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Refsum Disease via the PHYH 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
PHYH 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11581PHYH81479 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. If the Sanger option is selected, CNV detection may be ordered through Test #600.

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


  • Stela Berisha, PhD, FACMG

Clinical Features and Genetics

Clinical Features

Refsum disease, also known as adult Refsum disease (ARD), is usually late childhood onset. The first set of clinical symptoms includes anosmia, night blindness, and progressive retinitis pigmentosa. Other symptoms may occur in the following 10-15 years, including peripheral neuropathy, nerve deafness, cerebellar ataxia, ichthyosis, and skeletal dysplasia. Premature death is often due to cardiac arrhythmias. Unexplained remission has been observed in some patients. 90% of ARD cases are caused by PHYH mutations which lead to a peroxisomal single enzyme defect that results from deficiency of phytanoyl-CoA hydroxylase. The remaining 10% of all reported ARD patients are due to defects in PEX7, which is a peroxisome biogenesis disorder. For patients with PHYH mutations, the elevated phytanic acid in plasma and deficiency of phytanoyl-CoA hydroxylase enzyme activity are the diagnostic biochemical markers. Elevated pipecolic acid levels were found in about 20% of patients. Plasmalogen synthesis and VLCFA metabolism are normal. Elevated phytanic acid is thought to be toxic and also related to phenotypic variation. A phytanic acid restricted diet has been found to be effective treatment especially for children (Wanders et al. 2010; Jansen et al. 2004; Mihalik et al. 1997).


Refsum disease is inherited in an autosomal recessive manner. The PHYH gene encodes phytanoyl-CoA hydroxylase, which is a key enzyme for α-oxidation of branched-chain lipids. PHYH mutations have been found in more than 90% of individuals with Refsum disease. Reported PHYH mutations are loss-of-function variants including missense, nonsense, splicing site mutations, small deletion/insertions and a gross deletion. No clear phenotype-genotype correlation has been observed (Jansen et al. 2004).

Clinical Sensitivity - Sequencing with CNV PGxome

PHYH mutations are the major cause for Refsum disease and were found in more than 90% of patients (Wanders et al. 2010; Jansen et al. 2004).

Clinical sensitivity for del/dup testing is expected to be low. Only one gross deletion affecting PHYH exons 5-6 has been reported so far (Chahal et al. 1998).

Testing Strategy

This test provides full coverage of all coding exons of the PHYH 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 symptoms of Refsum disease. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in PHYH.


Official Gene Symbol OMIM ID
PHYH 602026
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Refsum Disease, Classic AR 266500


  • Chahal A, Khan M, Pai SG, Barbosa E, Singh I. 1998. Restoration of phytanic acid oxidation in Refsum disease fibroblasts from patients with mutations in the phytanoyl-CoA hydroxylase gene. FEBS Lett. 429: 119122. PubMed ID: 9657395
  • Jansen et al. 2004. PubMed ID: 14974078
  • Mihalik SJ, Morrell JC, Kim D, Sacksteder KA, Watkins PA, Gould SJ. 1997. Identification of PAHX, a Refsum disease gene. Nat. Genet. 17: 185189. PubMed ID: 9326939
  • Wanders RJ, Waterham HR, Leroy BP. 2010. Refsum Disease. 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: 20301527


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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View Ordering Instructions

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2) Select Additional Test Options

No Additional Test Options are available for this test.

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