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Sepiapterin Reductase (SR) Deficiency via the SPR 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
SPR 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9043SPR81479 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.


Genetic Counselors


  • McKenna Kyriss, PhD

Clinical Features and Genetics

Clinical Features

Inborn errors of tetrahydrobiopterin (BH4) synthesis can result in disruption of phenylalanine homeostasis and dopamine and serotonin biosynthesis. These disorders are caused by pathogenic variants in genes encoding enzymes involved in biosynthesis or regeneration of BH4. The phenylalanine, tyrosine, and tryptophan hydroxylases all require BH4 as a cofactor, and lack of this cofactor often results in secondary hyperphenylalaninemia and depletion of the neurotransmitters dopamine and serotonin. Early detection and treatment can reduce or prevent neurologic symptoms (Blau et al. 2014).

Unlike other disorders of BH4 synthesis, patients with sepiapterin reductase (SR) deficiency do not present with hyperphenylalaninemia and are thus not detected by routine newborn screening. Alternative enzymes are able to compensate for the loss of SR activity in the peripheral tissues, but not in the brain, which explains why patients present with neurological symptoms, but no change in day-to-day phenylalanine homeostasis (Arrabal et al. 2011). Diagnosis of SR deficient patients is therefore based initially on clinical features, the most common of which are psychomotor and growth retardation, microcephaly, L-dopa responsive dystonia, spasticity, tremor, ataxia, behavioral anomalies, and oculogyric crises. Such symptoms often occur with marked diurnal fluctuations, with noticeable improvement after sleep (Bonafé et al. 2001; Steinberger et al. 2004; Friedman 2015).

Biochemically, SR deficient patients have low levels of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA), high levels of dihydrobiopterin (BH2), and slightly increased levels of neopterin and sepiapterin. If measured, SR activity in fibroblasts is decreased or absent, and patients will have normal levels of phenylalanine unless a phenylalanine loading test is performed, in which a greatly increased phenylalanine/tyrosine ratio is observed (Bonafé et al. 2001; Steinberger et al. 2004; Friedman 2015). Most SR deficient patients present in the early years of life, although diagnosis may be delayed if sepiapterin reductase (SR) deficiency is not considered early in testing (Arrabal et al. 2011). Once diagnosed, patients are typically treated with L-dopa or 5-hydroxytryptophan (5-HTP), potentially in combination with carbidopa. Treatment is often able to correct motor abnormalities, but cognitive difficulties may remain (Friedman 2015).


Sepiapterin reductase (SR) deficiency is inherited in an autosomal recessive manner. The SPR gene (chromosome 11q22.3, 3 exons) encodes the SR enzyme, which is involved in the de novo biosynthesis of tetrahydrobiopterin. More specifically, SR converts 6-pyruvoyl tetrahydropterin to tetrahydrobiopterin (Blau et al. 2014). To date, fewer than 20 pathogenic variants have been reported in the SR gene. These variants include a mix of missense, nonsense, splicing, and small deletions and insertions (Human Gene Mutation Database). Pathogenic variants are spread along the coding sequence with no obvious hot spots.

Clinical Sensitivity - Sequencing with CNV PGxome

Clinical sensitivity is difficult to estimate because only a small number of affected individuals have been reported. Analytical sensitivity should be high because all variants reported are detectable by direct sequencing.

Testing Strategy

This test provides full coverage of all coding exons of the SPR 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 and/or biochemical features suggestive of SR deficiency, especially patients with primary dystonias of unknown cause, are good candidates for this test. Additionally, family members of patients known to have SPR variants are good candidates. We will also sequence the SPR gene to determine carrier status.


Official Gene Symbol OMIM ID
SPR 182125
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Sepiapterin Reductase Deficiency AD, AR 612716

Related Tests

6-Pyruvoyltetrahydropterin Synthase (PTPS) Deficiency via the PTS Gene
Dihydropteridine Reductase (DHPR) Deficiency via the QDPR Gene


  • Arrabal L. et al. 2011. Neurogenetics. 12: 183-91.  PubMed ID: 21431957
  • Blau N.et al. 2014. Disorders of Tetrahydrobiopterin and Related Biogenic Amines. Online Metabolic & Molecular Bases of Inherited Disease, New York, NY: McGraw-Hill.
  • Bonafé L. et al. 2001. American Journal of Human Genetics. 69: 269-77. PubMed ID: 11443547
  • Friedman J. 2015. Sepiapterin Reductase Deficiency. 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: 26131547
  • Human Gene Mutation Database (Bio-base).
  • Steinberger D. et al. 2004. Neurogenetics. 5: 187-90.  PubMed ID: 15241655


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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