sinai School of Medicine
Robert Ostrander, MD, FAAP Valley View Family Practice
Barbara Yawn, MD, FAAFP Olmstead Medical Center
Newborn Screening Programs Julie Miller, MS Nebraska Department of Health and Human Services
Kenneth Pass, PhD New York State Dept. of Health
Bradford Therrell, PhD National Newborn Screening and Genetics Resource Center
MCHB/HRSA Marie Y. Mann, MD, MPH Genetic Services Branch Michele Lloyd-Puryear, MD, PhD Genetic Services Branch