A nationwide blood spot screening study for Fabry disease in the Czech Republic haemodialysis patient population.

BACKGROUND: Fabry disease (FD) is a genetic disorder characterized by accumulation of trihexosylceramide in lysosomes of various tissues leading to multiorgan manifestations, including progressive renal disease. Previous screening studies have shown that a non-neglectable proportion of haemodialysis(HD) patients have unsuspected FD. An extensive FD screening study, the largest to date, has been conducted in HD patients in Czech Republic. We aimed to uncover previously undiagnosed FD patients, to enable them to benefit from cause-specific therapeutic intervention with enzyme replacement therapy (ERT). METHODS: Large-scale screening was executed using a convenient automated enzymatic (alpha-galactosidose A, alpha-Gal A) dried blood spot on filter paper fluorescence method. RESULTS: In total, 3370 (45.1% males, 54.9% females) out of 4058 HD patients (83%) in Czech Republic participated in this blood spot screening (BSS) study. Abnormal low fluorescence readings were obtained in 117 patients (3.5%). Subsequent determination of plasma alpha-Gal A activity identified four males and three females with deficient plasma enzyme activity. Determination of alpha-Gal A activity in peripheral blood leucocytes and confirmatory molecular analysis resulted in four newly diagnosed Fabry males and one female. Subsequent family screening identified 10 family members with genotypically proven FD. Based on these screening results, ERT could be offered to five male FD patients. CONCLUSIONS: BSS represents a promising screening tool that has proven to be convenient and effective in uncovering unrecognized FD patients among the chronic HD population in Czech Republic.

An evaluation of the influence of therapeutic interventions on serum trace element levels in groups of patients.

The aim of the study was to propose a method of large amount data evaluation. A new graphical method for data evaluation was suggested: the data were ranked according to the initial values and both the initial values and final values were intersected by polynomial curves. This method was used in the following situations: 1. Serum levels of Mg and Zn were measured just before and after hemodialysis (HD) in 87 patients in chronic renal failure. 2. Mg levels in serum, red blood cells and urine were estimated in 20 patients before and after administration of a Mg containing drug. Three basic graphic forms of curves were established: 1. Significant decrease of serum Mg levels during HD resulted in two uncrossed lines, the initial-values line being higher than terminal-values one (the higher the initial level the more pronounced was its decrease during HD). 2. Balanced effect of HD on the serum levels of Zn (low values increased, high levels decreased) represented two crossing-lines. 3. Significant increase of urine Mg in patients supplemented by Mg demonstrated two uncrossed lines. The position of initial-values curve was lower than the terminal-values one. The proposed graphical method of the evaluation of large amounts of data is simple and enables a quick orientation in the assessment of the effects of therapeutic interventions (trace elements, drugs and other relevant substances).