Guanidinoacetate methyltransferase deficiency

A hereditary autosomal recessive error of CREATINE synthesis characterized by language development disorders, DEVELOPMENTAL DISABILITIES; INTELLECTUAL DISABILITY; SEIZURES; ATAXIA; MUSCLE SPASTICITY, severe depletion of creatine/PHOSPHOCREATINE in the brain, and accumulation of guanidinoacetic acid (GAA) in brain and body fluids. Mutations in the GAMT gene have been identified. OMIM: 612736

Also Known As:

Networked: 123 relevant articles (5 outcomes, 3 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Intellectual Disability (Idiocy)
2.	Epilepsy (Aura)
3.	Seizures (Absence Seizure)
4.	Guanidinoacetate methyltransferase deficiency
5.	Movement Disorders (Movement Disorder)

Experts

1.	Salomons, Gajja S: 13 articles (05/2018 - 02/2003)
2.	Wyse, Angela T S: 9 articles (11/2019 - 06/2003)
3.	Schulze, Andreas: 8 articles (06/2022 - 01/2002)
4.	Salomons, G S: 8 articles (01/2016 - 03/2005)
5.	Jakobs, C: 7 articles (11/2012 - 12/2000)
6.	Zugno, Alexandra I: 7 articles (09/2008 - 06/2003)
7.	Leuzzi, Vincenzo: 6 articles (06/2022 - 01/2006)
8.	Longo, Nicola: 6 articles (12/2021 - 02/2011)
9.	Mercimek-Mahmutoglu, Saadet: 6 articles (12/2015 - 01/2004)
10.	Wajner, Moacir: 6 articles (09/2008 - 06/2003)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Guanidinoacetate methyltransferase deficiency:

1.	CreatineIBA 06/09/2022 - "Gene therapy for guanidinoacetate methyltransferase deficiency restores cerebral and myocardial creatine while resolving behavioral abnormalities." 04/01/2022 - "Three GAMT deficiency and one CTD patient reported neurodevelopmental improvement and good seizure control after creatine supplementation. " 09/01/2021 - "This manuscript reports the identification of two infants with GAMT deficiency (one of the cerebral creatine deficiency syndromes) by newborn screening and demonstrates NBS feasibility using a variety of methods." 01/01/2021 - "Guanidinoacetate methyltransferase deficiency (GAMT-D) is one of three cerebral creatine (Cr) deficiency syndromes due to pathogenic variants in the GAMT gene (19p13.3). " 05/01/2020 - "Case Series of Creatine Deficiency Syndrome due to Guanidinoacetate Methyltransferase Deficiency."
2.	glycocyamineIBA 01/01/2016 - "This review also addresses the question of guanidinoacetate toxicity for brain cells, as probably found under GAMT deficiency." 07/01/2015 - "Mild guanidinoacetate increase under partial guanidinoacetate methyltransferase deficiency strongly affects brain cell development." 10/01/2014 - "Guanidinoacetate is of particular interest as a well-known potent epileptogenic compound in guanidinoacetate methyltransferase deficiency. " 03/01/2014 - "With second tier testing, only the samples from GAMT deficiency patients had elevated concentration of guanidinoacetate. " 06/01/2013 - "We report elevation of guanidinoacetate in archived newborn dried blood spots for 3 cases (2 families) of GAMT deficiency compared with an unaffected carrier and controls. "
3.	X-linked Creatine deficiencyIBA 12/13/2012 - "Three additional affected sibs were further identified after familial inquiry (1 brother with GAMT deficiency and 2 brothers with SLC6A8 deficiency in two different families). " 03/01/2010 - "Patients with guanidinoacetate methyltransferase deficiency or creatine transporter deficiency may exhibit autistic behavior. " 01/01/2002 - "Oral creatine supplementation improved the clinical symptoms in both AGAT and GAMT deficiency, but not in creatine transporter deficiency. " 01/01/2023 - "These findings stress the role of substantially elevated GAA as a primary neurotoxic agent in GAMT deficiency and we discuss the potential role of GAA in arginase (and creatine transporter) deficiency which show a much more modest increase in GAA concentrations yet share the unique hyperexcitability neuropathology with GAMT deficiency. " 04/01/2022 - "Thirteen patients were eligible [8 creatine transporter deficiency (CTD), 4 guanidinoacetate methyltransferase (GAMT) deficiency and 1 could not be classified]. "
4.	Biomarkers (Surrogate Marker)IBA 01/01/2022 - "Because there are reliable biomarkers for GAMT deficiency, GUAC and CRE, and because the disorder is readily treatable with a significant improvement in outcomes, GAMT deficiency is an excellent candidate for newborn screening. " 01/01/2023 - "The LC-MS/MS method was capable of simultaneously detecting second-tier biomarkers for maple syrup urine disease, homocystinuria, methylmalonic acidemia, propionic acidemia, glutaric acidemia type 1, glutaric acidemia type 2, guanidinoacetate methyltransferase deficiency, short-chain acyl-CoA dehydrogenase deficiency, adrenoleukodystrophy, and Pompe disease."
5.	Guanidinoacetate N-Methyltransferase (Guanidinoacetate Methyltransferase)IBA 03/01/2005 - "Our study describes the adult clinical and biochemical spectrum of guanidinoacetate methyltransferase (GAMT) deficiency, a recently discovered inborn error of metabolism. " 01/07/2022 - "However, increased GAA content in rodents affected by guanidinoacetate methyltransferase (GAMT) deficiency might be responsible for their spared muscle function. " 05/01/2018 - "Guanidinoacetate methyltransferase (GAMT) deficiency is an autosomal recessive disorder caused by pathogenic variants in GAMT. " 01/01/2016 - "A three-tier algorithm for guanidinoacetate methyltransferase (GAMT) deficiency newborn screening." 03/01/2014 - "Feasibility of newborn screening for guanidinoacetate methyltransferase (GAMT) deficiency."
6.	OrnithineIBA 05/30/2023 - "A low-protein diet, Cr and, ornithine were useful for patients with GAMT deficiency. " 01/01/2012 - "However, the identification of additional cases of GAMT deficiency should help elucidate such relationships and the progress of patients treated with creatine in conjunction with ornithine supplementation." 12/01/2001 - "Arginine restriction in combination with ornithine supplementation represents a new and rationale therapeutic approach in GAMT deficiency." 07/01/2014 - "Guanidinoacetate-reducing strategies (high-dose ornithine, arginine-restricted diet) are additionally employed in GAMT deficiency. " 02/01/2003 - "Treatment of combined arginine restriction and ornithine substitution in GAMT deficiency is capable to decrease guanidinoacetic acid permanently and improves the clinical outcome. "
7.	Sodium BenzoateFDA Link 07/01/2014 - "Case study for the evaluation of current treatment recommendations of guanidinoacetate methyltransferase deficiency: ineffectiveness of sodium benzoate." 12/01/2023 - "Treatment options for GAMT deficiency include creatine supplementation, ornithine supplementation, arginine restriction, and sodium benzoate supplementation. " 11/01/2013 - "Our results show that supplements of creatine, sodium benzoate (to reduce glycine) and ornithine reduce guanidinoacetate levels in patients with GAMT deficiency (dietary therapy was not evaluated in our study). "
8.	Adenosine Triphosphatases (ATPase)IBA 03/01/2006 - "Considering the importance of Na+, K+-ATPase and CK activities for brain metabolism homeostasis, our results suggest that the inhibition of these enzymes by increased intracerebral levels of GAA may contribute to the neuropathology observed in patients with GAMT-deficiency." 06/01/2003 - "It is proposed that Na(+), K(+)-ATPase inhibition by guanidinoacetate may be one of the mechanisms involved in the neuronal dysfunction observed in GAMT-deficiency and in other diseases which accumulate guanidinoacetate." 09/01/2010 - "Previous reports have shown that GAA alters brain energy metabolism and that creatine, which is depleted in patients with GAMT deficiency, can act as a neuroprotector; as such, in the present study we investigated the effect of creatine administration on some of the altered parameters of energy metabolism (complex II, Na(+),K(+)-ATPase and creatine kinase) and lipid peroxidation caused by intrastriatal administration of GAA in adult rats. " 06/01/2003 - "The aim of this work was to investigate the effect of guanidinoacetate (GAA), the principal metabolite accumulating in guanidinoacetate methyltransferase (GAMT)-deficiency, on Na(+), K(+)-ATPase, Mg(2+)-ATPase and acetylcholinesterase (AChE) activities in striatum of young rats. "
9.	Glycine (Aminoacetic Acid)FDA LinkGeneric 11/01/2013 - "Our results show that supplements of creatine, sodium benzoate (to reduce glycine) and ornithine reduce guanidinoacetate levels in patients with GAMT deficiency (dietary therapy was not evaluated in our study). " 03/01/2023 - "While all 3 disorders are currently treated with creatine supplementation, guanidinoacetate methyltransferase deficiency is also treated with ornithine supplementation and a protein- or arginine-restricted diet, and creatine transporter deficiency is treated with arginine and glycine supplementation (with no proven improvements)."
10.	Creatine Kinase (Creatine Phosphokinase)IBA 05/01/2020 - "Coexistence of guanidinoacetate methyltransferase (GAMT) deficiency and neuroleptic malignant syndrome without creatine kinase elevation." 09/01/2010 - "Previous reports have shown that GAA alters brain energy metabolism and that creatine, which is depleted in patients with GAMT deficiency, can act as a neuroprotector; as such, in the present study we investigated the effect of creatine administration on some of the altered parameters of energy metabolism (complex II, Na(+),K(+)-ATPase and creatine kinase) and lipid peroxidation caused by intrastriatal administration of GAA in adult rats. " 05/01/2020 - "We describe the first child with guanidinoacetate methyltransferase (GAMT) deficiency who developed neuroleptic malignant syndrome (NMS) after the treatment of risperidone without elevated creatine kinase (CK) levels. "

Therapies and Procedures

1.	Therapeutics 01/01/2023 - "Although GAMT deficiency is significantly more rare than other conditions included in newborn screening, the feasibility of screening, the low number of positive results, the relative ease of diagnosis, and the expected benefit of presymptomatic dietary therapy led to a recommendation from the Advisory Committee on Heritable Disorders in Newborns and Children to the Secretary of Health and Human Services that GAMT deficiency be added to the Recommended Uniform Screening Panel. " 11/01/2012 - "Pre-symptomatic therapy has shown promising results, especially in GAMT deficiency patients. " 09/01/2021 - "Both infants identified with GAMT deficiency started therapy by 2 weeks of age and are growing and developing normally at 7 (Utah) and 4 (New York) months of age. " 11/01/2013 - "Here we evaluate how different therapies affect plasma guanidinoacetate levels in patients with GAMT deficiency. " 04/01/1998 - "Therapies for guanidinoacetate methyltransferase deficiency and for 3-phosphoglycerated dehydrogenase deficiency appear promising. "
2.	Secondary Prevention 11/01/2013 - "Normal development with early therapy renders GAMT deficiency an ideal candidate for inclusion in newborn screening panels."
3.	Diet Therapy (Therapy, Diet) 02/15/2011 - "Defects of creatine biosynthesis are treated with creatine supplements and, in GAMT deficiency, with ornithine and dietary restriction of arginine through limitation of protein intake. "
4.	Aftercare (After-Treatment) 05/30/2023 - "After treatment, patients with GAMT deficiency showed obvious improvements, and brain creatine (Cr) levels recovered to 50-80% of normal, 1 patient achieved normal neurodevelopment, and 3 patients became epilepsy free; however, 6 male patients with X-linked creatine transporter gene (SLC6A8) variants received Cr for 3-6 months with no effect, and 2 patients received combined therapy with few improvements. "