Peroxisomal Diseases

Director:

Richard Jones, PhD
Phone: (443) 923-2788
Fax: (443) 923-2755
Email: jonesri@kennedykrieger.org

About the Peroxisomal Diseases Laboratory:

The Peroxisomal Diseases Section of the Genetics Laboratories assays blood, urine, fibroblasts and cultured CVS/amniocytes for fatty acid abnormalities associated with diseases such as Adrenoleukodystrophy, Adult Refsum Disease, Zellweger Spectrum Disorders, and Rhizomelic Chondrodysplasia Punctata Type 1.

We also assay plasma and red blood cells for nutritional content and DHA.

Indications for Peroxisomal Disease Screening:

The criteria for testing for a peroxisomal disease is very broad and is evolving. The following are offered as some characteristic features seen at particular ages.

  • Neonates:
    • unusual facies
    • hypotonia
    • shortened limbs
    • stippled epiphyses
    • enlarged liver
    • cataracts
    • seizures
    • failure to thrive
  • Children:
    • intellectual disability
    • loss of previously attained function
    • leukodystrophy
    • adrenal hypo/hyperplasia
    • visual defect/retinal dysplasia
    • spasticity
    • attention deficit onset
    • behavioral changes
  • Adults
    • peripheral neuropathy
    • Retinitis pigmentosa
    • Sensorineural hearing loss
    • Prenatal diagnosis available for families with previous positive diagnoses

Peroxisomal Disease Tests:

Very Long Chain Fatty Acids

Plasma from EDTA-treated whole blood is treated to extract fatty acids from circulating complex lipids and free fatty acids. The very long chain fatty acids (C20:0 to C26:0) as well as the branched chain fatty acids (phytanic and pristanic) are identified by gas chromatography/mass spectrometry and the values (ug/ml) compared to our normal and disease control values.

We also provide tandem mass spectrometry (LC-MS/MS) on dried blood spots to measure C26:0-lyso phosphatidylcholine for newborn screening of peroxisomal diseases.

Plasma Fatty Acid Profile

Plasma from EDTA-treated whole blood is treated to extract fatty acids from circulating complex lipids and free fatty acids. The sample is analyzed by gas chromatography/mass spectrometry. A total of 57 fatty acids from C10:0 through C30:0 as well as useful ratios and group summaries (e.g. total w6 fatty acids including the essential fatty acid linoleic acid) are reported and compared to our normal control values.

Red Blood Cell Fatty Acid Profile

Red blood cells from EDTA-treated whole blood are washed free of plasma and treated to extract fatty acids from membrane complex lipids and free fatty acids. The sample is analyzed by gas chromatography/mass spectrometry. A total of 57 fatty acids from C10:0 through C30:0 as well as useful ratios and group summaries (e.g. total w6 fatty acids including the essential fatty acid linoleic acid) are reported and compared to our normal control values.

Plasmalogens

Red blood cells from EDTA-treated whole blood are washed free of plasma and treated to extract fatty acids from complex membrane lipids. Plasmalogens in the form of dimethylacetals (DMAs) are identified by gas chromatography and the DMA/fatty acid ratios (C16:0DMA/C16:0 and C18:0DMA/C18:0) are compared to our normal and disease control values.

Pipecolic Acid

Plasma from EDTA-treated whole blood (or urine from neonates) is treated to extract fatty acids from circulating complex lipids and free fatty acids. Pipecolic acid is identified by gas chromatography/mass spectrometry and the values (umol/L) compared to our normal and disease control values.

DHA (Docosahexanoic Acid)

Red blood cells from EDTA-treated whole blood are washed free of plasma and treated to extract fatty acids from complex membrane lipids. DHA is identified by gas chromatography/mass spectrometry and the value (percentage of Total Lipid Content) compared to our normal and disease control values.

Fibroblast Fatty Acid Analysis

Cells are cultured in our own media and treated to extract fatty acids from complex membrane lipids. The very long chain fatty acids (C22:0 to C26:0) are identified by gas chromatography and the values (ug/ml /mg protein) compared to our normal and disease control values.

Fibroblast Peroxisomal Enzymes (catalase, plasmalogen synthesis, phytanic acid oxidase, pristanic acid oxidase)

In the assay of catalase, cultured cells are treated and the distribution of catalase (an enzyme that is normally localized in the peroxisome) between the cytoplasm and peroxisome is determined. The values (percentage of soluble catalase) are compared to our normal and disease control values.

The other enzyme tests are performed on cells cultured in our own media and labeled with radioisotope tracers. The enzyme activity is compared to our normal and disease control values.

Prenatal Testing for Peroxisomal Disorders

We can test cultured chorionic villus cells (CVS) or cultured amniocytes for the presence of peroxisomal disorders such as X-linked Adrenoleukodystrophy, Zellweger Spectrum Disorders and Rhizomelic Chondrodysplasia Punctata Type 1 in families with a history of these disorders. The assays include very long chain fatty acids and/or plasmalogen synthesis enzymes and are performed in the same manner as in cultured fibroblasts. Results are compared to our normal and disease control values for prenatal cells.