Guanidinoacetate Methyltransferase (GAMT) Deficiency
Other Names
Cerebral creatine deficiency syndrome 2 (CCDS2)
Creatine deficiency syndrome due to GAMT deficiency
Screening
Tested By
Tandem mass spectrometry (MS/MS); sensitivity=100%; specificity=100% [Comeaux: 2013]Overview
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.Prevalence
The prevalence of GAMT is unknown but estimated to be 1:114,000 in Utah. [Mercimek-Mahmutoglu: 2015]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
- Contact the family and evaluate the infant for hypotonia, seizures, and developmental delays.
- To confirm the diagnosis, work with the following service(s): see all Newborn Screening Programs services providers (2) in our database.
- For evaluation and ongoing collaborative management, consult the following service(s): Pediatric Medical Genetics, (801-213-3599); See also Services below.
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.Resources
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.
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. It includes
health supervision guidelines and other useful resources; represents 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; 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.
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 and provide information about local conferences, support groups, and finding schools and other
local services; Department of Education, Office of Special Education.
Services
Genetics-related clinical services throughout the world; U.S. National Library of Medicine.
Newborn Screening Programs
See all Newborn Screening Programs services providers (2) 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
Authors
| 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)
http://www.ncbi.nlm.nih.gov/books/NBK3794/. Available from: http://www.ncbi.nlm.nih.gov/books/NBK3794/. Accessed on 8/12/16.