From the Guidelines
Peroxisomal biogenesis disorders are characterized by a distinct plasma lipid profile, including elevated very long-chain fatty acids (VLCFAs), specifically C26:0 and C26:1, as well as increased C26:0/C22:0 and C24:0/C22:0 ratios, as noted in a study published in 2020 1. The plasma lipid profile in peroxisomal biogenesis disorders is marked by several key abnormalities, including:
- Elevated very long-chain fatty acids (VLCFAs), particularly C26:0 and C26:1
- Increased C26:0/C22:0 and C24:0/C22:0 ratios
- Reduced plasmalogens
- Elevated phytanic and pristanic acids
- Abnormal bile acid intermediates in plasma These lipid abnormalities are a direct result of impaired peroxisomal function, as peroxisomes play a crucial role in metabolizing VLCFAs through beta-oxidation, synthesizing plasmalogens, and processing branched-chain fatty acids, as discussed in the context of polymicrogyria and peroxisomal disorders 1. In the diagnostic work-up for peroxisomal biogenesis disorders, measurement of these specific lipid parameters is essential, with VLCFA analysis being the first-line screening test, particularly in cases where a peroxisomal disorder is suspected, such as in patients with polymicrogyria who are unusually sick in the neonatal period or early infancy 1.
From the Research
Peroxisomal Biogenesis and Plasma Lipid Profile
The plasma lipid profile in peroxisomal biogenesis disorders is characterized by:
- Aberrant lipid metabolism, including changes in phospholipids, di- and triglycerides, and cholesterol esters 2
- Accumulation of very long-chain fatty acids (VLCFAs) and monounsaturated fatty acids in phosphatidylcholine 3
- Elevated levels of VLCFAs, including C26:0, C26:0/C22:0, and C24:0/C22:0 4
- Increased levels of phytanic acid and malonedialdhyde (MDA) 4
- Decreased levels of plasmalogen and high-density lipoprotein-cholesterol (HDL-C) 4
- No significant difference in cholesterol and triglycerides between patients and controls 4
Biomarkers for Peroxisomal Biogenesis Disorders
Biomarkers that have been identified for peroxisomal biogenesis disorders include:
- VLCFAs, which are the most significant diagnostic markers for PBD 4
- Phytanic acid, MDA, and catalase activity 4
- Plasmalogen and HDL-C levels 4
- Inflammatory markers, such as tumor necrosis-alpha, interleukin-6, and interleukin-2 (TNF-alpha, IL-6, and IL-2) 4
Diagnostic Approaches
Diagnostic approaches for peroxisomal biogenesis disorders include: