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.Incidence
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): Newborn Screening Services (see NW providers [1]).
- For evaluation and ongoing collaborative management, consult the following service(s): Pediatric Metabolics (see NW providers [0]).
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 NW providers [0]). 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)
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.
Genetics in Primary Care Institute (AAP)
Contains health supervision guidelines and other useful resources for the care of children with genetic disorders; American
Academy of Pediatrics.
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 Nationwide (NW)
| Service Categories | # of providers* in: | NW | Partner states (6) (show) | | ID | MT | NM | NV | RI | UT | |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Newborn Screening Services | 1 | 22 | 4 | 2 | 2 | 1 | 3 | ||||
| Nutrition Assessment Services | 1 | 1 | 83 | 5 | 2 | 8 | |||||
| Pediatric Genetics | 1 | 3 | 7 | 4 | 4 | 4 | 6 | ||||
| Pediatric Metabolics | 1 | 1 | 1 | 2 | 2 | ||||||
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
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.