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IEMbase 0105: GATM-related arginine:glycine amidinotransferase deficiency

Scope

Field Value
IEMbase ID 105
Nosology 5.3.01.01
Gene GATM
External IDs OMIM:612718
Generated mapping MAPPED
Candidate DisMech targets AGAT_Deficiency.yaml
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents this as GATM-related arginine:glycine amidinotransferase deficiency, with alternate labels AGAT and cerebral creatine deficiency syndrome type 3. Treatability is marked yes.

The characteristic biochemical rows are markedly decreased brain creatine, low-to-normal urinary creatine/creatinine ratio, markedly decreased guanidinoacetic acid in CSF, plasma, and urine. Clinical rows are cerebral creatine deficiency and myopathy.

Treatment is creatine.

DisMech phenotype coverage

The generated mapping to AGAT_Deficiency.yaml is correct. The local entry covers biallelic GATM variants, reduced glycine amidinotransferase activity, reduced guanidinoacetate and creatine biosynthesis, cerebral creatine depletion, peripheral creatine depletion, and treatable myopathy.

Phenotype and biochemical coverage includes global developmental delay, cognitive impairment, speech-language delay, muscle weakness, myopathy, hypotonia, reduced brain creatine by MRS, reduced tissue AGAT activity, reduced circulating creatine, decreased urinary guanidinoacetic acid, decreased serum and urinary creatinine, and occasional seizures or behavioral findings. Treatment coverage includes creatine monohydrate supplementation.

Concordance and completeness

Judgement: correct mapping with high concordance.

IEMbase is more explicit about CSF, plasma, urine, and brain compartments and about the urinary creatine/creatinine ratio. DisMech is richer for molecular mechanism, peripheral myopathy mechanism, treatment timing, and broader developmental phenotype coverage.

Curation actions

  • Keep AGAT_Deficiency.yaml as the canonical target.
  • Consider adding a structured urinary creatine/creatinine ratio biomarker if biomarker normalization work continues.
  • No mapping correction needed.