Диагностика пероксисомных заболеваний - от биохимических тестов к молекулярным и vice versa

The main laboratory test for the diagnosis of peroxisome diseases (PD) is the analysis of the concentration of very long chain fatty acids (VLCFA), their ratios, phytanic and pristanic acids in plasma. Until the beginning of 2017, only the detection of VLCFA and the analysis of several genes: ABCD1 , PEX1 , PEX6 were used to diagnose PD in the laboratory of inherited metabolic diseases (IMD). The purpose of the work was to expand the range of biochemical and DNA-tests to increase the effectiveness of diagnosis of PD. The analysis of the simultaneous determination of VLCFA, their ratios, phytanic and pristanic acids by gas chromatography-mass spectrometry (GC-MS) was tested, which allows to carry out confirmatory biochemical test. A target panel was developed that includes 15 genes of PEX, as well as genes responsible for X-ALD, Refsum’s disease and D-bifunctional protein deficiency for molecular genetic verification of the diagnosis. Using this approach, changes in the concentration of these metabolites were detected in 13 patients and the following diagnoses were verified on the basis of clinical data and the results of DNA diagnostics: D-bifunctional protein deficiency (n = 1), Zellweger syndrome (n = 1), X-linked adrenoleukodystrophy (n = 11). In 2 patients biochemical tests were used to confirm the pathogenicity of mutations detected during DNA diagnostics: Zellweger syndrome (n = 1), X-linked adrenoleukodystrophy (n = 1).