Guanidinoacetate Methyltransferase (GAMT) Deficiency

Other Names

Cerebral creatine deficiency syndrome 2 (CCDS2)

Creatine deficiency syndrome due to GAMT deficiency

Diagnosis Coding

E72.8, other specified disorders of amino-acid metabolism

Disorder Category

An amino acidemia



Elevated guanidinoacetate

Tested By

Tandem mass spectrometry (MS/MS); sensitivity=100%; specificity=100% [Comeaux: 2013]


Guanidinoacetate methyltransferase (GAMT) deficiency is an inborn error of creatine synthesis resulting in deficiency of creatine and an accumulation of guanidinoacetate in tissues and body fluids, including the brain. The clinical phenotype includes developmental delays, speech delay, hypotonia, seizures, extrapyramidal movement, and autism-like behavior.


The prevalence of GAMT is unknown but estimated to be 1:114,000 in Utah. [Mercimek-Mahmutoglu: 2015]


Autosomal recessive

Prenatal Testing

DNA testing is by amniocentesis or chorionic villus sampling (CVS) if both disease causing mutations of an affected family member have been identified.

Clinical Characteristics

With early diagnosis and ongoing treatment, most affected children will have normal development. Without treatment, symptoms may begin between birth and 5 years of age and include global developmental delays, hypotonia, intellectual disability, impairment of expressive speech, autistic features, and varying neurological manifestations, including epilepsy and movement disorders.

Follow-up Testing after Positive Screen

Follow-up involves quantitative plasma and urine guanidinoacetate and creatine analysis.

Primary Care Management

Upon Notification of the + Screen

If the Diagnosis is Confirmed

  • Educate the family regarding signs, symptoms, and the need for specialized care.
  • Treatment should be continued for life and includes creatine (300-800 mg/kg/day), ornithine (300-800 mg/kg/day), and benzoate (100 mg/kg/day).
  • A low-protein diet may be indicated.
  • For those identified after irreversible consequences, the therapy above is still effective and should be started. Developmental and educational interventions are indicated.

Specialty Care Collaboration

If the child is affected, initiate a consultation and ongoing collaboration with the following service(s): see all Pediatric Metabolic Genetics services providers (1) in our database. A dietician may work with the family to devise an optimal approach to dietary management. Consider genetic counseling for the family.


Information & Support

For Professionals

Creatine Deficiency Syndromes (GeneReviews)
Excellent and extensive review by Saadet Mercimek-Mahmutoglu and Gajja S Salomons that includes causes, evaluation strategy, genetic counseling, management, resources, and references for CCDS2, GAMT, AGAT, and CRTR; U.S. National Library of Medicine.

Cerebral Creatine Deficiency Syndrome-2 (OMIM)
Extensive review of literature providing technical information for providers on genetic disorders; Online Mendelian Inheritance in Man site, hosted by Johns Hopkins University.

National Newborn Screening & Global Resource Center (NNSGRC)
Fact sheets, data reports, publications, and information for clinicians about genetic screening that includes links to state genetic contacts.

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.

For Parents and Patients

Guanidinoacetate Methyltransferase Deficiency (Genetics Home Reference)
Excellent, detailed review of the condition for patients and families; U.S. National Library of Medicine.

Baby's First Test (Genetic Alliance)
A clearinghouse for newborn screening information. Provides resources about screening at the local, state, and national levels and ways for people to 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.

Newborn Screening Information for Families (NNSGRC)
Information for families about genetic screening. Links to support groups, advocacy groups, and state genetic contacts; National Newborn Screening and Global Resource Center.

Center for Parent Information and Resources (CPIR)
Maintains a large resource library with information related to children with disabilities. Parent Information Centers in every state provide training to parents of children with disabilities and provide information about local conferences, support groups, and finding schools and other local services. Department of Education, Office of Special Education.

Services in Montana

Select services for a different state: ID, NM, NV, RI, UT
Genetics clinic services throughout the US can be found through the Genetics Clinic Services Search Engine (ACMG).

Newborn Screening Programs

See all Newborn Screening Programs services providers (3) in our database.

Nutrition Assessment Services

See all Nutrition Assessment Services services providers (2) in our database.

Pediatric Genetics

See all Pediatric Genetics services providers (6) in our database.

Pediatric Metabolic Genetics

See all Pediatric Metabolic Genetics services providers (1) in our database.

For other services related to this condition, browse our Services categories or search our database.

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

Initial Publication: July 2016; Last Update: August 2016
Current Authors and Reviewers (click on name for bio):
Author: Kimberly Hart, MS, LCGC
Reviewer: Nicola Longo, MD, Ph.D.

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

Mercimek-Mahmutoglu S, Salomons GS.
Creatine Deficiency Syndromes.
GeneReviews; (2015) Available from: Accessed on 8/12/16.