| dc.description.abstracteng | There are about 15 peroxisomal disorders known today. The zellweger syndrome spectrum is one of the peroxisomal biogenesis disorders and x-adrenoleukodystrophy belongs to a group that is characterized by individual peroxisomal protein dysfunctions. Among other things, peroxisomes are responsible for the beta-oxidation of long-chain fatty acids. However, they also play an important role in the synthesis of polyunsaturated fatty acids and bile acids. Typically, long-chain fatty acids, which cause neurotoxic-inflammatory and demyelenating processes, accumulate in various tissues and especially in the neuronal tissue of patients. Furthermore, there are severe malformations and dysfunctions of several organs in newborns and infants, which clinically manifest themselves as seizures, muscular hypotonia, loss of vision, hepatosplenomegaly or craniofacial dysmorphism. The prognosis for patients suffering from Zellweger syndrome is usually poor and many patients do not reach the first year of life. The diagnosis is currently carried out using mass spectrometry and genetic analysis. In most cases, samples or patients have to be referred to specific clinics with special laboratories. Therapeutically, there are some approaches, which, however, only help symptomatically and do not treat the disease causally. Even gene therapies have not brought the desired results so far. Due to the complex diagnostics and the lack of therapy, there is still a lot to learn about peroxisomal diseases such as Zellweger syndrome and x-adrenoleukodystrophy. Therefore, new biomarkers should characterize the diseases better and help to understand the metabolic changes. They can serve as a starting point for new, more sensitive diagnostic methods or even therapeutic methods and make it easier to differentiate between the diseases.
Blood samples from 12 Zellweger syndrome patients with the most common mutation (PEX1), 12 suffering from x-adrenoleukodystrophy and 12 control samples were examined. The blood samples were hydrolyzed pre-analytically and then a method of ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS/MS) was used. The data were evaluated on the chromatogram and with data processing software, as well as descriptive statistics.
First of all, the stability of the measurement method could be shown and some of the previously known biomarkers could be detected and brought into line with other research results. In addition, new biomarkers were found in the blood of the patients with the measuring method, which can be interpreted as hexacosadienoic acid, calcitriol, pentacosenoic acid and octacosenoic acid. Furthermore, sphingomyelin 24:0 was analyzed in the blood of the patients, which can serve as a starting point for further quantifying measurements. | de |