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Peroxisomal functions in classical Refsum's disease: comparison with the infantile form of Refsum's disease
R J Wanders1, H S Heymans, R B Schutgens
1Dept. of Pediatrics, University Hospital Amsterdam, The Netherlands.
Insights
Classical Refsum's disease shows normal peroxisomal functions, unlike the infantile form. This suggests classical Refsum's disease may not be a peroxisomal disorder, highlighting distinct disease entities.
Area of Science:
- Biochemistry
- Genetics
- Metabolic Disorders
Background:
- Refsum's disease, encompassing infantile and classical forms, is often classified with peroxisomal disorders.
- Peroxisomal disorders involve defects in peroxisome function, impacting various metabolic pathways.
Purpose of the Study:
- To investigate peroxisomal functions in classical Refsum's disease.
- To differentiate classical Refsum's disease from infantile Refsum's disease by comparing peroxisomal function profiles.
Main Methods:
- Analysis of plasma markers: very long chain fatty acids, di- and trihydroxycoprostanoic acid, and pipecolic acid.
- Assessment of cultured skin fibroblasts: de novo plasmalogen biosynthesis, very long chain fatty acid oxidation, and catalase levels.
- Comparison of functional data between classical Refsum's disease patients and infantile Refsum's disease.
Main Results:
- Peroxisomal functions were generally normal in classical Refsum's disease.
- A deficiency in phytanic acid oxidation was observed in classical Refsum's disease.
- Infantile Refsum's disease exhibited a general impairment of peroxisomal functions.
Conclusions:
- Peroxisomal biogenesis appears normal in classical Refsum's disease, but impaired in infantile Refsum's disease.
- Classical and infantile Refsum's disease represent distinct clinical and etiological entities.
- The role of peroxisomes in classical Refsum's disease requires further investigation, as phytanic acid oxidation may occur in mitochondria.
Abstract:
The infantile and classical forms of Refsum's disease are generally considered to belong to the newly recognized group of peroxisomal disorders. In this study we carried out a detailed investigation into different peroxisomal functions in classical Refsum's disease by analyses of plasma (very long chain fatty acids, di- and trihydroxycoprostanoic acid and pipecolic acid) and cultured skin fibroblasts from the patients (de novo plasmalogen biosynthesis, very long chain fatty acid oxidation and amount of particle-bound catalase). The results obtained indicate that, except for a deficient phytanic acid oxidation, peroxisomal functions were found to be normal in classical Refsum's disease in contrast with the findings in infantile Refsum's disease, in which there is a general impairment of peroxisomal functions. Based on these results it is concluded that peroxisomal biogenesis is normal in classical (but not in infantile) Refsum's disease and that the classical and infantile form of Refsum's disease hence represent distinct entities. Since available evidence suggests that phytanic acid is oxidized in mitochondria rather than in peroxisomes, at least in rat liver, it remains to be established whether classical Refsum's disease is a peroxisomal disorder or not.