Clinical Guidance
SLC19A1 encodes the reduced folate carrier (RFC) protein that mediates transport of folates into mammalian cells. The clinical findings associated with SLC19A1-related folate transport deficiency (SLC19A1-FTD) depend on the degree of RFC functional loss associated with the pathogenic variants . With severe deficiency, signs may be present at or shortly after birth . With modest loss of function, clinical manifestations may be delayed and only emerge when dietary folate intake is insufficient . When the sole manifestations are hematologic, immunologic/infectious, and/or gastrointestinal, treatment with folate can completely reverse these signs and symptoms. Developmental and neurologic findings may improve with treatment depending on the extent and duration of impairment and adequacy of treatment (see Management, ). To date, five individuals from three families have been identified with biallelic pathogenic variants in SLC19A1 . In addition, two sibs died at an early age prior to diagnosis . The following description of the phenotypic features associated with this condition in untreated individuals is based on these reports. Table 2. SLC19A1-Related Folate Transport Deficiency: Frequency of Select Features in Untreated Individuals
Feature | Proportion of Persons w/Feature1 | Comment |
|---|
Megaloblastic anemia | 5/5 | — |
Recurrent infections | 4/5 | Most commonly respiratory |
Leukopenia /or thrombocytopenia | 4/5 | — |
Low immunoglobulin levels | 4/5 | — |
Mucositis (oral lesions) diarrhea | 4/5 | — |
Delayed myelination, cerebral/cerebellar calcifications on brain MRI | 3/3 | MRIs obtained in 3 persons only |
Developmental delay/ intellectual disability | 4/5 | — |
Seizures | 1/5 | Four of the five affected individuals had pathogenic variants predicted to cause a marked loss of RFC function. One affected individual, for whom the only manifestation was late-onset anemia, had a pathogenic variant predicted to cause only mild loss of protein function. Hematologic findings. |
Source: GeneReviews — "SLC19A1-Related Folate Transport Deficiency"
