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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
SLC46A1 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8653SLC46A181479 81479,81479 $990 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.

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing platform).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing platform).

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

For Sanger Sequencing click here.

Turnaround Time

3 weeks on average for standard orders or 2 weeks on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

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

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • McKenna Kyriss, PhD

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).

Genetics

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. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

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.

Gene

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

Disease

Name Inheritance OMIM ID
Folate Malabsorption, Hereditary AR 229050

Related Test

Name
Disorders of Folate Metabolism and Transport Panel

Citations

  • 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/Specimens

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.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

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

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.


Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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ORDER OPTIONS

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Note: acceptable specimen types are whole blood and DNA from whole blood only.
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