Guanidinoacetate methyltransferase (GAMT) deficiency

Other Names

Cerebral creatine deficiency syndrome 2 (CCDS2)

Creatine deficiency syndrome due to GAMT deficiency

Diagnosis Coding

270.8, other specified disorders of amino-acid metabolism


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 Medical Genetics , (801-213-3599); See also Services below. 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 that provides technical information on this genetic disorder; Online Mendelian Inheritance in Man site, hosted by Johns Hopkins University.

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

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.

Genetics in Primary Care Institute (AAP)
The goal of this site is to increase collaboration in the care of children with known or suspected genetic disorders. Includes health supervision guidelines and other useful resources; a collaboration among the Health Resources & Services Administration, the Maternal and Child Health Bureau, and the American Academy of Pediatrics.

Utah Newborn Screening Program (UDOH)
Provides information about the program, related legislation, training for practices, and newborn conditions; Utah Department of Health.

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.

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; newsletters; factsheets; data reports; and publications; National Newborn Screening and Global Resource Center.

Utah Parent Center
A non-profit organization that provides training, information, referral, and assistance to parents of children and youth with all disabilities including physical, mental, hearing, vision, learning, behavioral, and emotional. Staff consists primarily of parents of children and youth with disabilities.

Center for Parent Information and Resources (DOE)
A large resource library related to children with disabilities. Parent Centers in every state provide training to parents of children with disabilities. Lists local conferences, support groups, advocacy tips, and suggestions for finding schools and other local services; Department of Education, Office of Special Education.


Genetics Clinic Directory (GeneTests)
Genetics-related clinical services throughout the world; U.S. National Library of Medicine.

Newborn Screening Programs

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


See all Nutrition/Dietary services providers (53) in our database.

Pediatric Genetics

See all Pediatric Genetics services providers (5) in our database.

Pediatric Metabolic Genetics

See all Pediatric Metabolic Genetics services providers (2) 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


Author: Kimberly Hart, MS, LCGC - 8/2016
Reviewing Author: Nicola Longo, MD, PhD - 8/2016
Content Last Updated: 8/2016

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.