IEMbase 0070: SLC46A1-related proton-coupled folate transporter deficiency
Scope
| Field | Value |
|---|---|
| IEMbase ID | 70 |
| Nosology | 21.8.01.01 |
| Gene | SLC46A1 |
| External IDs | OMIM:229050 |
| Generated mapping | UNMAPPED |
| Candidate DisMech targets | Best fuzzy candidate Primary_Carnitine_Deficiency.yaml |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents this as autosomal recessive SLC46A1-related proton-coupled folate transporter deficiency, with alternate labels hereditary folate malabsorption and HFM. Treatability is marked yes.
The characteristic biochemical signal includes abnormal 5-methyltetrahydrofolic acid in CSF, abnormal plasma folate, and abnormal plasma homocysteine. Other lab rows include urinary FIGLU, immunoglobulins, and plasma cobalamin.
Characteristic clinical rows include megaloblastic anemia, ataxia, neurologic deterioration, and recurrent infections. Additional rows include diarrhea, failure to thrive, heart failure, intellectual disability, movement disorder, peripheral neuropathy, pancytopenia, seizures, and stomatitis. The treatment row is levofolinic or folinic acid.
DisMech phenotype coverage
No valid local DisMech target was found for SLC46A1, proton-coupled folate transporter deficiency, or hereditary folate malabsorption.
The best fuzzy candidate, Primary_Carnitine_Deficiency.yaml, is a false
positive. That entry is an SLC22A5/OCTN2 carnitine-transport disorder with
systemic carnitine depletion, fatty-acid oxidation impairment, hypoketotic
hypoglycemia, hyperammonemia, hepatic encephalopathy, and cardiomyopathy. It
does not cover folate malabsorption, SLC46A1, CSF 5-MTHF deficiency,
megaloblastic anemia, or folinic-acid treatment.
Concordance and completeness
Judgement: true local gap.
This record is a treatable folate-transport disorder with combined intestinal malabsorption, immune/hematologic findings, and neurologic folate deficiency. It should not be mapped to a carnitine transporter disease despite superficial transporter/treatability similarity.
Curation actions
- Keep this IEMbase record unmapped for now.
- Add a future standalone hereditary folate malabsorption / SLC46A1 deficiency entry.
- If curated later, prioritize the folate transport block, CSF 5-MTHF/plasma folate/homocysteine biomarkers, megaloblastic anemia, immunodeficiency and infections, diarrhea/failure to thrive, neurologic deterioration, and folinic-acid treatment.