Hereditary Folate Malabsorption via the SLC46A1 Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
8653 SLC46A1 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8653SLC46A181479 81479 $890 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

For Reflex to PGxome pricing click here.

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Turnaround Time

18 days on average for standard orders or 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.


Genetic Counselors


Clinical Features and Genetics

Clinical Features

Hereditary Folate Malabsorption (HFM) is a hereditary folate deficiency disorder that is characterized by defective intestinal folate absorption and impaired folate transport into the central nervous system. This results in low concentrations of folate in the serum and cerebrospinal fluid (Diop-Bove et al. 2014). In addition, some patients may be found to excrete formiminoglutamic acid (FIGLU) and/or orotic acid in the urine (Watkins and Rosenblatt 2014). Clinically, HFM is characterized by poor feeding and failure to thrive, severe megaloblastic anemia that may be accompanied by thrombocytopenia and/or leukopenia, diarrhea, mouth ulcers, hypoimmunoglobulinemia and other immunological dysfunction which may lead to infection with unusual organisms. The immunological deficiency may be severe enough to mimic severe combined immune deficiency (SCID), and undiagnosed infants may die early due to recurrent infections. Untreated patients that survive into early childhood may present with progressive neurological symptoms such as developmental delay, cognitive and motor impairment, seizures, ataxia and behavioral disorders (Diop-Bove et al. 2014; Watkins and Rosenblatt 2014). The onset of symptoms is usually at a few months of age as folate stores accumulated during gestation become depleted (Diop-Bove et al. 2014).

Early and correct diagnosis of HFM patients is essential for proper treatment. If treatment is initiated early in life, the signs and symptoms of the disorder may be prevented or reversed. If treatment is delayed, neurological defects may become permanent, and HFM may be fatal in untreated individuals (Zhao et al. 2007; Diop-Bove et al. 2014). Treatment generally consists of parenteral or high-dose oral administration of folinic acid, and is life-long for affected individuals (Diop-Bove et al. 2014).


Hereditary Folate Malabsorption is an autosomal recessive disorder, and the SLC46A1 gene is the only gene known to be associated with HFM (Qiu et al. 2006; Diop-Bove et al. 2014; Watkins and Rosenblatt 2014). This gene encodes the proton-coupled folate transporter protein, which is responsible for folate uptake in the intestines and across the blood-brain barrier (Diop-Bove et al. 2014). HFM is a rare disorder, with fewer than 20 pathogenic variants reported in the literature. Approximately half of the reported variants are missense. The remaining variants are mix of nonsense and splicing variants, as well as small deletions and insertions (Human Gene Mutation Database). The only common pathogenic variant reported thus far is a splice variant (c.1082-1G>A) which is common in individuals of Puerto Rican descent (Qiu et al. 2006; Mahadeo et al. 2011; Diop-Bove et al. 2014).

Clinical Sensitivity - Sequencing with CNV PGxome

At this time, the sensitivity of this test is difficult to estimate due to the low number of cases reported in the literature. However, analytical sensitivity of this test is expected to be high as, to date, all identified patients have been found to have two pathogenic variants detectable via direct sequencing (Zhao et al. 2007; Mahadeo et al. 2011; Shin et al. 2011; Diop-Bove et al. 2014).

Testing Strategy

This test provides full coverage of all coding exons of the SLC46A1 gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Indications for Test

Patients with clinical features of hereditary folate malabsorption are candidates for this test, particularly if they have been shown to have low serum and cerebrospinal fluid folate levels (Diop-Bove et al. 2014). Family members of patients known to have SLC46A1 variants are also good candidates, and we will sequence the SLC46A1 gene to determine carrier status.


Official Gene Symbol OMIM ID
SLC46A1 611672
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Folate Malabsorption, Hereditary AR 229050

Related Test

Disorders of Folate Metabolism and Transport Panel


  • Diop-Bove N. et al. 2014. Hereditary Folate Malabsorption. In: Pagon RA, Adam MP, Ardinger HH, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews(®), Seattle (WA): University of Washington, Seattle. PubMed ID: 20301716
  • Human Gene Mutation Database (Bio-base).
  • Mahadeo K.M. et al. 2011. The Journal of Pediatrics. 159: 623-7.e1. PubMed ID: 21489556
  • Qiu A. et al. 2006. Cell. 127: 917-28. PubMed ID: 17129779
  • Shin D.S. et al. 2011. Molecular Genetics and Metabolism. 103: 33-7. PubMed ID: 21333572
  • Watkins and Rosenblatt. 2014. Inherited Disorders of Folate and Cobalamin Transport and Metabolism. In: Valle D, Beaudet A.L., Vogelstein B, et al., editors. New York, NY: McGraw-Hill. OMMBID.
  • Zhao R. et al. 2007. Blood. 110: 1147-52. PubMed ID: 17446347


Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page

Specimen Types

Specimen Requirements and Shipping Details

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2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

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