DeCure for Guanidinoacetate methyltransferase deficiency
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for guanidinoacetate methyltransferase deficiency — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleGuanidinoacetate methyltransferase deficiency maps to a 1-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
approvedCreatineApproved drug
Structures already discussed alongside guanidinoacetate methyltransferase deficiency in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
creatininase-product complex — Creatine has a real, experimentally solved structure in complex with this target (PDB 1V7Z, 1.6 Å). This is the drug's own deposited structure, not a prediction, and confirms it is a structurally characterised molecule rather than an untested guess.
Loading structure…
helix sheet crndrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 1V7Z · 1.6 Å · ligand Creatine (CRN). Experimental structure, not a prediction.
What the evidence adds up to
Guanidinoacetate methyltransferase deficiency (GAMT) is an autosomal recessive inborn error of metabolism caused by a pathogenic variant in the GAMT gene on chromosome 19p13.3. Estimated prevalence can be as high as 1 in 2,640,000, and countries such as Saudi Arabia may have a higher prevalence due to high consanguinity rates. A scoping review of 53 cases and a case series of four novel Saudi Arabian patients, published in 2022, reported that 53% of patients were male and 47% female, with age of onset ranging from 8 to 31 months. Fifty percent of cases were infants at onset, 28% toddlers, and 15% children; 79% developed symptoms before five years old. Among the 53 reviewed cases, 68% developed generalised seizures over their lifetime, 84% expressed some form of developmental delay, and 43% had intellectual disabilities or mental retardation severe enough to require special care. Twenty-three percent of affected cases came from consanguineous marriages, and 7% had affected relatives.
The four novel cases from Saudi Arabia were the first reported in that country. Seizure was a leading finding in the majority of cases, developmental delay was broadly observed, and intellectual delay with language impairment were described as primary hallmarks. The authors recommend early diagnosis and suggest that premarital testing of neurogenetic diseases using whole-exome sequencing may be a future direction, particularly in populations with high consanguinity. No treatment data, no drug repurposing evidence, and no interventional trial results are presented in these abstracts.
What remains missing is any controlled trial of a therapy for GAMT deficiency, any biomarker-stratified patient cohort, and any funding for a prospective treatment study. The evidence here is purely descriptive epidemiology and case reporting; no drug, no survival curve, no response rate is available to assess.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of Inherited Metabolic Disease · 2006 · 31 citations · open access
Guanidinoacetate methyltransferase deficiency masquerading as a mitochondrial encephalopathy
AbstractGuanidinoacetate methyltransferase (GAMT) deficiency is a rare disorder of creatine synthesis. We report a patient who presented at 10 months of age with hypotonia and global developmental delay. Subsequently, she developed seizures and choreoathetosis. Magnetic resonance imaging showed high signal bilaterally in the globus pallidus on T2-weighted images. Mitochondrial respiratory chain studies revealed low complex I activity (in muscle 0.052 nmol NADH oxidized per min per unit citrate synthase, controls 0.166 +/- 0.047; in fibroblasts 0.080 nmol NADH oxidized per min per unit citrate synthase, controls 0.197 +/- 0.034). The true diagnosis was suspected at 21 months of age because of persistent low plasma and urine creatinine concentrations. GAMT activity was undetectable in fibroblasts and compound heterozygous mutations were found in the GAMT gene (c.327G>A and c.522G>A). The patient was treated with creatine, dietary arginine restriction and ornithine supplements. Her movement disorder and seizures resolved but she still has severe cognitive impairment and no expressive language. The occurrence of secondary respiratory chain abnormalities in GAMT deficiency may lead to misdiagnosis, particularly as the clinical and radiological features resemble those seen in mitochondrial encephalopathies. It is important to establish the correct diagnosis because specific treatment is available.
Journal of Microscopy and Ultrastructure · 2022 · 2 citations · open access
Phenotypic and Molecular Spectrum of Guanidinoacetate N-Methyltransferase Deficiency: An Analytical Study of a Case Series and a Scoping Review of 53 Cases of Guanidinoacetate N-Methyltransferase
AbstractAbstract Background: Guanidinoacetate methyltransferase deficiency (GAMT) is an autosomal recessive inborn error of metabolism. A condition that results from a pathogenic variant in the GAMT gene that maps to 19p13.3. The prevalence can be estimated to be up to 1:2,640,000 cases; countries such as Saudi Arabia could have a higher prevalence due to high consanguinity rates. The clinical manifestations that a patient could obtain are broad and start to manifest in the patients’ early childhood years. Materials and Methods: A thorough review of case reports in January 2022 was conducted. The retrieved literature was screened for demographic data. Patients of all ages were included. Qualitative variables were described as number and percentage (%), and quantitative data were described by the mean and standard deviation. In bivariate data, Chi-square test (χ 2 ) was used and t -test for nonparametric variables. Results: Gender distribution was 53% of males and 47% females. Reported age ranged from 8 to 31 months. At the age of onset, 50% of the cases were infants, 28% were toddlers, and 15% were children, concluding that 79% of the reported cases developed symptoms before 5 years old. 68% of the cases developed generalized seizures throughout their life. 84% of the cases expressed a form of developmental delay. 43% of the cases had intellectual disabilities and mental retardation that affected their learning process; most cases required special care. 23% of the affected cases were of consanguineous marriages, and 7% had affected relatives. Conclusion: We described four novel case reports, the first to be reported in Saudi Arabia. Seizure was a leading finding in the majority of the cases. Developmental delay was broadly observed. Intellectual delay and language impairments are primary hallmarks. Further understanding and early diagnosis are recommended. Premarital testing of neurogenetic diseases using whole-exome sequencing is probably a future direction, especially in populations with high consanguinity rates.
AbstractThe attached file is a CARE checklist used for a research project entitled "<em>Phenotypic and Molecular Spectrum of Guanidinoacetate N-Methyltransferase deficiency: An Analytical Study of a Case Series and a Scoping Review of 53 Cases of Guanidinoacetate N-Methyltransferase</em>". The research article is authored by Anas S. Alyazidi<sup>1</sup>, Osama Y. Muthaffar<sup>2</sup>, Mohammed K. Shawli<sup>1</sup>, Yara F. Aljefri<sup>1</sup>, Renad A. Ahmed<sup>1</sup>, Layan S. Baaishrah3, Abdulaziz T. Jambi<sup>1</sup>, Fahad A. Alotibi<sup>1</sup>. <br> <sup>1 </sup>Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia <sup>2</sup> Department of Pediatrics, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia <sup>3</sup> Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia
AbstractThe attached file is a PRISMA checklist used for a research project entitled "<em>Phenotypic and Molecular Spectrum of Guanidinoacetate N-Methyltransferase deficiency: An Analytical Study of a Case Series and a Scoping Review of 53 Cases of Guanidinoacetate N-Methyltransferase</em>". The research article is authored by Anas S. Alyazidi<sup>1</sup>, Osama Y. Muthaffar<sup>2</sup>, Mohammed K. Shawli<sup>1</sup>, Yara F. Aljefri<sup>1</sup>, Renad A. Ahmed<sup>1</sup>, Layan S. Baaishrah<sup>3</sup>, Abdulaziz T. Jambi<sup>1</sup>, Fahad A. Alotibi<sup>1</sup>. <br> <sup>1 </sup>Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia <sup>2</sup> Department of Pediatrics, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia <sup>3</sup> Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia
AbstractThe attached file is a PRISMA checklist used for a research project entitled "<em>Phenotypic and Molecular Spectrum of Guanidinoacetate N-Methyltransferase deficiency: An Analytical Study of a Case Series and a Scoping Review of 53 Cases of Guanidinoacetate N-Methyltransferase</em>". The research article is authored by Anas S. Alyazidi<sup>1</sup>, Osama Y. Muthaffar<sup>2</sup>, Mohammed K. Shawli<sup>1</sup>, Yara F. Aljefri<sup>1</sup>, Renad A. Ahmed<sup>1</sup>, Layan S. Baaishrah<sup>3</sup>, Abdulaziz T. Jambi<sup>1</sup>, Fahad A. Alotibi<sup>1</sup>. <br> <sup>1 </sup>Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia <sup>2</sup> Department of Pediatrics, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia <sup>3</sup> Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia
AbstractThe attached file is a CARE checklist used for a research project entitled "<em>Phenotypic and Molecular Spectrum of Guanidinoacetate N-Methyltransferase deficiency: An Analytical Study of a Case Series and a Scoping Review of 53 Cases of Guanidinoacetate N-Methyltransferase</em>". The research article is authored by Anas S. Alyazidi<sup>1</sup>, Osama Y. Muthaffar<sup>2</sup>, Mohammed K. Shawli<sup>1</sup>, Yara F. Aljefri<sup>1</sup>, Renad A. Ahmed<sup>1</sup>, Layan S. Baaishrah3, Abdulaziz T. Jambi<sup>1</sup>, Fahad A. Alotibi<sup>1</sup>. <br> <sup>1 </sup>Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia <sup>2</sup> Department of Pediatrics, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia <sup>3</sup> Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
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