Guanidinoacetate methyltransferase (GAMT) deficiency, a cerebral creatine deficiency syndrome: A rare treatable metabolic disorder

Yoganathan, Sangeetha; Arunachal, Gautham; Kratz, Lisa E.; Varman, Mugil; Sudhakar, Sniya; Oommen, Samuel Philip; Jain, Shikha; Thomas, Maya; Babuji, Manimegalai

doi:10.4103/aian.aian_172_19

Cited by 4 publications

(8 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The most common symptoms of GAMT deficiency are epilepsy and global developmental delay, often affecting cognitive, speech/language, and behavioral functioning [ 2 , 4 , 8 , [12] , [13] , [14] , 17 , 22 , 23 ]. Many reports have also reported that epilepsy is resistant to treatment, likely due to the high levels of GAA accumulation [ 4 , 12 , 24 ].…”

Section: Discussionmentioning

confidence: 99%

“…Many reports have also reported that epilepsy is resistant to treatment, likely due to the high levels of GAA accumulation [ 4 , 12 , 24 ]. Neurological manifestations can also include attention-deficit/hyperactivity disorder, impulsive behavior, and autistic traits [ 4 , 12 , 13 , 17 , 22 ]. Other symptoms noted are constipation and extrapyramidal movement disorders including but not limited to hypotonia/dystonia, rigidity, and impaired reflexes [ 2 , 4 , 8 , 12 , 14 , 17 , 22 , 23 ].…”

Section: Discussionmentioning

confidence: 99%

“…Neurological manifestations can also include attention-deficit/hyperactivity disorder, impulsive behavior, and autistic traits [ 4 , 12 , 13 , 17 , 22 ]. Other symptoms noted are constipation and extrapyramidal movement disorders including but not limited to hypotonia/dystonia, rigidity, and impaired reflexes [ 2 , 4 , 8 , 12 , 14 , 17 , 22 , 23 ]. In accordance with these movement symptoms, brain MRI can show T2 hyperintensity of the bilateral globus pallidi, and CT imaging can show calcification of the same region, however, this is not always present [ 4 , [12] , [13] , [14] , 18 , 22 ].…”

Section: Discussionmentioning

confidence: 99%

“…Other symptoms noted are constipation and extrapyramidal movement disorders including but not limited to hypotonia/dystonia, rigidity, and impaired reflexes [ 2 , 4 , 8 , 12 , 14 , 17 , 22 , 23 ]. In accordance with these movement symptoms, brain MRI can show T2 hyperintensity of the bilateral globus pallidi, and CT imaging can show calcification of the same region, however, this is not always present [ 4 , [12] , [13] , [14] , 18 , 22 ]. After ruling out other genetic causes, 1 study reported a patient with recurrent bone fractures which was attributed to the sedentary nature of the disease due to their motor symptoms [17] .…”

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Guanidinoacetate N-methyltransferase deficiency: Case report and brief review of the literature

Libell,

Lakhani,

Balar

et al. 2023

Radiology Case Reports

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Guanidinoacetate N-methyltransferase deficiency: Case report and brief review of the literature

Libell,

Lakhani,

Balar

et al. 2023

Radiology Case Reports

View full text Add to dashboard Cite

“…To date, the majority of clinical trials investigating the therapeutic potential of creatine supplementation in pediatric populations have focused on creatine (and/or creatine transporter) deficiencies, inborn errors of metabolism, neuromuscular disorders, and myopathies [ 9 , 44 , 45 , 46 , 47 , 48 , 49 ]. Guanidinoacetate methyltransferase (GAMT) and arginine:glycine amidinotransferase (AGAT) deficiency, are types of inborn errors of creatine metabolism, collectively characterized as cerebral creatine synthesis deficiencies [ 47 , 50 ]. Several studies and case reports have indicated that creatine supplementation can restore tissue creatine content and improve some of the symptoms resulting from creatine deficiencies [ 51 , 52 , 53 , 54 ].…”

Section: Clinical Applicationsmentioning

confidence: 99%

Creatine Supplementation in Children and Adolescents

Jagim

Kerksick

2021

Nutrients

View full text Add to dashboard Cite

Creatine is a popular ergogenic aid among athletic populations with consistent evidence indicating that creatine supplementation also continues to be commonly used among adolescent populations. In addition, the evidence base supporting the therapeutic benefits of creatine supplementation for a plethora of clinical applications in both adults and children continues to grow. Among pediatric populations, a strong rationale exists for creatine to afford therapeutic benefits pertaining to multiple neuromuscular and metabolic disorders, with preliminary evidence for other subsets of clinical populations as well. Despite the strong evidence supporting the efficacy and safety of creatine supplementation among adult populations, less is known as to whether similar physiological benefits extend to children and adolescent populations, and in particular those adolescent populations who are regularly participating in high-intensity exercise training. While limited in scope, studies involving creatine supplementation and exercise performance in adolescent athletes generally report improvements in several ergogenic outcomes with limited evidence of ergolytic properties and consistent reports indicating no adverse events associated with supplementation. The purpose of this article is to summarize the rationale, prevalence of use, performance benefits, clinical applications, and safety of creatine use in children and adolescents.

show abstract

Intellectual Disability and Brain Creatine Deficit: Phenotyping of the Genetic Mouse Model for GAMT Deficiency

Rossi

Nardecchia

Pierigé

et al. 2021

Genes

View full text Add to dashboard Cite

Guanidinoacetate methyltransferase deficiency (GAMT-D) is one of three cerebral creatine (Cr) deficiency syndromes due to pathogenic variants in the GAMT gene (19p13.3). GAMT-D is characterized by the accumulation of guanidinoacetic acid (GAA) and the depletion of Cr, which result in severe global developmental delay (and intellectual disability), movement disorder, and epilepsy. The GAMT knockout (KO) mouse model presents biochemical alterations in bodily fluids, the brain, and muscles, including increased GAA and decreased Cr and creatinine (Crn) levels, which are similar to those observed in humans. At the behavioral level, only limited and mild alterations have been reported, with a large part of analyzed behaviors being unaffected in GAMT KO as compared with wild-type mice. At the cerebral level, decreased Cr and Crn and increased GAA and other guanidine compound levels have been observed. Nevertheless, the effects of Cr deficiency and GAA accumulation on many neurochemical, morphological, and molecular processes have not yet been explored. In this review, we summarize data regarding behavioral and cerebral GAMT KO phenotypes, and focus on uncharted behavioral alterations that are comparable with the clinical symptoms reported in GAMT-D patients, including intellectual disability, poor speech, and autistic-like behaviors, as well as unexplored Cr-induced cerebral alterations.

show abstract

Guanidinoacetate methyltransferase (GAMT) deficiency, a cerebral creatine deficiency syndrome: A rare treatable metabolic disorder

Cited by 4 publications

References 11 publications

Guanidinoacetate N-methyltransferase deficiency: Case report and brief review of the literature

Guanidinoacetate N-methyltransferase deficiency: Case report and brief review of the literature

Creatine Supplementation in Children and Adolescents

Intellectual Disability and Brain Creatine Deficit: Phenotyping of the Genetic Mouse Model for GAMT Deficiency

Contact Info

Product

Resources

About