Abstract
Peroxisomes are dynamic organelles that play an essential role in a variety of metabolic pathways. Peroxisomal dysfunction can lead to various biochemical abnormalities and result in abnormal metabolite levels, such as increased very long-chain fatty acid or reduced plasmalogen levels. The metabolite abnormalities in peroxisomal disorders are used in the diagnostics of these disorders. In this paper we discuss in detail the different diagnostic tests available for peroxisomal disorders and focus specifically on the important role of biochemical and functional studies in cultured skin fibroblasts in reaching the right diagnosis. Several examples are shown to underline the power of such studies.
Highlights
Peroxisomal disorders form a group of inherited disorders caused by mutations in genes encoding peroxisomal proteins, which lead to one or more impaired peroxisomal functions or cause the absence of functional peroxisomes altogether
A defect of one or more functions of the peroxisome leads to abnormal metabolite levels, which is used in the screening for peroxisomal disorders (Wanders and Waterham 2006a, b; Van Veldhoven 2010)
The different peroxisomal disorders known to date and the peroxisomal metabolic pathways that are affected in these disorders are summarized in Table 1, but will not be discussed in detail in this paper, which focuses primarily on the diagnostics of peroxisomal disorders
Summary
Mosaic pattern at Mosaic pattern at 37 °C, 37 °C, negative at negative at 40 °C 40 °C. At the very mild end of the ZSD spectrum, in patients presenting with Heimler syndrome, the only identified abnormality in the extensive peroxisomal screening in blood and fibroblasts performed, was the aberrant peroxisomal staining with immunofluorescence microscopy analysis, which exacerbated after culturing the fibroblasts at 40 °C This means that when the clinical symptoms of a patient are suggestive of a peroxisomal disorder but peroxisomal metabolites in blood and urine are normal, studies in fibroblasts are still warranted. In a 5-year old boy presenting with hypotonia and abnormal pain sense in the legs, secondary enuresis and normal cognition, X-ALD was suspected after VLCFA analysis in blood was abnormal This suspicion initially seemed not confirmed by mutation analysis of ABCD1, which revealed a hemizygous c.1-22C > T variant that had not been reported previously but was not predicted as pathogenic. These last two tests can be performed in cultured amniocytes but this is not preferred because the interpretation is more difficult and only two tests can be performed as opposed to four different tests in chorionic villous material
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