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IEMbase 0106: SLC6A8-related creatine transporter deficiency

Scope

Field Value
IEMbase ID 106
Nosology 5.3.04.01
Gene SLC6A8
External IDs OMIM:300352
Generated mapping CANDIDATE
Candidate DisMech targets Generated candidate AGAT_Deficiency.yaml is false; correct target is Creatine_Transporter_Deficiency.yaml
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents this as SLC6A8-related creatine transporter deficiency, with alternate labels cerebral creatine deficiency syndrome type 1 and X-linked creatine deficiency syndrome. Treatability is marked yes.

The characteristic biochemical row is increased urinary creatine/creatinine ratio. Clinical rows are constipation and low muscle mass.

Treatments are arginine, creatine, and glycine.

DisMech phenotype coverage

The generated CANDIDATE to AGAT_Deficiency.yaml is a false positive caused by shared cerebral creatine deficiency wording. The correct local target is Creatine_Transporter_Deficiency.yaml.

That entry covers X-linked SLC6A8-related creatine transporter deficiency, impaired CRTR-mediated creatine uptake, cerebral creatine depletion, impaired neuronal energy buffering, reduced brain creatine by MRS, global developmental delay, intellectual disability, seizures, hypotonia, speech-language delay, behavioral abnormalities, and occasional movement disorder. Its treatment section captures creatine precursor supplementation with creatine, arginine, and glycine, but explicitly notes that clinical improvement has not been proven because the transporter defect limits CNS benefit.

Concordance and completeness

Judgement: generated candidate is wrong, but a correct local standalone target exists.

IEMbase is more explicit about the urinary creatine/creatinine ratio and adds constipation and low muscle mass. DisMech is richer for the transporter-versus- biosynthesis distinction, X-linked inheritance, reduced brain creatine by MRS, neurodevelopmental phenotype surface, and treatment efficacy caveat.

Curation actions

  • Correct mapping to Creatine_Transporter_Deficiency.yaml.
  • Do not map to AGAT_Deficiency.yaml.
  • Consider adding urinary creatine/creatinine ratio as a structured biochemical readout and reviewing constipation/low muscle mass for future phenotype expansion.