Guanidinoacetate methyltransferase deficiency
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
Age of Onset
Autosomal dominant ?A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease
Autosomal recessive ?Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype
X-linked dominant ?X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.
X-linked recessive ?Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder
Mitochondrial or multigenic ?Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.
Multigenic or multifactor ?Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.
Other Names (AKA)
GAMT deficiency; Cerebral creatine deficiency syndrome 2
Congenital and Genetic Diseases; Metabolic disorders; Nervous System Diseases
Guanidinoacetate methyltransferase (GAMT) deficiency is an
GAMT deficiency is caused by changes (
Symptoms of GAMT deficiency may worsen with age if a person is undiagnosed and does not receive the necessary treatment.
This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.
|Medical Terms||Other Names||
|30%-79% of people have these symptoms|
|Intellectual disability, severe||
Early and severe mental retardation
Mental retardation, severe
Severe mental retardation
[ more ]
|Progressive extrapyramidal movement disorder||0007153|
|Severe global developmental delay||0011344|
|5%-29% of people have these symptoms|
|Abnormal head movements||0002457|
[ more ]
Involuntary writhing movements in fingers, hands, toes, and feet
|Bilateral tonic-clonic seizure||
Grand mal seizures
|Focal impaired awareness seizure||0002384|
|Generalized myoclonic seizure||0002123|
More active than typical
|1%-4% of people have these symptoms|
Low or weak muscle tone
|Percent of people who have these symptoms is not available through HPO|
|Delayed speech and language development||
Deficiency of speech development
Delayed language development
Delayed speech acquisition
Delayed speech development
Impaired speech and language development
Impaired speech development
Language development deficit
Late-onset speech development
Poor language development
Speech and language delay
Speech and language difficulties
[ more ]
|Global developmental delay||0001263|
|Infantile muscular hypotonia||
Decreased muscle tone in infant
Mental retardation, nonspecific
[ more ]
|Reduced brain creatine level by MRS||0025051|
- The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
People with GAMT deficiency may also be on a diet that restricts their arginine or
Doctors will recommend that people affected by GAMT deficiency be monitored closely to see how treatment is working for them. Treatment for GAMT deficiency can keep the symptoms of the disease from progressing, but treatment has not been shown to improve
Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.
Conditions with similar signs and symptoms from Orphanet
The differential diagnosis in children with a cerebral creatine deficiency includes L-Arginine:glycine amidinotransferase (AGAT) deficiency and X-linked creatine transporter deficiency. In the case of a partial cerebral creatine deficiency, argininosuccinic aciduria, citrullinemia type I, and gyrate atrophy of the choroid and retina (see these terms) should be considered.
Visit the Orphanet disease page for more information.
Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.
These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.
- Genetics Home Reference (GHR) contains information on Guanidinoacetate methyltransferase deficiency. This website is maintained by the National Library of Medicine.
- GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
- The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
- Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
- Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
- PubMed is a searchable database of medical literature and lists journal articles that discuss Guanidinoacetate methyltransferase deficiency. Click on the link to view a sample search on this topic.
- Guanidinoacetate methyltransferase deficiency. Genetics Home Reference. June 2015; https://ghr.nlm.nih.gov/condition/guanidinoacetate-methyltransferase-deficiency.
- Mercimek-Mahmutoglu S, Salomons GS. Creatine Deficiency Syndromes. GeneReviews. Updated Dec. 10, 2015; https://www.ncbi.nlm.nih.gov/books/NBK3794.
- Stockler-Ipsiroglu S, van Karnebeek C, Longo N, Korenke GC, Mercimek-Mahmutoglu S, Marquart I, Barshop B, Grolik C, Schlune A, Angle B, Araujo 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, and Schulze A. Guanidinoacetate methyltransferase (GAMT) deficiency: outcomes in 48 individuals and recommendations for diagnosis, treatment, and monitoring. Molecular Genetics and Metabolism.. January 2014; 111(1):16-25. https://www.ncbi.nlm.nih.gov/pubmed/24268530.
- Cerebral Creatine Deficiency Syndrome2; CCDS2. Online Mendelian Inheritance in Man. June 18, 2014; https://www.omim.org/entry/612736.
- Iqbal F. Review: Human guanidinoacetate n-methyl transferase (GAMT) deficiency: A treatable inborn error of metabolism. Pakistan Journal of Pharmaceutical Sciences. November 2015; 28(6):2207-2211. https://www.ncbi.nlm.nih.gov/pubmed/26639513.
- Stockler S. Guanidinoacetate methyltransferase deficiency. Orphanet. December 2014; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=382.
- Mercimek-Mahmutoglu S, Pop A, Kanhai W, Fernandez Ojeda M, Holwerda U, Smith D, Loeber JG, Schielen PC, and Salomons GC. A pilot study to estimate incidence of guanidinoacetate methyltransferase deficiency in newborns by direct sequencing of the GAMT gene. Gene. January 2016; 575(1):127-131. https://www.ncbi.nlm.nih.gov/pubmed/26319512.
- Ombrone D, Giocaliere E, Forni G, Malvagia S, and Ia Marca G. Expanded newborn screening by mass spectrometry: New tests, future perspectives. Mass Spectrometry Reviews. January-February 2016; 35(1):71-84. https://www.ncbi.nlm.nih.gov/pubmed/25952022.
- Pitt JJ, Tzanakos N, and Nguyen T. Newborn screening for guanidinoacetate methyl transferase deficiency. Molecular Genetics and Metabolism. March 2014; 111(3):303-304. https://www.ncbi.nlm.nih.gov/pubmed/24477282.
- Pasquali M, Schwarz E, Jensen M, Yuzyuk T, DeBiase I, Randall H, and Longo N. Feasibility of newborn screening for guanidinoacetate methyltransferase (GAMT) deficiency. Journal of Inherited Metabolic Disease. March 2014; 37(2):231-236. https://www.ncbi.nlm.nih.gov/pubmed/24276113.