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IEMbase 0071: FOLR1-related folate receptor alpha deficiency

Scope

Field Value
IEMbase ID 71
Nosology 21.8.02.01
Gene FOLR1
External IDs OMIM:613068
Generated mapping UNMAPPED
Candidate DisMech targets Best fuzzy candidate Pyruvate_Dehydrogenase_Deficiency.yaml#E1-alpha deficiency
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents this as autosomal recessive FOLR1-related folate receptor alpha deficiency, also labeled cerebral folate deficiency and CFD. Treatability is marked yes.

The characteristic biochemical signal includes abnormal CSF 5-methyltetrahydrofolic acid, plasma folate, and MRS choline and inositol rows. Characteristic clinical rows include ataxia, cerebral atrophy on MRI, dyskinesia, hypertonia, hypomyelination on MRI, seizures, and myoclonic-astatic seizures.

Additional clinical rows include autism spectrum disorder, aggressive behavior, cerebellar atrophy, chorea, developmental regression, abnormal EEG, gait disturbance, microcephaly, movement disorder, tonic-clonic seizures, increased tendon reflexes, and tremor. The treatment row is folinic acid.

DisMech phenotype coverage

No valid local DisMech target was found for FOLR1, folate receptor alpha deficiency, or primary cerebral folate deficiency.

The best fuzzy candidate, Pyruvate_Dehydrogenase_Deficiency.yaml#E1-alpha deficiency, is a false positive. PDH deficiency can include neurologic disease, seizures, and brain MRI abnormalities, but it is a pyruvate-to-acetyl-CoA oxidative decarboxylation disorder, not a folate receptor or CSF folate transport disorder.

The local Tetrahydrobiopterin_Deficiency.yaml entry mentions secondary cerebral folate deficiency in DHPR deficiency, but that is not FOLR1-related primary cerebral folate deficiency and should not be used as the mapping target.

Concordance and completeness

Judgement: true local gap.

This is a treatable folate-receptor disorder with a distinctive low-CSF 5-MTHF/folinic-acid axis and neurologic presentation. Current DisMech coverage only touches secondary cerebral folate issues in other disorders, not the primary FOLR1 disease.

Curation actions

  • Keep this IEMbase record unmapped for now.
  • Add a future standalone FOLR1 cerebral folate deficiency entry.
  • Preserve distinction from PDH deficiency and DHPR/BH4 deficiency, which can share neurologic or folate-related features but have different primary mechanisms.