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Guanidinoacetate methyltransferase deficiency

Reviewed June 2015

What is guanidinoacetate methyltransferase deficiency?

Guanidinoacetate methyltransferase deficiency is an inherited disorder that primarily affects the brain and muscles. Without early treatment, people with this disorder have neurological problems that are usually severe. These problems include intellectual disability, speech development limited to a few words, and recurrent seizures (epilepsy). Affected individuals may also exhibit autistic behaviors that affect communication and social interaction or self-injurious behaviors such as head-banging. Other features of this disorder can include involuntary movements (extrapyramidal dysfunction) such as tremors or facial tics.

People with guanidinoacetate methyltransferase deficiency may have weak muscle tone and delayed development of motor skills such as sitting or walking. In severe cases they may lose previously acquired skills such as the ability to support their head or to sit unsupported.

How common is guanidinoacetate methyltransferase deficiency?

Guanidinoacetate methyltransferase deficiency is a very rare disorder. About 80 affected individuals have been described in the medical literature. Of these, approximately one-third are of Portuguese origin.

What genes are related to guanidinoacetate methyltransferase deficiency?

Mutations in the GAMT gene cause guanidinoacetate methyltransferase deficiency. The GAMT gene provides instructions for making the enzyme guanidinoacetate methyltransferase. This enzyme participates in the two-step production (synthesis) of the compound creatine from the protein building blocks (amino acids) glycine, arginine, and methionine. Specifically, guanidinoacetate methyltransferase controls the second step of this process. In this step, creatine is produced from another compound called guanidinoacetate. Creatine is needed for the body to store and use energy properly.

GAMT gene mutations impair the ability of the guanidinoacetate methyltransferase enzyme to participate in creatine synthesis, resulting in a shortage of creatine. The effects of guanidinoacetate methyltransferase deficiency are most severe in organs and tissues that require large amounts of energy, especially the brain.

Related Gene(s)

Changes in this gene are associated with guanidinoacetate methyltransferase deficiency.

  • GAMT

How do people inherit guanidinoacetate methyltransferase deficiency?

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Where can I find information about diagnosis or management of guanidinoacetate methyltransferase deficiency?

These resources address the diagnosis or management of guanidinoacetate methyltransferase deficiency and may include treatment providers.

  • Gene Review: Creatine Deficiency Syndromes (http://www.ncbi.nlm.nih.gov/books/NBK3794)
  • Genetic Testing Registry: Deficiency of guanidinoacetate methyltransferase (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0574080)

You might also find information on the diagnosis or management of guanidinoacetate methyltransferase deficiency in Educational resources and Patient support.

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about guanidinoacetate methyltransferase deficiency?

You may find the following resources about guanidinoacetate methyltransferase deficiency helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for guanidinoacetate methyltransferase deficiency?

  • creatine deficiency syndrome due to GAMT deficiency
  • deficiency of guanidinoacetate methyltransferase
  • GAMT deficiency

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about guanidinoacetate methyltransferase deficiency?

Ask the Genetic and Rare Diseases Information Center (https://rarediseases.info.nih.gov/gard).

What glossary definitions help with understanding guanidinoacetate methyltransferase deficiency?

acids ; arginine ; autosomal ; autosomal recessive ; cell ; compound ; creatine ; deficiency ; disability ; enzyme ; epilepsy ; extrapyramidal ; gene ; glycine ; inherited ; involuntary ; methionine ; methyltransferase ; motor ; muscle tone ; neurological ; protein ; recessive ; syndrome ; synthesis

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.

References

  • Almeida LS, Vilarinho L, Darmin PS, Rosenberg EH, Martinez-Muñoz C, Jakobs C, Salomons GS. A prevalent pathogenic GAMT mutation (c.59G>C) in Portugal. Mol Genet Metab. 2007 May;91(1):1-6. Epub 2007 Mar 1. (http://www.ncbi.nlm.nih.gov/pubmed/17336114?dopt=Abstract)
  • Béard E, Braissant O. Synthesis and transport of creatine in the CNS: importance for cerebral functions. J Neurochem. 2010 Oct;115(2):297-313. doi: 10.1111/j.1471-4159.2010.06935.x. Epub 2010 Aug 25. Review. (http://www.ncbi.nlm.nih.gov/pubmed/20796169?dopt=Abstract)
  • Braissant O, Henry H, Béard E, Uldry J. Creatine deficiency syndromes and the importance of creatine synthesis in the brain. Amino Acids. 2011 May;40(5):1315-24. doi: 10.1007/s00726-011-0852-z. Epub 2011 Mar 10. Review. (http://www.ncbi.nlm.nih.gov/pubmed/21390529?dopt=Abstract)
  • Braissant O. GAMT deficiency: 20 years of a treatable inborn error of metabolism. Mol Genet Metab. 2014 Jan;111(1):1-3. doi: 10.1016/j.ymgme.2013.11.002. Epub 2013 Nov 10. (http://www.ncbi.nlm.nih.gov/pubmed/24275206?dopt=Abstract)
  • OMIM: CEREBRAL CREATINE DEFICIENCY SYNDROME 2 (http://omim.org/entry/612736)
  • Dhar SU, Scaglia F, Li FY, Smith L, Barshop BA, Eng CM, Haas RH, Hunter JV, Lotze T, Maranda B, Willis M, Abdenur JE, Chen E, O'Brien W, Wong LJ. Expanded clinical and molecular spectrum of guanidinoacetate methyltransferase (GAMT) deficiency. Mol Genet Metab. 2009 Jan;96(1):38-43. doi: 10.1016/j.ymgme.2008.10.008. Epub 2008 Nov 21. (http://www.ncbi.nlm.nih.gov/pubmed/19027335?dopt=Abstract)
  • El-Gharbawy AH, Goldstein JL, Millington DS, Vaisnins AE, Schlune A, Barshop BA, Schulze A, Koeberl DD, Young SP. Elevation of guanidinoacetate in newborn dried blood spots and impact of early treatment in GAMT deficiency. Mol Genet Metab. 2013 Jun;109(2):215-7. doi: 10.1016/j.ymgme.2013.03.003. Epub 2013 Mar 16. (http://www.ncbi.nlm.nih.gov/pubmed/23583224?dopt=Abstract)
  • Gordon N. Guanidinoacetate methyltransferase deficiency (GAMT). Brain Dev. 2010 Feb;32(2):79-81. doi: 10.1016/j.braindev.2009.01.008. Epub 2009 Mar 16. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19289269?dopt=Abstract)
  • Mercimek-Mahmutoglu S, Ndika J, Kanhai W, de Villemeur TB, Cheillan D, Christensen E, Dorison N, Hannig V, Hendriks Y, Hofstede FC, Lion-Francois L, Lund AM, Mundy H, Pitelet G, Raspall-Chaure M, Scott-Schwoerer JA, Szakszon K, Valayannopoulos V, Williams M, Salomons GS. Thirteen new patients with guanidinoacetate methyltransferase deficiency and functional characterization of nineteen novel missense variants in the GAMT gene. Hum Mutat. 2014 Apr;35(4):462-9. doi: 10.1002/humu.22511. Epub 2014 Mar 6. (http://www.ncbi.nlm.nih.gov/pubmed/24415674?dopt=Abstract)
  • Mercimek-Mahmutoglu S, Sinclair G, van Dooren SJ, Kanhai W, Ashcraft P, Michel OJ, Nelson J, Betsalel OT, Sweetman L, Jakobs C, Salomons GS. Guanidinoacetate methyltransferase deficiency: first steps to newborn screening for a treatable neurometabolic disease. Mol Genet Metab. 2012 Nov;107(3):433-7. doi: 10.1016/j.ymgme.2012.07.022. Epub 2012 Aug 3. (http://www.ncbi.nlm.nih.gov/pubmed/23031365?dopt=Abstract)
  • Nasrallah F, Feki M, Kaabachi N. Creatine and creatine deficiency syndromes: biochemical and clinical aspects. Pediatr Neurol. 2010 Mar;42(3):163-71. doi: 10.1016/j.pediatrneurol.2009.07.015. Review. (http://www.ncbi.nlm.nih.gov/pubmed/20159424?dopt=Abstract)
  • Pasquali M, Schwarz E, Jensen M, Yuzyuk T, DeBiase I, Randall H, Longo N. Feasibility of newborn screening for guanidinoacetate methyltransferase (GAMT) deficiency. J Inherit Metab Dis. 2014 Mar;37(2):231-6. doi: 10.1007/s10545-013-9662-7. Epub 2013 Nov 26. (http://www.ncbi.nlm.nih.gov/pubmed/24276113?dopt=Abstract)
  • 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 Jan;111(1):16-25. doi: 10.1016/j.ymgme.2013.10.018. Epub 2013 Nov 7. (http://www.ncbi.nlm.nih.gov/pubmed/24268530?dopt=Abstract)
  • Stockler-Ipsiroglu S, van Karnebeek CD. Cerebral creatine deficiencies: a group of treatable intellectual developmental disorders. Semin Neurol. 2014 Jul;34(3):350-6. doi: 10.1055/s-0034-1386772. Epub 2014 Sep 5. Review. Erratum in: Semin Neurol. 2014 Sep;34(4):479. (http://www.ncbi.nlm.nih.gov/pubmed/25192512?dopt=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 Nov;110(3):255-62. doi: 10.1016/j.ymgme.2013.08.020. Epub 2013 Sep 8. (http://www.ncbi.nlm.nih.gov/pubmed/24071436?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: June 2015
Published: June 29, 2015