Sign in →

Test ID: PDP Peroxisomal Disorder Panel by Next-Generation Sequencing

Useful For

Follow up of abnormal biochemical result, usually very long chain fatty acid test consistent with peroxisomal disorder

 

Identifying mutations within genes known to be associated with peroxisomal disorders, allowing for predictive testing of at-risk family members

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
CULFB Fibroblast Culture for Genetic Test Yes No
CULAF Amniotic Fluid Culture/Genetic Test Yes No
MATCC Maternal Cell Contamination, B Yes No

Testing Algorithm

See clinical information for recommended first-tier biochemical testing.

 

If skin biopsy is received, fibroblast culture will be added and charged separately.

 

For prenatal specimens only: If amniotic fluid (nonconfluent cultured cells) is received, amniotic fluid culture/genetic test will be added and charged separately. If chorionic villus specimen (nonconfluent cultured cells) is received, fibroblast culture for genetic test will be added and charged separately. For any prenatal specimen that is received, maternal cell contamination studies will be added.

 

See Newborn Screen Follow-up for X-Linked Adrenoleukodystrophy in Special Instructions.

Method Name

Custom Sequence Capture and Targeted Next-Generation Sequencing followed by Polymerase Chain Reaction (PCR) and Sanger Sequencing.

Reporting Name

Peroxisomal Disorder Panel

Specimen Type

Varies


Advisory Information


Due to the complexity of prenatal testing, consultation with the laboratory is required for all prenatal testing.



Additional Testing Requirements


All prenatal specimens must be accompanied by a maternal blood specimen.

-       Order MATCC / Maternal Cell Contamination, Molecular Analysis on the maternal specimen.



Shipping Instructions


Specimen preferred to arrive within 96 hours of collection.

 

Prenatal specimens can be sent Monday through Thursday and must be received by 5 p.m. CST on Friday in order to be processed appropriately.



Specimen Required


Submit only 1 of the following specimens:

 

Specimen Type: Whole blood

Container/Tube:

Preferred: Lavender top (EDTA) or yellow top (ACD)

Acceptable: Any anticoagulant

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send specimen in original tube.

Specimen Stability Information: Ambient (preferred)/Refrigerated

 

Specimen Type: Cultured fibroblasts

Container/Tube: T-75 or T-25 flask

Specimen Volume: 1 full T-75 or 2 full T-25 flasks

Specimen Stability Information: Ambient (preferred)/Refrigerated <24 hours

 

Prenatal Specimens

 

Specimen Type: Amniotic fluid

Container/Tube: Amniotic fluid container

Specimen Volume: 20 mL

Specimen Stability Information: Refrigerated (preferred)/Ambient

 

Specimen Type: Chorionic villi

Container/Tube: 15-mL tube containing 15 mL of transport media

Specimen Volume: 20 mg

Specimen Stability Information: Refrigerated

 

Acceptable

Specimen Type: Confluent cultured cells

Container/Tube: T-25 flask

Specimen Volume: 2 flasks

Collection Instructions: Submit confluent cultured cells from another laboratory.

Specimen Stability Information: Ambient (preferred)/Refrigerated

 

Specimen Type: Skin biopsy

Supplies: Fibroblast Biopsy Transport Media (T115)

Container/Tube: Sterile container with any standard cell culture media (eg, minimal essential media, RPMI 1640). The solution should be supplemented with 1% penicillin and streptomycin. Tubes can be supplied upon request (Eagle's minimum essential medium with 1% penicillin and streptomycin [T115]).

Specimen Volume: 4-mm punch

Specimen Stability Information: Refrigerated (preferred)/Ambient

 

Specimen Type: Blood spot

Supplies:

Preferred: Collection card (Whatman Protein Saver 903 Paper)

Acceptable: Ahlstrom 226 filter paper, or Card-Blood Spot Collection Filter paper (T493)

Specimen Volume: 3 to 5 Blood Spots on collection card

Collection Instructions:

1. An alternative blood collection option for a patient >1 year of age is finger stick.

2. Let blood dry on the filter paper at ambient temperature in a horizontal position for 3 hours.

3. Do not expose specimen to heat or direct sunlight.

4. Do not stack wet specimens.

5. Keep specimen dry

Specimen Stability Information: Ambient (preferred)/Refrigerated


Specimen Minimum Volume

Blood: 1 mL; Blood Spots: 3, 3-mm diameter; Amniotic Fluid: 10 mL; Chorionic Villi: 5 mg

Specimen Stability Information

Specimen Type Temperature Time
Varies Ambient (preferred)
  Frozen 
  Refrigerated 

Clinical Information

Peroxisomes are responsible for catabolic actions of cells, including beta oxidation of very long chain fatty acids, and anabolic actions, including biosynthesis of bile acids and plasmalogens. Peroxisomal disorders can be categorized into 2 major groups based on the function that is disrupted: peroxisomal biogenesis disorders and single peroxisomal enzyme deficiencies.

 

Peroxisomal biogenesis disorders are caused by defective assembly of the organelle resulting in some amount of deficient functional peroxisomes. Severity of disease is dependent on amount of remaining functional peroxisomes. Peroxisomal biogenesis disorders include the Zellweger spectrum: Zellweger syndrome, neonatal adrenoleukodystrophy, and infantile Refsum disease. Clinical features include developmental delay, liver disease, blindness, and deafness, and are usually progressive. Severity is variable with Zellweger syndrome being most severe and infantile Refsum disease being least severe.

These are due to mutations in the PEX genes that are responsible for encoding proteins for peroxisome assembly.

 

Peroxisomal enzyme deficiencies cause a disruption in peroxisomal function, although the organelles remain intact. The most common peroxisomal disorder, X-linked adrenoleukodystrophy, is an enzyme deficiency due to mutations in the ABCD1 gene. Other enzyme deficiencies include rhizomelic chondrodysplasia type 2 and 3, and congenital bile acid synthesis defect.

 

Preliminary biochemical testing may be helpful in making a diagnosis. Recommended first-tier biochemical testing for peroxisomal disorders analyzes very long chain fatty acids is POX / Fatty Acid Profile, Peroxisomal [C22-C26], Serum.

 

This panel includes sequencing of 30 genes related to both peroxisomal biogenesis disorders and enzyme deficiencies. See table below for additional information.

 

Gene

Disease Name/Locus Name

OMIM ID

Inheritance

ABCD1

X-linked adrenoleukodystrophy

300100

XL

ABCD2

Adrenoleukodystrophy-like/related

601081

XL

ABCD3

Congenital bile acid synthesis defect-5

616278

AR

ACOX1

Acyl-CoA oxidase deficiency

264470

AR

ACOX3

None at present time

603402

NA

AGPS

Rhizomelic chondrodysplasia punctate, type 3 (RCDP)

600121

AR

AMACR

Alpha-methylacyl-CoA racemase deficiency; bile acid synthesis defect, congenital,

614307, 214950

AR

CAT

Acatalasemia

614097

AR

DNM1L

Encephalopathy, lethal, due to defective mitochondrial and peroxisomal fission

614388

AD

ECH1

 None at present time

600696

 NA

GNPAT

Rhizomelic chondrodysplasia punctata, type 2 (RCDP)

222765

AR

HSD17B4

D-bifunctional enzyme deficiency; Perrault syndrome

261515, 233400

AR

PEX1

Zellweger; peroxisome biogenesis disorder

214100

AR

PEX10

Zellweger; peroxisome biogenesis disorder

614871

AR

PEX11B

Zellweger; peroxisome biogenesis disorder

614920

AR

PEX12

Zellweger; peroxisome biogenesis disorder

614859, 266510

AR

PEX13

Zellweger; peroxisome biogenesis disorder

614885, 614883

AR

PEX14

Zellweger; peroxisome biogenesis disorder

614887

AR

PEX16

Zellweger; peroxisome biogenesis disorder

614877, 614876

 

AR

PEX19

Zellweger; peroxisome biogenesis disorder

614886

AR

PEX2

Zellweger; peroxisome biogenesis disorder

614867, 614866

AR

PEX26

Zellweger; peroxisome biogenesis disorder

614872, 614873

AR

PEX3

Zellweger; peroxisome biogenesis disorder

614882

AR

PEX5

Zellweger; peroxisome biogenesis disorder

202370, 214110

AR

PEX6

Zellweger; peroxisome biogenesis disorder

614863, 614862

AR

PEX7

Rhizomelic chondrodysplasia punctate, type 1 (RCDP)

215100, 614879

AR

PHYH

Refsum disease

266500

AR

SCP2

Leukoencephalopathy with dystonia and motor neuropathy

613724

AR

SUGCT

Glutaric aciduria III

231690

AR

TRIM37

Mulibrey nanism

253250

AR

AR=autosomal recessive

AD=autosomal dominant

Reference Values

An interpretive report will be provided.

Interpretation

All detected alterations are evaluated according to American College of Medical Genetics and Genomics recommendations.(1) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

 

Multiple in silico evaluation tools may be used to assist in the interpretation of these results. The accuracy of predictions made by in silico evaluation tools is highly dependent upon the data available for a given gene, and predictions made by these tools may change over time. Results from in silico evaluation tools should be interpreted with caution and professional clinical judgment.

Clinical Reference

1. Richards S, Aziz N, Bale S, et al: Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015 May;17(5):405-424

2. Waterham, HR, Ebberink MS: Genetics and molecular basis of human peroxisome biogenesis disorders. Biochim Biophys Acta 2012;1822(9):1430-1441

3. Wanders RJ: Metabolic and molecular basis of peroxisomal disorders: a review. Am J Med Genet A 2004;126A(4):355-375

4. Wanders RJ, Waterham HR: Peroxisomal disorders: the single peroxisomal enzyme deficiencies. Biochim Biophys Acta 2006;1763(12):1707-1720

5. Fidaleo M: Peroxisomes and peroxisomal disorders: the main facts. Exp Toxicol Pathol 2010;62(6): 615-625

Day(s) and Time(s) Performed

Performed weekly, Varies

Analytic Time

4 weeks

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.

CPT Code Information

81405

81479

Fibroblast Culture for Genetic Test

88233-Tissue culture, skin or solid tissue biopsy (if appropriate)

88240-Cryopreservation (if appropriate)

Amniotic Fluid Culture/Genetic Test

88235-Tissue culture for amniotic fluid (if appropriate)

88240-Cryopreservation (if appropriate)

Maternal Cell Contamination, B

81265-Comparative analysis using Short Tandem Repeat (STR) markers; patient and comparative specimen (eg, pre-transplant recipient and donor germline testing, post-transplant non-hematopoietic recipient germline [eg, buccal swab or other germline tissue sample] and donor testing, twin zygosity testing or maternal cell contamination of fetal cells (if appropriate)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
PDP Peroxisomal Disorder Panel In Process

 

Result ID Test Result Name Result LOINC Value
41775 Result Summary 50397-9
41776 Result In Process
41777 Interpretation In Process
41778 Additional Information 48767-8
41779 Specimen In Process
41780 Source 31208-2
41781 Released By No LOINC Needed

Forms

1. New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (T576) is available in Special Instructions.

2. Molecular Genetics Molecular Genetics: Biochemical Disorders Patient Information (T527) in Special Instructions

Mayo Medical Laboratories | Genetics and Pharmacogenomics Catalog Additional Information:

mml-inherited-molecular