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IEMbase 0580: MTHFS-related 5,10-methenyltetrahydrofolate synthetase deficiency

Scope

Field Value
IEMbase ID 580
Nosology 21.8.07.01
Gene MTHFS
External IDs OMIM:604197
Generated mapping UNMAPPED; best candidate Carbamoyl_Phosphate_Synthetase_I_Deficiency.yaml
Candidate DisMech targets None exact
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents MTHFS-related 5,10-methenyltetrahydrofolate synthetase deficiency, with alternate label 5-formyltetrahydrofolate cycloligase. The record is autosomal recessive, classified under disorders of folate metabolism, has unknown treatability, and lists 5-methyltetrahydrofolate plus methylcobalamin.

The characteristic biochemical row is very decreased CSF 5-MTHF. Clinical rows include feeding difficulties, hyperthermia, intellectual disability, recurrent infections, and short stature.

DisMech phenotype coverage

Carbamoyl_Phosphate_Synthetase_I_Deficiency.yaml is a false-positive candidate. It models CPS1-related urea-cycle failure with hyperammonemia, low citrulline, and urea-cycle decompensation rather than MTHFS-related folate one-carbon metabolism.

The local knowledge base has related folate/remethylation and cerebral-folate context, but no exact MTHFS / 5-formyltetrahydrofolate cycloligase disease target was identified.

Concordance and completeness

Judgement: true local gap; reject CPS1 deficiency as an exact target.

The distinguishing IEMbase signal is a folate-metabolism disorder with low CSF 5-MTHF and folate-directed treatment rows. The generated CPS1 candidate shares only broad metabolic-disease neighborhood and does not match gene, pathway, biomarker, or treatment.

Curation actions

  • Create or identify an exact MTHFS deficiency target before import.
  • Reject Carbamoyl_Phosphate_Synthetase_I_Deficiency.yaml as an exact mapping.
  • Preserve the CSF 5-MTHF, folate/cobalamin treatment, recurrent-infection, hyperthermia, feeding, growth, and intellectual-disability prompts.