Newborn Screening
Guanidinoacetate Methyltransferase (GAMT) Deficiency
Guidance for primary care clinicians receiving a positive newborn screen result
Description
Guanidinoacetate methyltransferase (GAMT) deficiency is an inborn error of creatine synthesis resulting in creatine deficiency and an accumulation of the toxic metabolite (GAA) guanidinoacetate in tissues and body fluids, including the brain. The clinical phenotype includes developmental delays, speech delay, hypotonia, seizures, extrapyramidal movements, ataxia, and autism-like behavior. With early diagnosis, treatments to reduce GAA levels can allow for normal growth and development before irreversible neurological damage occurs.
Clinical Characteristics
Incidence
Primary Care Management
Next Steps After a Positive Screen
- Contact the family and evaluate the infant for hypotonia, seizures, and developmental delays.
Confirming the Diagnosis
- To confirm the diagnosis of GAMT deficiency, work with Newborn Screening Services (see NW providers [1]).
- Follow-up involves quantitative plasma and
urine guanidinoacetate and creatine snd creatinine analysis.
- Molecular genetic testing may be necessary to confirm the diagnosis,
If the Diagnosis is Confirmed
- For evaluation and ongoing collaborative management, consult Medical Genetics (see NW providers [1]).
- Educate the family regarding signs, symptoms, and the need for specialized care.
- Treatment of GAMT deficiency aims at promoting growth and development and reducing GAA levels with ornithine, benzoate, and in some cases, a protein restriction, as well as supplementation of creatine under the guidance of a metabolic specialist
- Developmental and educational interventions are indicated. See Early Intervention for Children with Disabilities/Delays (see NW providers [3]).
Resources
Information & Support
After a Diagnosis or Problem is Identified
Families can face a big change when their baby tests positive for
a newborn condition. Find information about A New Diagnosis - You Are Not Alone;
Caring for Children with Special Health Care Needs; Assistance in Choosing
Providers; Partnering with Healthcare Providers; Top Ten Things to Do After a
Diagnosis.
For Professionals
Creatine Deficiency Disorders (GeneReviews)
Detailed information addressing clinical characteristics, diagnosis/testing, management, genetic counseling, and molecular
pathogenesis; from the University of Washington and the National Library of Medicine.
Cerebral Creatine Deficiency Syndrome-2 (OMIM)
Information about clinical features, diagnosis, management, and molecular and population genetics; Online Mendelian Inheritance
in Man, authored and edited at the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine
Guanidinoacetate Methyltransferase Deficiency (Orphanet)
An overview of genetics, diagnosis, and management of GAMT; Orphanet is a French-coordinated consortium involving over 40
countries to provide a portal for information about rare diseases and orphan drugs.
Communicating Newborn Screening Results to Families (ACHDNC)
One-page guide to help clinicians effectively communicate positive newborn screening results to parents; Advisory Committee
on Heritable Disorders in Newborns and Children.
For Parents and Patients
Guanidinoacetate Methyltransferase Deficiency (MedlinePlus)
Information for families that includes description, frequency, causes, inheritance, other names, and additional resources;
from the National Library of Medicine.
Association for Creatine Deficiencies
Established by parents of children diagnosed with a cerebral creatine deficiency syndrome to provide patient, family, and
public education, advocate for early intervention, and fund medical research for treatments and cures.
Baby's First Test (Genetic Alliance)
Clearinghouse for local, state, and national newborn screening education, programs, policies, and resources. Also, provides
many ways for people to connect and share their viewpoints and questions about newborn screening, supported by the U.S. Department
of Health and Human Services.
Disease InfoSearch for GAMT (Genetic Alliance)
Compilation of links to information, articles, research, and case studies for GAMT.
Center for Parent Information and Resources (DOE)
Parent Centers in every state provide training to parents of children with disabilities and provide information about special
education, transition to adulthood, health care, support groups, local conferences, and other federal, state, and local services.
See the "Find Your Parent Center Link" to find the parent center in your state.
Tools
ACT Sheet for Guanidinoacetate Methyltransferase Deficiency (ACMG)
Contains short-term recommendations for clinical follow-up of the newborn who has screened positive; American College of Medical
Genetics.
Confirmatory Algorithm for Elevated Guanidinoacetate (ACMG)
An algorithm of the basic steps involved in determining the final diagnosis of an infant with a positive newborn screen; American
College of Medical Genetics.
Services for Patients & Families Nationwide (NW)
| Service Categories | # of providers* in: | NW | Partner states (4) (show) | | NM | NV | RI | UT | |
|---|---|---|---|---|---|---|---|---|---|
| Biochemical Genetics (Metabolics) | 1 | 1 | 2 | 3 | 2 | ||||
| Dieticians and Nutritionists | 1 | 1 | 4 | 3 | 6 | ||||
| Early Intervention for Children with Disabilities/Delays | 3 | 34 | 31 | 13 | 51 | ||||
| Medical Genetics | 1 | 2 | 5 | 4 | 7 | ||||
| Newborn Screening Services | 1 | 3 | 2 | 2 | 3 | ||||
For services not listed above, browse our Services categories or search our database.
* number of provider listings may vary by how states categorize services, whether providers are listed by organization or individual, how services are organized in the state, and other factors; Nationwide (NW) providers are generally limited to web-based services, provider locator services, and organizations that serve children from across the nation.
Helpful Articles
PubMed search for GAMT deficiency and newborn screening.
Stockler-Ipsiroglu S, van Karnebeek C, Longo N, Korenke GC, Mercimek-Mahmutoglu S, Marquart I, Barshop B, Grolik C, Schlune
A, Angle B, Araújo HC, Coskun T, Diogo L, Geraghty M, Haliloglu G, Konstantopoulou V, Leuzzi V, Levtova A, Mackenzie J, Maranda
B, Mhanni AA, Mitchell G, Morris A, Newlove T, Renaud D, Scaglia F, Valayannopoulos V, van Spronsen FJ, Verbruggen KT, Yuskiv
N, Nyhan W, Schulze A.
Guanidinoacetate methyltransferase (GAMT) deficiency: outcomes in 48 individuals and recommendations for diagnosis, treatment
and monitoring.
Mol Genet Metab.
2014;111(1):16-25.
PubMed abstract
Viau KS, Ernst SL, Pasquali M, Botto LD, Hedlund G, Longo N.
Evidence-Based Treatment of Guanidinoacetate Methyltransferase (GAMT) Deficiency.
Mol Genet Metab.
2013;110(3):255-62.
PubMed abstract
Authors & Reviewers
| Author: | Brian J. Shayota, MD, MPH |
| Reviewer: | Nancy C. Rose, MD |
| 2023: update: Brian J. Shayota, MD, MPHA |
| 2016: first version: Kimberly Hart, MS, LCGCA; Nicola Longo, MD, Ph.D.R |
Page Bibliography
Comeaux MS, Wang J, Wang G, Kleppe S, Zhang VW, Schmitt ES, Craigen WJ, Renaud D, Sun Q, Wong LJ.
Biochemical, molecular, and clinical diagnoses of patients with cerebral creatine deficiency syndromes.
Mol Genet Metab.
2013;109(3):260-8.
PubMed abstract
Hart K, Rohrwasser A, Wallis H, Golsan H, Shao J, Anderson T, Wang X, Szabo-Fresnais N, Morrissey M, Kay DM, Wojcik M, Galvin-Parton
PA, Longo N, Caggana M, Pasquali M.
Prospective identification by neonatal screening of patients with guanidinoacetate methyltransferase deficiency.
Mol Genet Metab.
2021;134(1-2):60-64.
PubMed abstract
Stockler-Ipsiroglu S, van Karnebeek C, Longo N, Korenke GC, Mercimek-Mahmutoglu S, Marquart I, Barshop B, Grolik C, Schlune
A, Angle B, Araújo HC, Coskun T, Diogo L, Geraghty M, Haliloglu G, Konstantopoulou V, Leuzzi V, Levtova A, Mackenzie J, Maranda
B, Mhanni AA, Mitchell G, Morris A, Newlove T, Renaud D, Scaglia F, Valayannopoulos V, van Spronsen FJ, Verbruggen KT, Yuskiv
N, Nyhan W, Schulze A.
Guanidinoacetate methyltransferase (GAMT) deficiency: outcomes in 48 individuals and recommendations for diagnosis, treatment
and monitoring.
Mol Genet Metab.
2014;111(1):16-25.
PubMed abstract
Viau KS, Ernst SL, Pasquali M, Botto LD, Hedlund G, Longo N.
Evidence-Based Treatment of Guanidinoacetate Methyltransferase (GAMT) Deficiency.
Mol Genet Metab.
2013;110(3):255-62.
PubMed abstract