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The relative frequency of the common phenylalanine hydroxylase (PAH) mutation R408W and its associations with polymorphic RFLP, VNTR, and short-tandem-repeat (STR) sites in the PAH gene were examined in many European populations and one representative North American population of defined European descent. This mutation was found to cluster in two regions: in northwest Europe among Irish and Scottish peoples, and in eastern Europe, including the Commonwealth of Independent States. This allele was significantly less frequent in intervening populations. In eastern European populations, the R408W mutation is strongly associated with RFLP haplotype 2, the three-copy VNTR allele (VNTR 3), and the 240-bp STR allele. In northwestern European populations, it is strongly associated with RFLP haplotype 1, the VNTR allele containing eight repeats (VNTR 8), and the 244-bp STR allele. An examination of the linkage between the R408W mutation and highly polymorphic RFLP, VNTR, and STR haplotypes suggests that recurrence is the most likely mechanism to account for the two different major haplotype associations of R408W in Europe. more...

This short communication compares a novel fluorimetric microplate enzyme immunoassay (FEIA) with a commercial time-resolved fluoroimmunoassay for the determination of thyrotropin in dried blood spots. The evaluation was performed using a retrospective study design with newborn blood samples from three screening centres. Non-parametric Spearman rank correlation analysis revealed highly significant positive correlation between methods: rs = 0.465, p < 0.0001 (Hannover), rs = 0.659, p < 0.0001 (Minsk), rs = 0.755, p < 0.0001 (Helsinki). Wilcoxon signed rank test performed for paired FEIA and time-resolved fluoroimmunoassay showed that the results obtained by both tests represented the same distribution (p < 0.0001). The new method, using fluorimetric detection, can be performed with the instrumentation commonly used for the screening of congenital hypothyroidism and phenylketonuria. Results are obtained within three to four hours after arrival of the sample in the laboratory. Preliminary evaluation indicates the method to be a suitable alternative to time-resolved fluoroimmunoassay for neonatal thyroid function screening. more...

One patient with I-cell disease and three patients with pseudo Hurler polydystrophy as well as their relatives were examined. Activity of acid hydrolases was distinctly elevated in blood plasma of all the patients studied, while in leukocyte extracts it was within the normal limits. The ratio of hexosaminidase A was distinctly decreased in blood plasma of the patient with I-cell disease and of her mother. "Low activity" variant of blood plasma alpha-fucosidase was detected in one patient with pseudo Hurler polydystrophy and in his father. The ratio of bound sialic acids in supernatant and in individual leukocyte fractions was about I in all the patients examined as compared with 0.3-0.5 value in healthy persons. The data obtained suggest an excessive storage of soluble sialyl-containing derivatives in leukocytes of the patients with different variants of I-cell disease. more...

A procedure was developed for estimation of galactocerebroside beta-D-galactosidase activity in leukocytes using a new fluorogenic compound 6-hexadecanoylamino-4-methylum-belliferyl-beta-D-galactop yra noside (HMGal) as a substrate. Some patterns of the fluorometric procedure were compared with corresponding parameters of the spectrophotometric method in which a chromogenic substrate HNGal was used. Sensitivity of the fluorometric procedure with HMGal as a substrate was increased 100-fold as compared with the spectrophotometric method. At the same time, the fluorometric procedure enabled to reduce considerably the incubation period and the cell protein content per an assay. High sensitivity and reproducibility of the procedure with HMGal as a substrate allowed to carry out biochemical diagnosis of Krabbe disease in leukocytes. more...