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AGAT Deficiency

AGAT Deficiency (GATM-related creatine synthesis defect) — Comprehensive Disease Characteristics Report

2026-05-02
Falcon MONDO:0012996 Model: Edison Scientific Literature 52 citations

AGAT Deficiency (GATM-related creatine synthesis defect) — Comprehensive Disease Characteristics Report

Target disease: AGAT Deficiency (autosomal recessive creatine biosynthesis disorder; a cerebral creatine deficiency disorder). (mulik2023creatinedeficiencydisorders pages 2-3, longo2011disordersofcreatine pages 2-3)

Key recent sources prioritized: - ClinGen CCDS Variant Curation Expert Panel (VCEP) specifications for GATM variant interpretation (May 2024). (goldstein2024clingenvariantcuration pages 3-4) - Review of creatine deficiency disorders (Mar 2023). (mulik2023creatinedeficiencydisorders pages 2-3) - CCDS diagnostic implementation statistics (Swiss laboratory study, Jan 2025). (kaufman2025diagnosticdelayin pages 1-2) - MRS case report demonstrating treatment response (Dec 2024). (garg2024magneticresonancespectroscopy pages 2-4)

1. Disease Information

1.1 Definition / overview

AGAT deficiency is an ultrarare inborn error of creatine biosynthesis caused by biallelic loss-of-function variants in GATM, encoding L-arginine:glycine amidinotransferase (AGAT), the first step in creatine synthesis. It causes cerebral creatine deficiency detectable by proton magnetic resonance spectroscopy (1H-MRS) and a neurodevelopmental phenotype (developmental delay/intellectual disability with prominent speech-language impairment), often with myopathy/proximal weakness. (edvardson2010larginineglycineamidinotransferase(agat) pages 1-2, stockleripsiroglu2015arginineglycineamidinotransferase(agat) pages 1-2, longo2011disordersofcreatine pages 2-3)

1.2 Key identifiers and ontologies

Not retrieved in this tool run (needs external lookup to complete): Orphanet ID, MeSH ID, ICD-10/ICD-11 codes.

1.3 Synonyms / alternative names

  • L-arginine:glycine amidinotransferase deficiency (edvardson2010larginineglycineamidinotransferase(agat) pages 1-2, stockleripsiroglu2015arginineglycineamidinotransferase(agat) pages 1-2)
  • GATM-related creatine deficiency / creatine synthesis defect (stockleripsiroglu2015arginineglycineamidinotransferase(agat) pages 1-2)
  • Cerebral creatine deficiency disorder/syndrome (CCDD/CCDS), enzyme-defect subgroup (kaufman2025diagnosticdelayin pages 1-2)

Note: The synonym “cerebral creatine deficiency syndrome 3” appears in a CCDS case-report context (garg2024magneticresonancespectroscopy pages 2-4) but was not consistently used across the core genetics/biochemical literature retrieved here.

1.4 Evidence sources (patient-level vs aggregated)

Most clinical knowledge is derived from individual case reports and small case series (e.g., 16 patients worldwide in a 2015 cohort) and synthesized in reviews and expert-consensus variant interpretation guidance (ClinGen VCEP). (stockleripsiroglu2015arginineglycineamidinotransferase(agat) pages 1-2, goldstein2024clingenvariantcuration pages 3-4)

2. Etiology

2.1 Disease causal factors

Primary cause: biallelic pathogenic variants in GATM leading to deficient AGAT enzyme activity (loss of function), impairing endogenous creatine synthesis. (mulik2023creatinedeficiencydisorders pages 2-3, goldstein2024clingenvariantcuration pages 3-4)

Authoritative expert consensus (ClinGen VCEP, 2024): the panel “determined loss-of-function is the disease mechanism” for GATM and applies the ACMG/AMP PVS1 framework to null variants expected to undergo NMD. (goldstein2024clingenvariantcuration pages 3-4)

2.2 Risk factors

No specific environmental/exogenous risk factors were identified in the retrieved evidence; AGAT deficiency is primarily a Mendelian enzymatic disorder.

2.3 Protective factors

No validated protective genetic variants or environmental protective factors were identified in the retrieved human evidence.

Model-organism inference: systemic AGAT deficiency in mice was associated with protection from metabolic syndrome (a separate phenotype outside the core neurodevelopmental disorder), suggesting complex systemic metabolic consequences of creatine depletion. (ndika2012developmentalprogressand pages 1-2)

2.4 Gene–environment interactions

No direct gene–environment interaction evidence specific to AGAT deficiency was identified in the retrieved literature.

3. Phenotypes

3.1 Core clinical phenotype spectrum

Across the largest human cohort retrieved (n=16), the dominant presentation was neurodevelopmental impairment with frequent myopathy: - Intellectual disability/developmental delay: 15/16 patients. (stockleripsiroglu2015arginineglycineamidinotransferase(agat) pages 1-2) - Myopathy/proximal muscle weakness: 8/16 patients. (stockleripsiroglu2015arginineglycineamidinotransferase(agat) pages 1-2) - Language delay / severe speech-language disorder: commonly reported. (stockleripsiroglu2015arginineglycineamidinotransferase(agat) pages 1-2, pintilie2021ararebut pages 4-5) - Behavioral/psychiatric features (including autistic-like features): reported in multiple families/reviews. (pintilie2021ararebut pages 4-5, ndika2012developmentalprogressand pages 1-2) - Seizures: rare/variable; present in some reports. (stockleripsiroglu2015arginineglycineamidinotransferase(agat) pages 1-2, ndika2012developmentalprogressand pages 1-2)

3.2 Age of onset, severity, and progression

3.3 Laboratory/biochemical phenotypes (laboratory abnormalities)

3.4 Suggested HPO terms (non-exhaustive)

Based on retrieved clinical descriptions: - Developmental delay — HP:0001263 (stockleripsiroglu2015arginineglycineamidinotransferase(agat) pages 1-2) - Intellectual disability — HP:0001249 (stockleripsiroglu2015arginineglycineamidinotransferase(agat) pages 1-2) - Speech delay / severe speech impairment — HP:0000750 (speech delay) / HP:0002463 (aphasia may be too specific) (stockleripsiroglu2015arginineglycineamidinotransferase(agat) pages 1-2) - Hypotonia — HP:0001252 (ndika2012developmentalprogressand pages 1-2) - Proximal muscle weakness / myopathy — HP:0003701 (proximal muscle weakness) / HP:0003198 (myopathy) (stockleripsiroglu2015arginineglycineamidinotransferase(agat) pages 1-2) - Seizures — HP:0001250 (ndika2012developmentalprogressand pages 1-2) - Autistic-like behavior / behavioral abnormality — HP:0000729 (autistic behavior) / HP:0000708 (behavioral abnormality) (pintilie2021ararebut pages 4-5)

Note: HPO IDs are standard ontology suggestions; the supporting evidence for the phenotype presence is from the cited papers above.

4. Genetic/Molecular Information

4.1 Causal gene

4.2 Inheritance

4.3 Pathogenic variant spectrum and examples

Reported variant types include truncating/null variants, missense variants, and splice variants. (stockleripsiroglu2015arginineglycineamidinotransferase(agat) pages 5-7)

Examples explicitly mentioned in retrieved evidence: - c.484+1G>T (splice) in a long-term supplementation case series context. (ndika2012developmentalprogressand pages 1-2) - p.W149X (nonsense) reported in the Longo review excerpt and as a shared variant in an Italian family follow-up cohort (p.Trp149). (longo2011disordersofcreatine pages 2-3, battini2017fifteenyearfollowupof pages 2-4) - 1111_1112insA (frameshift insertion) in a two-patient report. (edvardson2010larginineglycineamidinotransferase(agat) pages 1-2) - R169X* (nonsense) in an adult-onset myopathy report. (verma2010arginineglycineamidinotransferasedeficiency pages 1-3)

4.4 Variant interpretation guidance (expert consensus; 2024)

The ClinGen CCDS VCEP created gene- and disease-specific ACMG/AMP specifications for GATM, explicitly integrating disease biomarkers (GAA/creatine in body fluids and brain MRS creatine) into phenotype evidence (PP4) via a points-based system. (goldstein2024clingenvariantcuration pages 8-9, goldstein2024clingenvariantcuration pages 13-18)

Key quantitative thresholds reported for GATM by the VCEP include: - Estimated prevalence used for calculations: 1 in 3,450,000 (goldstein2024clingenvariantcuration pages 4-6) - Allele frequency thresholds: BA1 >0.0005, BS1 >0.0001, PM2_supporting <0.000055. (goldstein2024clingenvariantcuration pages 13-18)

4.5 Modifier genes / epigenetics / chromosomal abnormalities

No modifier genes, epigenetic mechanisms, or chromosomal abnormalities specific to AGAT deficiency were identified in the retrieved evidence.

5. Environmental Information

No disease-specific environmental toxins, lifestyle contributors, or infectious triggers were identified in the retrieved evidence. AGAT deficiency is primarily a genetic enzymatic deficiency. (mulik2023creatinedeficiencydisorders pages 2-3, goldstein2024clingenvariantcuration pages 3-4)

6. Mechanism / Pathophysiology

6.1 Core biochemical pathway defect

AGAT catalyzes the first and rate-limiting step of creatine biosynthesis: - Arginine + glycine → guanidinoacetate (GAA) + ornithine. (edvardson2010larginineglycineamidinotransferase(agat) pages 1-2, verma2010arginineglycineamidinotransferasedeficiency pages 1-3)

Loss of AGAT activity causes: - Marked reduction of GAA production (low/undetectable GAA in urine/plasma). (stockleripsiroglu2015arginineglycineamidinotransferase(agat) pages 1-2) - Secondary creatine deficiency, including in brain, detectable as absent/markedly reduced creatine signal by 1H-MRS. (stockleripsiroglu2015arginineglycineamidinotransferase(agat) pages 2-3)

6.2 Causal chain (upstream → downstream)

  • Upstream trigger: biallelic loss-of-function variants in GATM → reduced/absent AGAT enzyme function. (goldstein2024clingenvariantcuration pages 3-4)
  • Metabolic consequence: low GAA and deficient creatine synthesis → inadequate creatine/phosphocreatine availability, particularly in energy-demanding tissues (brain, muscle). (mulik2023creatinedeficiencydisorders pages 2-3, stockleripsiroglu2015arginineglycineamidinotransferase(agat) pages 1-2)
  • Clinical consequence: neurodevelopmental impairment with major speech/language deficits and myopathy/proximal weakness; seizures variably. (stockleripsiroglu2015arginineglycineamidinotransferase(agat) pages 1-2)

6.3 Key biochemical abnormalities (diagnostic biomarkers)

6.4 Suggested GO and CL terms (mechanism-oriented suggestions)

  • GO:0006600 creatine biosynthetic process (general) (supported conceptually by creatine synthesis defect described in multiple sources). (mulik2023creatinedeficiencydisorders pages 2-3, edvardson2010larginineglycineamidinotransferase(agat) pages 1-2)
  • GO:0003848 arginine:glycine amidinotransferase activity (enzyme function) (edvardson2010larginineglycineamidinotransferase(agat) pages 1-2)
  • CL terms (likely impacted cell types):
  • Neurons (e.g., cortical neurons) and skeletal muscle myocytes as high-energy demand cell types implicated by clinical phenotype and MRS/myopathy findings. (stockleripsiroglu2015arginineglycineamidinotransferase(agat) pages 1-2)

7. Anatomical Structures Affected

7.1 Organ/system level

7.2 Suggested UBERON terms (examples)

  • Brain — UBERON:0000955 (stockleripsiroglu2015arginineglycineamidinotransferase(agat) pages 2-3)
  • Skeletal muscle tissue — UBERON:0001134 (stockleripsiroglu2015arginineglycineamidinotransferase(agat) pages 1-2)

7.3 Subcellular localization (suggested)

AGAT is encoded by mitochondrial glycine amidinotransferase (gene-level description in review literature), suggesting mitochondrial relevance in creatine biosynthesis and cellular energy buffering. (longo2011disordersofcreatine pages 2-3)

8. Temporal Development

8.1 Onset

Common onset is in infancy/early childhood with developmental delay and speech delay, though diagnosis may occur later and adult-onset myopathy has been described. (stockleripsiroglu2015arginineglycineamidinotransferase(agat) pages 1-2, verma2010arginineglycineamidinotransferasedeficiency pages 1-3, ndika2012developmentalprogressand pages 5-6)

8.2 Progression/course

9. Inheritance and Population

9.1 Epidemiology (rarity)

AGAT deficiency is consistently described as ultrarare, with <20–25 individuals reported in the literature in recent summaries. (mulik2023creatinedeficiencydisorders pages 2-3, goldstein2024clingenvariantcuration pages 1-3)

9.2 Prevalence / carrier frequency estimates

9.3 Penetrance/expressivity

ClinGen VCEP treated biallelic pathogenic variants in GATM as fully penetrant for purposes of allele-frequency calculations and variant interpretation (maximum genetic contribution and penetrance set to 100%). (goldstein2024clingenvariantcuration pages 4-6)

10. Diagnostics

10.1 Core diagnostic tests and biomarkers

Biochemical testing - Urine and plasma GAA and creatine measurements are central; low/undetectable GAA with low creatine supports AGAT deficiency. (mulik2023creatinedeficiencydisorders pages 2-3, stockleripsiroglu2015arginineglycineamidinotransferase(agat) pages 1-2)

Neuroimaging - 1H-MRS: absent/markedly decreased brain creatine peak is a hallmark; MRI can be normal. (stockleripsiroglu2015arginineglycineamidinotransferase(agat) pages 2-3, garg2024magneticresonancespectroscopy pages 2-4)

Genetic confirmation - GATM sequencing (single gene, panel, WES/WGS) to confirm biallelic pathogenic variants. (stockleripsiroglu2015arginineglycineamidinotransferase(agat) pages 7-8)

Functional confirmation - In uncertain genetic cases, AGAT enzyme activity in fibroblasts may help resolve interpretation. (mulik2023creatinedeficiencydisorders pages 2-3, goldstein2024clingenvariantcuration pages 13-18)

10.2 Real-world diagnostic implementation and delays (statistics)

A Swiss cross-sectional/systems study (2015–2023) on cerebral creatine deficiency disorders reported: - Diagnostic/therapeutic delay 3–32 months (mean 13.8 months) in their cohort. (kaufman2025diagnosticdelayin pages 1-2) - Total 4,967 guanidinoacetate and creatine measurements performed (urine+plasma) across two Swiss centers (2015–2023). (kaufman2025diagnosticdelayin pages 4-5) - Testing volume increased from 312 analyses (2015) to 883 (2023). (kaufman2025diagnosticdelayin pages 2-4) - Urine is described as “the preferred sample for CCDD detection” and “clearly the best matrix for the initial selective screening.” (kaufman2025diagnosticdelayin pages 1-2, kaufman2025diagnosticdelayin pages 6-8)

10.3 Differential diagnosis (high-level)

AGAT deficiency should be differentiated from other cerebral creatine deficiency disorders: - GAMT deficiency (elevated GAA rather than low) and SLC6A8 creatine transporter deficiency (different urine creatine/creatinine patterns; often poor response to creatine). (mulik2023creatinedeficiencydisorders pages 1-2, kaufman2025diagnosticdelayin pages 1-2)

10.4 Screening

Newborn screening feasibility and challenges - The 2015 cohort argues AGAT deficiency is “an ideal candidate for newborn screening” because early treatment can prevent adverse outcomes, but notes it is “difficult to devise a sensitive screening algorithm based on GAA quantitation alone,” proposing multianalyte DBS algorithms or enzyme assay approaches. (stockleripsiroglu2015arginineglycineamidinotransferase(agat) pages 7-8)

11. Outcome / Prognosis

11.1 Prognosis with treatment (long-term data)

A 15-year follow-up cohort (Italy; 4 patients) indicates: - Long-term oral creatine is generally safe and well tolerated; renal function was preserved with monitoring, though occasional kidney stones and other side effects occurred. (battini2017fifteenyearfollowupof pages 4-7) - Early treatment can prevent adverse developmental outcomes; later-treated patients often have persistent neurocognitive deficits, but adaptive functioning can improve. (battini2017fifteenyearfollowupof pages 1-2)

11.2 Prognostic factors

Age at treatment initiation is repeatedly highlighted as the dominant prognostic factor for neurocognitive outcomes. (mulik2023creatinedeficiencydisorders pages 2-3, stockleripsiroglu2015arginineglycineamidinotransferase(agat) pages 1-2)

12. Treatment

12.1 Standard-of-care pharmacotherapy

Creatine monohydrate supplementation is the main disease-specific therapy.

Dosing ranges reported across studies: - 100–800 mg/kg/day across cohorts and reviews. (stockleripsiroglu2015arginineglycineamidinotransferase(agat) pages 1-2, mulik2023creatinedeficiencydisorders pages 2-3) - A 2023 review states: “While all 3 disorders are currently treated with creatine supplementation,” and specifies for AGAT deficiency that oral creatine has been used and benefit depends on early initiation. (mulik2023creatinedeficiencydisorders pages 1-2)

Evidence for time-dependent neurocognitive benefit (review): - Cognitive restoration reported when treatment started <2 years, but not when started after age 10 in the 2023 review summary. (mulik2023creatinedeficiencydisorders pages 2-3)

Long-term treatment strategies / tapering (Italian follow-up cohort): - Symptomatic patients began at ~400 mg/kg/day, later reduced to 200–300 mg/kg/day, then 100 mg/kg/day guided by MRS and biochemical monitoring. (battini2017fifteenyearfollowupof pages 1-2)

12.2 Treatment outcomes

  • Creatine supplementation often increases cerebral creatine on MRS and improves myopathy; however, complete normalization of cerebral creatine is not universal even with very high doses. (stockleripsiroglu2015arginineglycineamidinotransferase(agat) pages 7-8)
  • In an MRS-focused clinical case report (44-month-old), pretreatment MRS had no definable creatine peak at 3.0 ppm and follow-up MRS at 5 months showed reappearance of the creatine peak after supplementation. (garg2024magneticresonancespectroscopy pages 2-4)

12.3 Adverse effects and monitoring

Reported adverse events/side effects with chronic creatine therapy include: - Weight gain, polyuria/polydipsia, transient diarrhea with dose increases, urinary creatine crystals, and kidney stones (at least one asymptomatic). (battini2017fifteenyearfollowupof pages 4-7, stockleripsiroglu2015arginineglycineamidinotransferase(agat) pages 7-8)

Monitoring strategies include serial urine/plasma creatine and GAA and periodic MRS (1H/31P) to track brain replenishment and guide dosing. (battini2017fifteenyearfollowupof pages 4-7)

12.4 Pregnancy management (real-world implementation)

A pregnancy case report (2020) describes a woman with AGAT deficiency requiring close monitoring due to increased creatine demand: - Abstract quote: “Biochemical monitoring of Cr in biological fluids of the mother revealed a decline of the Cr concentrations… requiring prompt correction of the Cr dose.” (Sep 2020). (alessandri2020increasedcreatinedemand pages 1-2) - The mother’s creatine dose was increased (e.g., to 3 g/day mid-pregnancy), and the infant had normal brain creatine and typical developmental milestones at one year. (alessandri2020increasedcreatinedemand pages 2-4, alessandri2020increasedcreatinedemand pages 1-2)

12.5 Suggested MAXO terms (treatment action ontology; suggestions)

13. Prevention

13.1 Primary/secondary prevention

No primary prevention exists for a Mendelian enzymatic deficiency, but secondary prevention via early detection and early creatine supplementation is repeatedly emphasized.

Early treatment prevention concept: - A 2023 review notes the disorders are treatable with creatine, and early treatment in AGAT deficiency can prevent adverse outcomes. (mulik2023creatinedeficiencydisorders pages 2-3) - A 2015 cohort states: “Early treatment seems to prevent adverse developmental outcomes.” (stockleripsiroglu2015arginineglycineamidinotransferase(agat) pages 7-8)

13.2 Newborn screening implementation

  • Early Check expanded newborn screening program includes AGAT deficiency on its screening panel and operationalizes confirmatory testing and genetic counseling after positive screens (observational cohort; estimated enrollment 30,000 newborns). (NCT03655223 chunk 2)

14. Other Species / Natural Disease

No naturally occurring veterinary cases were retrievable in the accessible full texts for this run (a relevant 2026 dog paper was listed as unobtainable by the search tool). Therefore, no curated cross-species natural disease entry can be provided from the current evidence set.

15. Model Organisms

15.1 Mouse model evidence

An AGAT-deficient mouse model has been used to study systemic creatine depletion and metabolic consequences; one study reports that AGAT deficiency protects from metabolic syndrome (model-organism phenotype not directly equivalent to the human neurodevelopmental disorder but informative for systemic pathway biology). (ndika2012developmentalprogressand pages 1-2)

Key abstract quotes (supporting major claims)

  1. Creatine deficiency disorders review (Mar 2023):

  2. “Biallelic pathogenic variants in GATM result in l-arginine:glycine amidinotransferase deficiency.” (mulik2023creatinedeficiencydisorders pages 2-3)

  3. Pregnancy in AGAT deficiency (Sep 2020):

  4. “Biochemical monitoring of Cr in biological fluids of the mother revealed a decline of the Cr concentrations… requiring prompt correction of the Cr dose.” (alessandri2020increasedcreatinedemand pages 1-2)

  5. Long-term Italian follow-up (Feb 2017):

  6. “Consecutive MRS examinations have confirmed that Cr depletion in AGAT-d patients is reversible under Cr supplementation.” (ndika2012developmentalprogressand pages 1-2)

Summary artifact

The following table provides a compact disease knowledge-base-ready summary (identifiers, biomarkers, phenotypes, diagnostics, dosing, outcomes, screening):

Table (click to expand)
Domain Key facts Key sources (citation ids) URLs/publication years when available
Disease/identifiers AGAT deficiency is a GATM-related cerebral creatine deficiency disorder, inherited in an autosomal recessive manner; reported as ultrarare with fewer than 20-25 patients/individuals described in the literature. OMIM identifiers reported in gathered evidence include AGAT deficiency OMIM #612718 and GATM gene OMIM #602360. MONDO association evidence supports MONDO:0012996 for AGAT deficiency. (mulik2023creatinedeficiencydisorders pages 2-3, mulik2023creatinedeficiencydisorders pages 1-2, longo2011disordersofcreatine pages 2-3) Mulik 2023: https://doi.org/10.5152/turkarchpediatr.2023.23022; Longo 2011: https://doi.org/10.1002/ajmg.c.30292; Open Targets evidence includes MONDO_0012996
Gene/mechanism GATM encodes AGAT, the first/rate-limiting enzyme of creatine biosynthesis, catalyzing arginine + glycine to guanidinoacetate (GAA) and ornithine. Disease mechanism is loss of function; ClinGen CCDS VCEP applies PVS1 to GATM and considers AGAT deficiency a fully penetrant autosomal recessive creatine synthesis disorder. (edvardson2010larginineglycineamidinotransferase(agat) pages 1-2, goldstein2024clingenvariantcuration pages 3-4, goldstein2024clingenvariantcuration pages 4-6) Edvardson 2010: https://doi.org/10.1016/j.ymgme.2010.06.021; Goldstein 2024: https://doi.org/10.1016/j.ymgme.2024.108362
Biochemical signature Hallmark profile: very low/undetectable GAA in urine and plasma, low or low-normal creatine/creatinine in urine, plasma, and sometimes CSF, with absent or markedly decreased brain creatine peak on 1H-MRS. Pretreatment cerebral creatine is markedly reduced or absent in essentially all studied patients. (mulik2023creatinedeficiencydisorders pages 2-3, stockleripsiroglu2015arginineglycineamidinotransferase(agat) pages 1-2, stockleripsiroglu2015arginineglycineamidinotransferase(agat) pages 5-7, stockleripsiroglu2015arginineglycineamidinotransferase(agat) pages 2-3) Mulik 2023: https://doi.org/10.5152/turkarchpediatr.2023.23022; Stockler-Ipsiroglu 2015: https://doi.org/10.1016/j.ymgme.2015.10.003
Core phenotypes Most common manifestations are developmental delay/intellectual disability and severe speech/language delay; behavioral problems/autistic-like features are frequent. Myopathy/proximal muscle weakness occurs in about half of reported patients or 8/16 in the largest series; hypotonia, failure to thrive/low weight, and rare seizures have also been reported. (stockleripsiroglu2015arginineglycineamidinotransferase(agat) pages 1-2, pintilie2021ararebut pages 4-5, verma2010arginineglycineamidinotransferasedeficiency pages 1-3, ndika2012developmentalprogressand pages 5-6) Stockler-Ipsiroglu 2015: https://doi.org/10.1016/j.ymgme.2015.10.003; Pintilie 2021: https://doi.org/10.37897/rjp.2021.3.4; Verma 2010: https://doi.org/10.1212/wnl.0b013e3181e7cabd; Ndika 2012: https://doi.org/10.1016/j.ymgme.2012.01.017
Onset/natural history Age at diagnosis reported from 3 weeks to 23 years. Early infancy/childhood presentations predominate, but adult-onset or later-recognized myopathy has been described. Untreated disease can lead to persistent cognitive/language impairment; early-treated infants can remain asymptomatic or achieve normal neurodevelopment. (stockleripsiroglu2015arginineglycineamidinotransferase(agat) pages 1-2, verma2010arginineglycineamidinotransferasedeficiency pages 1-3, ndika2012developmentalprogressand pages 5-6, battini2017fifteenyearfollowupof pages 1-2) Stockler-Ipsiroglu 2015: https://doi.org/10.1016/j.ymgme.2015.10.003; Verma 2010: https://doi.org/10.1212/wnl.0b013e3181e7cabd; Ndika 2012: https://doi.org/10.1016/j.ymgme.2012.01.017; Battini 2017: https://doi.org/10.1186/s13023-017-0577-5
Diagnostics Recommended workup includes urine and plasma GAA/creatine testing, brain 1H-MRS to document absent or reduced creatine peak, and confirmatory GATM sequencing; WES/WGS are alternatives. Functional confirmation can include AGAT enzyme activity in fibroblasts when variants are uncertain. ClinGen 2024 formalized phenotype/biomarker-based PP4 scoring using low GAA, low creatine, MRS findings, and enzyme activity. (mulik2023creatinedeficiencydisorders pages 2-3, stockleripsiroglu2015arginineglycineamidinotransferase(agat) pages 1-2, stockleripsiroglu2015arginineglycineamidinotransferase(agat) pages 7-8, goldstein2024clingenvariantcuration pages 8-9, goldstein2024clingenvariantcuration pages 13-18) Mulik 2023: https://doi.org/10.5152/turkarchpediatr.2023.23022; Stockler-Ipsiroglu 2015: https://doi.org/10.1016/j.ymgme.2015.10.003; Goldstein 2024: https://doi.org/10.1016/j.ymgme.2024.108362
MRS implementation Brain MRI may be normal, but MRS is highly informative: absent/undefinable creatine peak at ~3.0 ppm is a characteristic finding, and follow-up MRS can document reappearance of the peak after treatment. (garg2024magneticresonancespectroscopy pages 4-5, garg2024magneticresonancespectroscopy pages 2-4, garg2024magneticresonancespectroscopy pages 1-2) Garg 2024: https://doi.org/10.25259/crcr_92_2024
Treatment Main disease-specific therapy is oral creatine monohydrate supplementation. Dosing reported across studies ranges from 100-800 mg/kg/day; common long-term regimens include ~400 mg/kg/day initially with later taper to 200-100 mg/kg/day based on MRS/biochemical monitoring. Adult case reports also used 5 g/day with later escalation to weight-based dosing. (mulik2023creatinedeficiencydisorders pages 2-3, stockleripsiroglu2015arginineglycineamidinotransferase(agat) pages 1-2, stockleripsiroglu2015arginineglycineamidinotransferase(agat) pages 3-4, battini2017fifteenyearfollowupof pages 1-2, battini2017fifteenyearfollowupof pages 7-8) Mulik 2023: https://doi.org/10.5152/turkarchpediatr.2023.23022; Stockler-Ipsiroglu 2015: https://doi.org/10.1016/j.ymgme.2015.10.003; Battini 2017: https://doi.org/10.1186/s13023-017-0577-5
Treatment outcomes Creatine supplementation significantly improves or normalizes muscle function in most patients and increases cerebral creatine on MRS, but complete normalization is not universal even at high doses. Developmental/cognitive outcomes are strongly time-dependent: treatment begun in infancy (<2 years in review evidence; as early as 4-16 months in case series) can prevent adverse neurodevelopmental outcomes, whereas treatment started after ~10 years yields limited cognitive recovery. (mulik2023creatinedeficiencydisorders pages 2-3, stockleripsiroglu2015arginineglycineamidinotransferase(agat) pages 1-2, stockleripsiroglu2015arginineglycineamidinotransferase(agat) pages 7-8, battini2017fifteenyearfollowupof pages 1-2, battini2017fifteenyearfollowupof pages 4-7) Mulik 2023: https://doi.org/10.5152/turkarchpediatr.2023.23022; Stockler-Ipsiroglu 2015: https://doi.org/10.1016/j.ymgme.2015.10.003; Battini 2017: https://doi.org/10.1186/s13023-017-0577-5
Monitoring/adverse effects Monitoring strategies include serial plasma/urine creatine and GAA, neuropsychological assessment, and repeat brain MRS. Reported adverse effects are generally mild but include weight gain, polyuria/polydipsia, transient diarrhea with dose increases, urinary creatine crystals, and occasional kidney stones; renal function was generally preserved in long-term follow-up. (battini2017fifteenyearfollowupof pages 1-2, battini2017fifteenyearfollowupof pages 4-7, battini2017fifteenyearfollowupof pages 7-8) Battini 2017: https://doi.org/10.1186/s13023-017-0577-5
Epidemiology/screening implementation AGAT deficiency is an extreme ultrarare disorder; ClinGen used an estimated prevalence of ~1 in 3,450,000 for GATM-related disease in variant-classification threshold setting. Newborn screening is considered attractive because early treatment can prevent disease, but AGAT is harder to detect than GAMT using GAA alone; proposed approaches include multianalyte dried-blood-spot algorithms or enzyme assays. Early Check (NCT03655223) explicitly includes AGAT deficiency in an expanded newborn screening program, while BioCDS (NCT02934854) aimed to develop DBS mass-spectrometry biomarkers but was withdrawn with enrollment 0. (goldstein2024clingenvariantcuration pages 4-6, stockleripsiroglu2015arginineglycineamidinotransferase(agat) pages 7-8, NCT03655223 chunk 2, NCT02934854 chunk 1) Goldstein 2024: https://doi.org/10.1016/j.ymgme.2024.108362; Stockler-Ipsiroglu 2015: https://doi.org/10.1016/j.ymgme.2015.10.003; NCT03655223: https://clinicaltrials.gov/study/NCT03655223 (2018-ongoing); NCT02934854: https://clinicaltrials.gov/study/NCT02934854 (2018, withdrawn)

Table: This table condenses the most actionable disease-level facts for GATM-related AGAT deficiency, including identifiers, biochemical hallmarks, clinical presentation, diagnostics, and treatment evidence with dosing ranges. It is useful as a quick-reference artifact for a disease knowledge base entry.

Clinical trials / real-world studies relevant to AGAT deficiency

  1. Early Check: Expanded Screening in Newborns (ClinicalTrials.gov NCT03655223, posted 2018; observational; estimated enrollment 30,000)

  2. Explicitly lists Agat Deficiency on its screening panel and provides confirmatory testing and genetic counseling workflow. URL: https://clinicaltrials.gov/study/NCT03655223 (NCT03655223 chunk 2)

  3. Biomarker for Creatine Deficiency Syndromes (BioCDS) (ClinicalTrials.gov NCT02934854, posted 2018; observational; withdrawn, enrollment 0)

  4. Proposed DBS LC/MRM-MS biomarker discovery/validation with GATM sequencing; withdrawn due to “Transition into BioMetabol.” URL: https://clinicaltrials.gov/study/NCT02934854 (NCT02934854 chunk 1)

Important limitations of this report (data not retrieved in-tool)

  • Orphanet/MeSH/ICD codes were not retrieved via the available full texts and would require targeted database queries.
  • Variant-level allele frequencies in gnomAD and comprehensive ClinVar variant lists are not included beyond the ClinGen thresholds and exemplar variants available in the retrieved excerpts.
  • Many phenotype frequencies beyond IDD (15/16) and myopathy (8/16) were not extractable from the provided excerpts and would require full-table extraction from primary cohorts.

References

  1. (mulik2023creatinedeficiencydisorders pages 2-3): Crystal Mulik and Saadet Mercimek-Andrews. Creatine deficiency disorders: phenotypes, genotypes, diagnosis, and treatment outcomes. Turkish Archives of Pediatrics, 58:129-135, Mar 2023. URL: https://doi.org/10.5152/turkarchpediatr.2023.23022, doi:10.5152/turkarchpediatr.2023.23022. This article has 13 citations.

  2. (longo2011disordersofcreatine pages 2-3): Nicola Longo, Orly Ardon, Rena Vanzo, Elizabeth Schwartz, and Marzia Pasquali. Disorders of creatine transport and metabolism. American Journal of Medical Genetics Part C: Seminars in Medical Genetics, 157:72-78, Feb 2011. URL: https://doi.org/10.1002/ajmg.c.30292, doi:10.1002/ajmg.c.30292. This article has 135 citations.

  3. (goldstein2024clingenvariantcuration pages 3-4): Jennifer Goldstein, Amanda Thomas-Wilson, Emily Groopman, Vimla Aggarwal, Simona Bianconi, Raquel Fernandez, Kim Hart, Nicola Longo, Nicole Liang, Daniel Reich, Heidi Wallis, Meredith Weaver, Sarah Young, and Saadet Mercimek-Andrews. Clingen variant curation expert panel recommendations for classification of variants in gamt, gatm and slc6a8 for cerebral creatine deficiency syndromes. Molecular Genetics and Metabolism, 142:108362, May 2024. URL: https://doi.org/10.1016/j.ymgme.2024.108362, doi:10.1016/j.ymgme.2024.108362. This article has 12 citations and is from a peer-reviewed journal.

  4. (kaufman2025diagnosticdelayin pages 1-2): Christina Kaufman, Anaïs D’Andrea, Annette Hackenberg, Martin Poms, Olivier Braissant, and Johannes Häberle. Diagnostic delay in cerebral creatine deficiency disorders: lessons learned from a cross-sectional single center study, and guanidinoacetate and creatine measurements in switzerland between 2015 and 2023. Molecular and Cellular Pediatrics, Jan 2025. URL: https://doi.org/10.1186/s40348-024-00188-4, doi:10.1186/s40348-024-00188-4. This article has 2 citations.

  5. (garg2024magneticresonancespectroscopy pages 2-4): Ankita Garg, Rajiv Gupta, Jayesh Ashok Kumar Modi, and Debolina Kabiraj. Magnetic resonance spectroscopy as a diagnostic tool in cerebral creatine deficiency syndrome 3. Case Reports in Clinical Radiology, 0:1-5, Dec 2024. URL: https://doi.org/10.25259/crcr_92_2024, doi:10.25259/crcr_92_2024. This article has 0 citations.

  6. (edvardson2010larginineglycineamidinotransferase(agat) pages 1-2): Simon Edvardson, Stanley H. Korman, Amir Livne, Avraham Shaag, Ann Saada, Ruppen Nalbandian, Hyla Allouche-Arnon, J. Moshe Gomori, and Rachel Katz-Brull. L-arginine:glycine amidinotransferase (agat) deficiency: clinical presentation and response to treatment in two patients with a novel mutation. Molecular Genetics and Metabolism, 101:228-232, Oct 2010. URL: https://doi.org/10.1016/j.ymgme.2010.06.021, doi:10.1016/j.ymgme.2010.06.021. This article has 72 citations and is from a peer-reviewed journal.

  7. (stockleripsiroglu2015arginineglycineamidinotransferase(agat) pages 1-2): Sylvia Stockler-Ipsiroglu, Delia Apatean, Roberta Battini, Suzanne DeBrosse, Kimberley Dessoffy, Simon Edvardson, Florian Eichler, Katherine Johnston, David M. Koeller, Sonia Nouioua, Meriem Tazir, Ashok Verma, Monica D. Dowling, Klaas J. Wierenga, Andrea M. Wierenga, Victor Zhang, and Lee-Jun C. Wong. Arginine:glycine amidinotransferase (agat) deficiency: clinical features and long term outcomes in 16 patients diagnosed worldwide. Molecular Genetics and Metabolism, 116:252-259, Dec 2015. URL: https://doi.org/10.1016/j.ymgme.2015.10.003, doi:10.1016/j.ymgme.2015.10.003. This article has 82 citations and is from a peer-reviewed journal.

  8. (ndika2012developmentalprogressand pages 1-2): Joseph D.T. Ndika, Kathreen Johnston, James A. Barkovich, Michael D. Wirt, Patricia O'Neill, Ofir T. Betsalel, Cornelis Jakobs, and Gajja S. Salomons. Developmental progress and creatine restoration upon long-term creatine supplementation of a patient with arginine:glycine amidinotransferase deficiency. Molecular Genetics and Metabolism, 106:48-54, May 2012. URL: https://doi.org/10.1016/j.ymgme.2012.01.017, doi:10.1016/j.ymgme.2012.01.017. This article has 48 citations and is from a peer-reviewed journal.

  9. (verma2010arginineglycineamidinotransferasedeficiency pages 1-3): Ashok Verma. Arginine:glycine amidinotransferase deficiency: a treatable metabolic encephalomyopathy. Neurology, 75:186-188, Jul 2010. URL: https://doi.org/10.1212/wnl.0b013e3181e7cabd, doi:10.1212/wnl.0b013e3181e7cabd. This article has 24 citations and is from a highest quality peer-reviewed journal.

  10. (pintilie2021ararebut pages 4-5): Sebastian Romeo Pintilie, Adriana Fodor, Marius Bembea, Codruța Diana Petchesi, Simona Grad, Laura Damian, and Romana Vulturar. A rare but treatable inborn error of metabolism: arginine glycine amidinotransferase (agat) deficiency. Romanian Journal of Pediatrics, 70:186-191, Sep 2021. URL: https://doi.org/10.37897/rjp.2021.3.4, doi:10.37897/rjp.2021.3.4. This article has 0 citations.

  11. (ndika2012developmentalprogressand pages 5-6): Joseph D.T. Ndika, Kathreen Johnston, James A. Barkovich, Michael D. Wirt, Patricia O'Neill, Ofir T. Betsalel, Cornelis Jakobs, and Gajja S. Salomons. Developmental progress and creatine restoration upon long-term creatine supplementation of a patient with arginine:glycine amidinotransferase deficiency. Molecular Genetics and Metabolism, 106:48-54, May 2012. URL: https://doi.org/10.1016/j.ymgme.2012.01.017, doi:10.1016/j.ymgme.2012.01.017. This article has 48 citations and is from a peer-reviewed journal.

  12. (stockleripsiroglu2015arginineglycineamidinotransferase(agat) pages 2-3): Sylvia Stockler-Ipsiroglu, Delia Apatean, Roberta Battini, Suzanne DeBrosse, Kimberley Dessoffy, Simon Edvardson, Florian Eichler, Katherine Johnston, David M. Koeller, Sonia Nouioua, Meriem Tazir, Ashok Verma, Monica D. Dowling, Klaas J. Wierenga, Andrea M. Wierenga, Victor Zhang, and Lee-Jun C. Wong. Arginine:glycine amidinotransferase (agat) deficiency: clinical features and long term outcomes in 16 patients diagnosed worldwide. Molecular Genetics and Metabolism, 116:252-259, Dec 2015. URL: https://doi.org/10.1016/j.ymgme.2015.10.003, doi:10.1016/j.ymgme.2015.10.003. This article has 82 citations and is from a peer-reviewed journal.

  13. (stockleripsiroglu2015arginineglycineamidinotransferase(agat) pages 5-7): Sylvia Stockler-Ipsiroglu, Delia Apatean, Roberta Battini, Suzanne DeBrosse, Kimberley Dessoffy, Simon Edvardson, Florian Eichler, Katherine Johnston, David M. Koeller, Sonia Nouioua, Meriem Tazir, Ashok Verma, Monica D. Dowling, Klaas J. Wierenga, Andrea M. Wierenga, Victor Zhang, and Lee-Jun C. Wong. Arginine:glycine amidinotransferase (agat) deficiency: clinical features and long term outcomes in 16 patients diagnosed worldwide. Molecular Genetics and Metabolism, 116:252-259, Dec 2015. URL: https://doi.org/10.1016/j.ymgme.2015.10.003, doi:10.1016/j.ymgme.2015.10.003. This article has 82 citations and is from a peer-reviewed journal.

  14. (battini2017fifteenyearfollowupof pages 2-4): Roberta Battini, M. Grazia Alessandrì, Claudia Casalini, Manuela Casarano, Michela Tosetti, and Giovanni Cioni. Fifteen-year follow-up of italian families affected by arginine glycine amidinotransferase deficiency. Orphanet Journal of Rare Diseases, Feb 2017. URL: https://doi.org/10.1186/s13023-017-0577-5, doi:10.1186/s13023-017-0577-5. This article has 22 citations and is from a peer-reviewed journal.

  15. (goldstein2024clingenvariantcuration pages 8-9): Jennifer Goldstein, Amanda Thomas-Wilson, Emily Groopman, Vimla Aggarwal, Simona Bianconi, Raquel Fernandez, Kim Hart, Nicola Longo, Nicole Liang, Daniel Reich, Heidi Wallis, Meredith Weaver, Sarah Young, and Saadet Mercimek-Andrews. Clingen variant curation expert panel recommendations for classification of variants in gamt, gatm and slc6a8 for cerebral creatine deficiency syndromes. Molecular Genetics and Metabolism, 142:108362, May 2024. URL: https://doi.org/10.1016/j.ymgme.2024.108362, doi:10.1016/j.ymgme.2024.108362. This article has 12 citations and is from a peer-reviewed journal.

  16. (goldstein2024clingenvariantcuration pages 13-18): Jennifer Goldstein, Amanda Thomas-Wilson, Emily Groopman, Vimla Aggarwal, Simona Bianconi, Raquel Fernandez, Kim Hart, Nicola Longo, Nicole Liang, Daniel Reich, Heidi Wallis, Meredith Weaver, Sarah Young, and Saadet Mercimek-Andrews. Clingen variant curation expert panel recommendations for classification of variants in gamt, gatm and slc6a8 for cerebral creatine deficiency syndromes. Molecular Genetics and Metabolism, 142:108362, May 2024. URL: https://doi.org/10.1016/j.ymgme.2024.108362, doi:10.1016/j.ymgme.2024.108362. This article has 12 citations and is from a peer-reviewed journal.

  17. (goldstein2024clingenvariantcuration pages 4-6): Jennifer Goldstein, Amanda Thomas-Wilson, Emily Groopman, Vimla Aggarwal, Simona Bianconi, Raquel Fernandez, Kim Hart, Nicola Longo, Nicole Liang, Daniel Reich, Heidi Wallis, Meredith Weaver, Sarah Young, and Saadet Mercimek-Andrews. Clingen variant curation expert panel recommendations for classification of variants in gamt, gatm and slc6a8 for cerebral creatine deficiency syndromes. Molecular Genetics and Metabolism, 142:108362, May 2024. URL: https://doi.org/10.1016/j.ymgme.2024.108362, doi:10.1016/j.ymgme.2024.108362. This article has 12 citations and is from a peer-reviewed journal.

  18. (battini2017fifteenyearfollowupof pages 7-8): Roberta Battini, M. Grazia Alessandrì, Claudia Casalini, Manuela Casarano, Michela Tosetti, and Giovanni Cioni. Fifteen-year follow-up of italian families affected by arginine glycine amidinotransferase deficiency. Orphanet Journal of Rare Diseases, Feb 2017. URL: https://doi.org/10.1186/s13023-017-0577-5, doi:10.1186/s13023-017-0577-5. This article has 22 citations and is from a peer-reviewed journal.

  19. (battini2017fifteenyearfollowupof pages 4-7): Roberta Battini, M. Grazia Alessandrì, Claudia Casalini, Manuela Casarano, Michela Tosetti, and Giovanni Cioni. Fifteen-year follow-up of italian families affected by arginine glycine amidinotransferase deficiency. Orphanet Journal of Rare Diseases, Feb 2017. URL: https://doi.org/10.1186/s13023-017-0577-5, doi:10.1186/s13023-017-0577-5. This article has 22 citations and is from a peer-reviewed journal.

  20. (goldstein2024clingenvariantcuration pages 1-3): Jennifer Goldstein, Amanda Thomas-Wilson, Emily Groopman, Vimla Aggarwal, Simona Bianconi, Raquel Fernandez, Kim Hart, Nicola Longo, Nicole Liang, Daniel Reich, Heidi Wallis, Meredith Weaver, Sarah Young, and Saadet Mercimek-Andrews. Clingen variant curation expert panel recommendations for classification of variants in gamt, gatm and slc6a8 for cerebral creatine deficiency syndromes. Molecular Genetics and Metabolism, 142:108362, May 2024. URL: https://doi.org/10.1016/j.ymgme.2024.108362, doi:10.1016/j.ymgme.2024.108362. This article has 12 citations and is from a peer-reviewed journal.

  21. (stockleripsiroglu2015arginineglycineamidinotransferase(agat) pages 7-8): Sylvia Stockler-Ipsiroglu, Delia Apatean, Roberta Battini, Suzanne DeBrosse, Kimberley Dessoffy, Simon Edvardson, Florian Eichler, Katherine Johnston, David M. Koeller, Sonia Nouioua, Meriem Tazir, Ashok Verma, Monica D. Dowling, Klaas J. Wierenga, Andrea M. Wierenga, Victor Zhang, and Lee-Jun C. Wong. Arginine:glycine amidinotransferase (agat) deficiency: clinical features and long term outcomes in 16 patients diagnosed worldwide. Molecular Genetics and Metabolism, 116:252-259, Dec 2015. URL: https://doi.org/10.1016/j.ymgme.2015.10.003, doi:10.1016/j.ymgme.2015.10.003. This article has 82 citations and is from a peer-reviewed journal.

  22. (kaufman2025diagnosticdelayin pages 4-5): Christina Kaufman, Anaïs D’Andrea, Annette Hackenberg, Martin Poms, Olivier Braissant, and Johannes Häberle. Diagnostic delay in cerebral creatine deficiency disorders: lessons learned from a cross-sectional single center study, and guanidinoacetate and creatine measurements in switzerland between 2015 and 2023. Molecular and Cellular Pediatrics, Jan 2025. URL: https://doi.org/10.1186/s40348-024-00188-4, doi:10.1186/s40348-024-00188-4. This article has 2 citations.

  23. (kaufman2025diagnosticdelayin pages 2-4): Christina Kaufman, Anaïs D’Andrea, Annette Hackenberg, Martin Poms, Olivier Braissant, and Johannes Häberle. Diagnostic delay in cerebral creatine deficiency disorders: lessons learned from a cross-sectional single center study, and guanidinoacetate and creatine measurements in switzerland between 2015 and 2023. Molecular and Cellular Pediatrics, Jan 2025. URL: https://doi.org/10.1186/s40348-024-00188-4, doi:10.1186/s40348-024-00188-4. This article has 2 citations.

  24. (kaufman2025diagnosticdelayin pages 6-8): Christina Kaufman, Anaïs D’Andrea, Annette Hackenberg, Martin Poms, Olivier Braissant, and Johannes Häberle. Diagnostic delay in cerebral creatine deficiency disorders: lessons learned from a cross-sectional single center study, and guanidinoacetate and creatine measurements in switzerland between 2015 and 2023. Molecular and Cellular Pediatrics, Jan 2025. URL: https://doi.org/10.1186/s40348-024-00188-4, doi:10.1186/s40348-024-00188-4. This article has 2 citations.

  25. (mulik2023creatinedeficiencydisorders pages 1-2): Crystal Mulik and Saadet Mercimek-Andrews. Creatine deficiency disorders: phenotypes, genotypes, diagnosis, and treatment outcomes. Turkish Archives of Pediatrics, 58:129-135, Mar 2023. URL: https://doi.org/10.5152/turkarchpediatr.2023.23022, doi:10.5152/turkarchpediatr.2023.23022. This article has 13 citations.

  26. (battini2017fifteenyearfollowupof pages 1-2): Roberta Battini, M. Grazia Alessandrì, Claudia Casalini, Manuela Casarano, Michela Tosetti, and Giovanni Cioni. Fifteen-year follow-up of italian families affected by arginine glycine amidinotransferase deficiency. Orphanet Journal of Rare Diseases, Feb 2017. URL: https://doi.org/10.1186/s13023-017-0577-5, doi:10.1186/s13023-017-0577-5. This article has 22 citations and is from a peer-reviewed journal.

  27. (alessandri2020increasedcreatinedemand pages 1-2): Maria Grazia Alessandrì, Francesca Strigini, Giovanni Cioni, and Roberta Battini. Increased creatine demand during pregnancy in arginine: glycine amidino-transferase deficiency: a case report. BMC Pregnancy and Childbirth, Sep 2020. URL: https://doi.org/10.1186/s12884-020-03192-4, doi:10.1186/s12884-020-03192-4. This article has 15 citations and is from a peer-reviewed journal.

  28. (alessandri2020increasedcreatinedemand pages 2-4): Maria Grazia Alessandrì, Francesca Strigini, Giovanni Cioni, and Roberta Battini. Increased creatine demand during pregnancy in arginine: glycine amidino-transferase deficiency: a case report. BMC Pregnancy and Childbirth, Sep 2020. URL: https://doi.org/10.1186/s12884-020-03192-4, doi:10.1186/s12884-020-03192-4. This article has 15 citations and is from a peer-reviewed journal.

  29. (NCT03655223 chunk 2): Early Check: Expanded Screening in Newborns. RTI International. 2018. ClinicalTrials.gov Identifier: NCT03655223

  30. (garg2024magneticresonancespectroscopy pages 4-5): Ankita Garg, Rajiv Gupta, Jayesh Ashok Kumar Modi, and Debolina Kabiraj. Magnetic resonance spectroscopy as a diagnostic tool in cerebral creatine deficiency syndrome 3. Case Reports in Clinical Radiology, 0:1-5, Dec 2024. URL: https://doi.org/10.25259/crcr_92_2024, doi:10.25259/crcr_92_2024. This article has 0 citations.

  31. (garg2024magneticresonancespectroscopy pages 1-2): Ankita Garg, Rajiv Gupta, Jayesh Ashok Kumar Modi, and Debolina Kabiraj. Magnetic resonance spectroscopy as a diagnostic tool in cerebral creatine deficiency syndrome 3. Case Reports in Clinical Radiology, 0:1-5, Dec 2024. URL: https://doi.org/10.25259/crcr_92_2024, doi:10.25259/crcr_92_2024. This article has 0 citations.

  32. (stockleripsiroglu2015arginineglycineamidinotransferase(agat) pages 3-4): Sylvia Stockler-Ipsiroglu, Delia Apatean, Roberta Battini, Suzanne DeBrosse, Kimberley Dessoffy, Simon Edvardson, Florian Eichler, Katherine Johnston, David M. Koeller, Sonia Nouioua, Meriem Tazir, Ashok Verma, Monica D. Dowling, Klaas J. Wierenga, Andrea M. Wierenga, Victor Zhang, and Lee-Jun C. Wong. Arginine:glycine amidinotransferase (agat) deficiency: clinical features and long term outcomes in 16 patients diagnosed worldwide. Molecular Genetics and Metabolism, 116:252-259, Dec 2015. URL: https://doi.org/10.1016/j.ymgme.2015.10.003, doi:10.1016/j.ymgme.2015.10.003. This article has 82 citations and is from a peer-reviewed journal.

  33. (NCT02934854 chunk 1): Biomarker for Creatine Deficiency Syndromes (BioCDS). CENTOGENE GmbH Rostock. 2018. ClinicalTrials.gov Identifier: NCT02934854