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Test ID: PGDBS Plasmalogens, Blood Spot


Additional Testing Requirements


If peroxisomal biogenesis disorders (Zellweger syndrome spectrum) are suspected, also order very long chain fatty acids (POX / Fatty Acid Profile, Peroxisomal [C22-C26], Serum; or POXP / Fatty Acid Profile, Peroxisomal [C22-C26], Plasma), bile acids (BAIPD / Bile Acids for Peroxisomal Disorders, Serum), and pipecolic acid (PIPU / Pipecolic Acid, Urine).

 

If rhizomelic chondrodysplasia punctata (RCDP) is suspected, also order very long chain fatty acids (POX / Fatty Acid Profile, Peroxisomal [C22-C26], Serum), which includes phytanic and pristanic acid analysis.



Necessary Information


-Reason for testing is required

-Date of blood transfusion, if performed.

-Biochemical Genetics Patient Information (T602) is recommended, but not required, to be filled out and sent with the specimen to aid in the interpretation of test results.

Specimen Required


Specimen must be collected either prior to or 6 weeks after a blood transfusion.

 

Submit only 1 of the following specimens:

Preferred:

Specimen Type: Blood spot

Supplies: Card-Blood Spot Collection (Filter Paper) (T493)

Container/Tube:

Preferred: Blood spot collection card

Acceptable: PerkinElmer 226 (formerly Ahlstrom 226) filter paper, Munktell filter paper, Whatman Protein Saver 903 paper, or blood collected in tubes containing ACD, EDTA, or heparin spotted and dried on filter paper

Specimen Volume: 2 blood spots

Collection Instructions:

1. An alternative blood collection option for a patient older than 1 year of age is fingerstick. See Dried Blood Spot Collection Tutorial for how to collect blood spots via fingerstick: https://vimeo.com/508490782 .

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

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

4. Do not stack wet specimens.

5. Keep specimen dry.

Additional Information:

1. For collection instructions, see Blood Spot Collection Instructions in Special Instructions.

2. For collection instructions in Spanish, see Blood Spot Collection Card-Spanish Instructions (T777) in Special Instructions.

3. For collection instructions in Chinese, see Blood Spot Collection Card-Chinese Instructions (T800) in Special Instructions.

 

Acceptable

Specimen Type: Whole Blood

Container/Tube:

Preferred: Lavender top (EDTA)

Acceptable: Green top (sodium or lithium heparin), yellow top (ACD solution A or ACD solution B)

Specimen Volume: 2 mL

Collection Instructions: Send specimen in original tube.

Specimen Stability Information: Refrigerate (preferred) 14 days/Ambient 11 days


Forms

Biochemical Genetics Patient Information (T602) in Special Instructions.

Useful For

Diagnosing patients with possible peroxisomal disorders, such as peroxisomal biogenesis disorders (Zellweger syndrome spectrum) and rhizomelic chondrodysplasia punctata (RCDP), including fatty acyl-CoA reductase 1 (FAR1) deficiency.

 

Evaluating patients with abnormal newborn screen results for X-linked adrenoleukodystrophy who appear to have a different type of peroxisomal disorder such as a Zellweger syndrome spectrum disorder.

 

An aid in the assessment of peroxisomal function

Method Name

Gas Chromatography/Mass Spectrometry (GC-MS)

Reporting Name

Plasmalogens, BS

Specimen Type

Whole blood

Specimen Minimum Volume

Blood Spots: 1
Whole Blood: 0.5 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Whole blood Varies

Clinical Information

Peroxisomes are organelles that carry out essential metabolic functions including beta-oxidation of very long-chain fatty acids (VLCFA), alpha-oxidation of phytanic acid, and biosynthesis of plasmalogen and bile acids. Peroxisomal disorders include disorders of peroxisomal biogenesis with defective assembly of the entire organelle, and disorders of peroxisome function with single peroxisomal enzyme/transporter defects where the organelle is intact, but a specific function is disrupted.

 

Biochemical abnormalities in peroxisomal biogenesis disorders can include accumulations of VLCFA, phytanic, and pristanic acid, pipecolic acid, bile acids, and reduced plasmalogens. The differential diagnosis of these disorders is based on recognition of clinical phenotypes combined with a series of biochemical tests to assess peroxisomal function and structure. These include measurements and ratios of VLCFA, phytanic acid, and its metabolite pristanic acid (POX / Fatty Acid Profile, Peroxisomal [C22-C26], Serum or POXP / Fatty Acid Profile, Peroxisomal [C22-C26], Plasma), pipecolic acid (PIPA / Pipecolic Acid, Serum or PIPU / Pipecolic Acid, Urine), bile acids (BAIPD / Bile Acids for Peroxisomal Disorders, Serum), and plasmalogens.

 

Peroxisomal biogenesis disorders (PBD) include the Zellweger syndrome spectrum disorders, which are clinically diverse and range in severity from neonatal lethal (Zellweger syndrome) to more variable clinical courses in neonatal adrenoleukodystrophy and infantile Refsum disease. Affected children typically have hypotonia, poor feeding, distinctive facial features, seizures, and liver dysfunction. Other features can include retinal dystrophy, hearing loss, developmental delays, and bleeding episodes.

 

Rhizomelic chondrodysplasia punctata (RCDP) is a malformation disorder characterized by rhizomelic shortening, chondrodysplasia punctata, cataracts, intellectual disability, and seizures, although it can have a milder phenotype with only cataracts and chondrodysplasia punctata. Currently, there are 5 clinical types of rhizomelic chondrodysplasia punctata: RCDP 1, 2, 3, 4 (also known as FAR1 deficiency) and 5. RCDP 1 is the classical form that presents in infancy with skeletal manifestations including rhizomelic shortening, cataracts, and severe to profound postnatal growth deficiency. Infants with RCDP 1 have developmental delay, and later, intellectually disability. The majority of children with RCDP 1 do not survive beyond the first decade of life. RCDP 1 is an autosomal recessive disorder caused by pathogenic variants in the PEX7 gene. RCDP 2 and 3 have clinical phenotypes similar to RCDP 1 and may be distinguished by plasmalogen deficiency. RCDP 2 and 3 are autosomal recessive conditions caused by pathogenic variants in GNPAT and AGPS genes, respectively. Individuals with RCDP 5 have a milder phenotype when compared to classic RCDP 1, with most individuals able to achieve self-feeding, independent ambulation, and development of limited language skills. RCDP5 results in less pronounced reduction in plasmalogens compared to RCDP 1. This newly recognized subtype of RCDP is an autosomal recessive disorder caused by pathogenic variants in the PEX5 gene.

 

The typical biochemical profile for RCDP shows reduced plasmalogens, elevated phytanic acid, and normal VLCFA. Confirmatory testing via molecular analysis for all types of RCDP is available (PDGD / Peroxisomal Disorder Gene Panel, Varies).

 

Fatty acyl-CoA reductase 1 (FAR1) deficiency, also known as RCDP type 4, is an autosomal recessive peroxisomal disorder caused by pathogenic variants in the FAR1 gene that result in early-onset epilepsy, microcephaly, cataracts, postnatal growth deficiency, and intellectual disability. Unlike RCDP, however, infants with FAR1 deficiency have no skeletal abnormalities. The biochemical profile for FAR1 deficiency includes reduced plasmalogens, normal to elevated phytanic acid, and normal VLCFA.

Reference Values

Hexadecanal-Dimethylacetal, C16:0 DMA

> =7.00 mcg/mL

 

Octadecanal-Dimethylacetal, C18:0 DMA

> =12.00 mcg/mL

 

9Z-Octadecenal-DiMe acetal C18:1DMA

> =2.00 mcg/mL

 

C16:0 DMA/C16:0

> =0.012

 

C18:0 DMA/C18:0

> =0.050

Interpretation

Reports include concentrations of C16:0, C18:0 and C18:1 plasmalogens and the ratio of the C16:0 and C18:0 plasmalogens to the respective fatty acid. When no significant abnormalities are detected, a simple descriptive interpretation is provided.

 

A profile of reduced plasmalogens and abnormal very long-chain fatty acids (VLCFA), as well as possible abnormalities in pipecolic acid and bile acids, can be consistent with a diagnosis of a peroxisomal biogenesis disorder (Zellweger syndrome spectrum).

 

A profile of reduced plasmalogens, elevated phytanic acid, and normal VLCFA is consistent with a diagnosis of rhizomelic chondrodysplasia punctata, such as RCDP type 1 or 2, FAR1 deficiency (RCDP type 4), or other types of RCDP.

 

Positive test results could be due to a genetic or nongenetic condition. Additional confirmatory testing would be required to differentiate between these causes.

Clinical Reference

1. Braverman NE, Moser AB, Steinberg SJ, Fallatah WF, Duker A, Bober M: Rhizomelic chondrodysplasia punctata type 1. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 2001. Updated January 30, 2020. Accessed May 20, 2020. Available at www.ncbi.nlm.nih.gov/books/NBK1270/

2. Buchert R, Tawamie H, Smith C, et al. A peroxisomal disorder of severe intellectual disability, epilepsy, and cataracts due to fatty acyl-CoA reductase 1 deficiency. Am J Hum Genet. 2014 Nov 6;95(5):602-610

3. Baroy T, Koster J, Stromme P, et al. A novel type of rhizomelic chondrodysplasia punctata, RCDP5, is caused by a loss of the PEX5 long isoform. Hum Mol Genet. 2015;24(20):5845-5854

4. Braverman NE, Moser AB: Functions of plasmalogen lipids in health and disease. Biochim Biophys Acta. 2012;1822(9):1442-1452

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

82542

LOINC Code Information

Test ID Test Order Name Order LOINC Value
PGDBS Plasmalogens, BS In Process

 

Result ID Test Result Name Result LOINC Value
609665 Hexadecanal-Dimethylacetal, C16 DMA In Process
609666 Octadecanal-Dimethylacetal, C18 DMA In Process
609667 9Z-Octadecenal-DiMe acetal C18:1DMA In Process
609670 C16 DMA/C16:0 In Process
609671 C18 DMA/C18:0 In Process
BG724 Reason for Referral 42349-1
609673 Reviewed By 18771-6
609674 Interpretation 59462-2

Day(s) Performed

Wednesday

Report Available

3 to 9 days
Mayo Clinic Laboratories | Genetics and Pharmacogenomics Catalog Additional Information:

mml-biochemical