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): Pediatric Metabolics (see NM providers [0]). 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)
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.

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.

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; Department of Education, Office of Special Education.

Services for Patients & Families in New Mexico (NM)

Genetics clinic services throughout the US can be found through the Genetics Clinic Services Search Engine (ACMG).

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

Initial publication: August 2016
Current Authors and Reviewers:
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.