Brown-Vialetto-Van Laere Syndrome 2 and Fazio-Londe Disease (Progressive Bulbar Palsy with or without Sensorineural Deafness) via the SLC52A2 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
9167 SLC52A2 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9167SLC52A281479 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. If the Sanger option is selected, CNV detection may be ordered through Test #600.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

For Reflex to PGxome pricing click here.

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

For Sanger Sequencing click here.

Targeted Testing

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

Turnaround Time

18 days on average

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Brown-Vialetto-van Laere syndrome (BVVLS) and Fazio-Londe disease are rare neurologic disorders caused by mutations in genes belonging to the RFVT/SLC52 riboflavin transporter gene family. BVVLS1 (OMIM 211530) and BVVLS2 (OMIM 614707) are rare autosomal recessive disorders with clinically similar findings of bulbar palsy, neurological deterioration, muscle weakness, respiratory insufficiency, and early death. Onset of symptoms has been reported in the first decade of life (Green et al. 2010). Sensorineural deafness was also found to be a common feature, but more often in patients with later onset. Fazio-Londe disease (OMIM 211500) is a progressive bulbar palsy with onset in childhood that presents with hypotonia and respiratory insufficiency due to diaphragmatic paralysis (Bosch et al. 2011). The Fazio-Londe disease patients described by Bosch et al. (2011) displayed plasma acylcarnitine and urine organic acid profiles suggestive of a mild form of the multiple acylCoA dehydrogenation defect (MADD). However, further biochemical testing revealed a profound flavin deficiency in spite of a normal dietary riboflavin intake. Brown-Vialetto-van Laere syndrome and Fazio-Londe disease are believed to represent variable presentations of a single disorder (Dipti et al. 2005). High-dose oral riboflavin supplementation therapy has recently been shown to decrease symptoms in patients with BVVLS (Foley et al. 2014). Brown-Vialetto-van Laere syndrome and Fazio-Londe disease are believed to represent variable presentations of a single disorder (Dipti et al. 2005).

Genetics

Brown-Vialetto-van-Laere syndrome-2 (BVVLS2) and Fazio-Londe Disease are inherited in an autosomal recessive manner. The SLC52A2 gene was identified as the cause of BVVLS2 (Johnson et al. 2012; Haack et al. 2012). The SLC52A2 gene (also known as RFVT2 and RFT3) is a member of the three gene riboflavin transporter gene family SLC52/RFVT (Yonezawa and Inui 2013). Functional studies have shown that mutations in SLC52A2 results in decreased uptake of riboflavin (Haack et al. 2012; Foley et al. 2014). A small number of patients worldwide have thus far been documented. SLC52A2 mutation types reported in patients include missense and nonsense.

Testing Strategy

This test provides full coverage of all coding exons of the SLC52A2 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).

Clinical Sensitivity - Sequencing with CNV PGxome

Brown-Vialetto-van Laere syndrome and Fazio-Londe disease are both rare disorders, and clinical sensitivity cannot yet be estimated. Analytical sensitivity should be high because all mutations thus far reported are expected to be detected by sequencing genomic DNA.

Indications for Test

Patients with clinical features consistent with Brown-Vialetto-van Laere syndrome or Fazio-Londe disease and demonstrated autosomal recessive inheritance. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in SLC52A2.

Gene

Official Gene Symbol OMIM ID
SLC52A2 607882
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Brown-Vialetto-Van Laere syndrome 2 AR 614707

Citations

  • Bosch AM, Abeling NGGM, IJlst L, Knoester H, Pol WL, Stroomer AEM, Wanders RJ, Visser G, Wijburg FA, Duran M, Waterham HR. 2010. Brown-Vialetto-Van Laere and Fazio Londe syndrome is associated with a riboflavin transporter defect mimicking mild MADD: a new inborn error of metabolism with potential treatment. Journal of Inherited Metabolic Disease 34: 159–164. PubMed ID: 21110228
  • Dipti S, Childs A-M, Livingston JH, Aggarwal AK, Miller M, Williams C, Crow YJ. 2005. Brown–Vialetto–Van Laere syndrome; variability in age at onset and disease progression highlighting the phenotypic overlap with Fazio-Londe disease. Brain and Development 27: 443–446. PubMed ID: 16122634
  • Foley AR, Menezes MP, Pandraud A, Gonzalez MA, Al-Odaib A, Abrams AJ, Sugano K, Yonezawa A, Manzur AY, Burns J, Hughes I, McCullagh BG, et al. 2014. Treatable childhood neuronopathy caused by mutations in riboflavin transporter RFVT2. Brain 137: 44–56. PubMed ID: 24253200
  • Green P, Wiseman M, Crow YJ, Houlden H, Riphagen S, Lin J-P, Raymond FL, Childs A-M, Sheridan E, Edwards S, Josifova DJ. 2010. Brown-Vialetto-Van Laere Syndrome, a Ponto-Bulbar Palsy with Deafness, Is Caused by Mutations in C20orf54. The American Journal of Human Genetics 86: 485–489. PubMed ID: 20206331
  • Haack TB, Makowski C, Yao Y, Graf E, Hempel M, Wieland T, Tauer U, Ahting U, Mayr JA, Freisinger P, Yoshimatsu H, Inui K, et al. 2012. Impaired riboflavin transport due to missense mutations in SLC52A2 causes Brown-Vialetto-Van Laere syndrome. J Inherit Metab Dis 35: 943–948. PubMed ID: 22864630
  • Johnson JO, Gibbs JR, Megarbane A, Urtizberea JA, Hernandez DG, Foley AR, Arepalli S, Pandraud A, Simon-Sanchez J, Clayton P, Reilly MM, Muntoni F, et al. 2012. Exome sequencing reveals riboflavin transporter mutations as a cause of motor neuron disease. Brain 135: 2875–2882. PubMed ID: 22740598
  • Yonezawa A, Inui K. 2013. Novel riboflavin transporter family RFVT/SLC52: identification, nomenclature, functional characterization and genetic diseases of RFVT/SLC52. Mol. Aspects Med. 34: 693–701. PubMed ID: 23506902

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.

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

loading Loading... ×

ORDER OPTIONS

View Ordering Instructions

1) Select Test Type


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.

Total Price: $
×
Copy Text to Clipboard
×