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 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)
 
Decreased Citrulline
TIME CRITICAL*
Citrulline PDF
(2022)
PDF
(2022)
 
Guanidinoacetate Methyltransferase (GAMT) Deficiency Guanidinoacetate PDF
(2022)
PDF
(2022)
 ACMG Genetics AcademyVideo Only (2023)
Homocystinuria; Hypermethioninemia; GNMT; Adenosylhomocysteine hydrolase deficiency Methionine PDF
(2022)
PDF
(2022)
 
MSUD; Hydroxyprolinuria
TIME CRITICAL*
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)
TIME CRITICAL*
Elevated 17-OHP PDF
(2012)
PDF
(2012)
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)
 
Glutaric acidemia 2 Ethylmalonic encephalopathy
TIME CRITICAL*
C4;C5 PDF
(2022)
PDF
(2022)
 
LCHAD or TFP
TIME CRITICAL*
C16-OH +/- and C18:1-OH PDF
(2022)
PDF
(2022)
 
MCAD
TIME CRITICAL*
C8;C6,C10 PDF 
(2022)
PDF
(2022)
 ACMG Genetics Academy; Video Only (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)
 
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
(2022)
PDF
(2022)
 
Classical Galactosemia
TIME CRITICAL*
Absent/Reduced GALT PDF
(2022)
PDF
(2022)
 ACMG Genetics Academy; Video Only (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
(2022)
PDF
(2022)
 
Critical Congenital Heart Disease (CCHD)
TIME CRITICAL* 
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
(2023)
 PDF
(2023)
 ACMG Genetics Academy; Video Only (2022)
Hemoglobin Disorders
Condition Analyte ACT Sheet Algorithm
Sickle cell anemia (HbSS or HbSߺ Thalassemia) Hemoglobin FS PDF
(2023)
PDF 
(2023)
Hemoglobin SC disease (HbSC) Hemoglobin FSC PDF
(2023)
PDF
(2023)
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)
Alpha (α) Thalassemia  Hemoglobin FA + Unquantified Barts Hb   PDF
(2023)
PDF
(2023)
 Alpha (α) Thalassemia: Silent Carrier and Alpha Thalassemia Trait Hemoglobin FA + Low/Moderate Barts Hb PDF
(2023)
PDF
(2023)
 Alpha (α) Thalassemia: Hb H Disease Hemoglobin FA + High Barts Hb PDF
(2023)
PDF
(2023)
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)
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 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 (2023)
Krabbe Disease (Late -Onset Form) PDF
(2022)
PDF
(2022)
 ACMG Genetics AcademyVideo Only (2023)
Mucopolysaccharidosis Type 1 (MPS I) PDF
(2023)
PDF
(2023)
 ACMG Genetics AcademyVideo Only (2022)
Mucopolysaccharidosis Type II
PDF
(2022)
PDF
(2022)
 ACMG Genetics AcademyVideo Only (2023)
Acid Sphingomyelinase Deficiency (ASMD) (Formerly Niemann-Pick Disease) PDF
(2022)
PDF
(2022)
 
Pompe
TIME CRITICAL*
PDF
(2022)
PDF
(2022)
 ACMG Genetics AcademyVideo Only (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 (2021)
Organic Acidemias
Condition Analyte ACT Sheet Algorithm
Beta-ketothiolase deficiency; Biotinidase deficiency; Holocarboxylase deficiency; HMG-CoA lyase deficiency; 2M3HBA; 3MGA;3MCC
TIME CRITICAL*
C5-OH PDF
(2022)
PDF
(2022)
Glutaric acidemia 1
TIME CRITICAL*
C5-DC PDF
(2022)
PDF
(2022)
Isovaleric acidemia; Short/branched chain acyl-CoA dehydrogenase deficiency
TIME CRITICAL*
C5 PDF
(2022)
PDF
(2022)
Malonic acidemia
TIME CRITICAL*
C3-DC PDF 
(2022)
PDF 
(2022)
Methylmalonic acidemias; Propionic acidemia
TIME CRITICAL*
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)
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)
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)
*"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. Adapted from the Society of Inherited Metabolic Disorders.

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
Please see the NCC website for up-to-date author list.