Table 1 Peroxisome functions and their biochemical consequences and possible clinical relevance in ZSDs
From: Zellweger spectrum disorders: clinical overview and management approach
Peroxisome function | Biochemical consequence | Possible clinical relevance |
|---|---|---|
β-oxidation of VLCFA (≥C22) | Impaired chain shortening of VLCFA, last step in DHA synthesis is impaired | Brain, nerve and adrenal damage due to VLCFA tissue accumulation, DHA deficiency affects brain function and vision |
β-oxidation of methyl-branched chain fatty acid, DHCA and THCA | Impaired chain shortening of DHCA, THCA and pristanic acid | Pristanic acid accumulation affects brain function, accumulation of DHCA and THCA causes liver toxicity and probably also brain damage |
α-oxidation of fatty acids | Impaired (pre-) degradation of methyl branched phytanic acid | Retinal degeneration, brain and nerve damage due to phytanic acid accumulation |
Fatty acid racemization | Reduced convertion of pristanoyl-CoA and C27-bile acyl-CoAs into stereoisomers before β-oxidation | Tissue accumulation of DHCA, THCA, pristanic- and phytanic acid |
Ether phospholipid (plasmalogen) biosynthesis | Impaired formation of ether phospholipids | Plasmalogen deficiency gives rise to growth- and psychomotor retardation, cataract and bone development anomalies |
Glyoxylate detoxification | Conversion of glyoxylate into oxalate, a toxic metabolite | Accumulation leads to calcium oxalate renal stones |
L-lysine oxidation | Impaired L-pipecolic acid degradation | Accumulation of pipecolic acid, no clinical consequences known [78] |
Hydrogen peroxide detoxification | Decreased catabolism of hydrogen peroxide | Increased reactive oxidant damage |