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IEMbase 0104: GAMT-related guanidinoacetate methyltransferase deficiency

Scope

Field Value
IEMbase ID 104
Nosology 5.3.03.01
Gene GAMT
External IDs OMIM:612736
Generated mapping MAPPED
Candidate DisMech targets Guanidinoacetate_Methyltransferase_Deficiency.yaml
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents this as GAMT-related guanidinoacetate methyltransferase deficiency, with alternate label cerebral creatine deficiency syndrome type 2. Treatability is marked yes.

The characteristic biochemical rows are decreased creatine in CSF, plasma, and urine; markedly increased guanidinoacetic acid in CSF, plasma, and urine; and decreased creatinine in plasma and urine. The clinical rows are cerebral creatine deficiency and osteoporosis.

Treatments are arginine restriction and creatine plus ornithine.

DisMech phenotype coverage

The generated mapping to Guanidinoacetate_Methyltransferase_Deficiency.yaml is correct. The local entry covers biallelic GAMT variants, blocked methylation of guanidinoacetate to creatine, systemic and cerebral creatine depletion, neurotoxic guanidinoacetate accumulation, impaired neuronal energy homeostasis, and newborn-screening importance.

Phenotype and biochemical coverage includes global developmental delay, intellectual disability, speech-language delay, seizures, behavioral abnormalities, movement abnormalities, hypotonia, basal ganglia/globus pallidus abnormality, elevated guanidinoacetate, low creatine, low creatinine, and reduced brain creatine by MRS. Treatment coverage includes creatine supplementation, ornithine supplementation, and arginine restriction as substrate-reduction therapy.

Concordance and completeness

Judgement: correct mapping with high concordance.

IEMbase is more explicit about specimen compartments for creatine, guanidinoacetic acid, and creatinine. DisMech is richer for clinical phenotype surface, pathophysiology, treatment rationale, and evidence-backed newborn-screening context. Osteoporosis is an IEMbase-only clinical row in this comparison.

Curation actions

  • Keep Guanidinoacetate_Methyltransferase_Deficiency.yaml as the canonical target.
  • Consider osteoporosis as a phenotype review target before adding it to DisMech, because it is not part of the current local GAMT phenotype set.
  • No mapping correction needed.