Molecular genetics of PKU in Poland and potential impact of mutations on BH4 responsiveness

Tetrahydrobiopterin (BH4) has been recently approved as a treatment of patients with phenylketonuria. However, as a confirmation of BH4-responsiveness, it might require a very expensive trial treatment with BH4 or prolonged BH4-loading procedures. The selection of patients eligible for BH4-therapy by means of genotyping of the PAH gene mutations may be recommended as a complementary approach. A population-wide genotyping study was carried out in 1286 Polish phenyloketonuria-patients. The aim was to estimate the BH4 demand and to cover prospectively the treatment by a National Health Fund. A total of 95 types of mutations were identified. Genetic variants corresponding with probable BH4-responsiveness were found in 28.2% of cases. However, patients with mild or classical phenylketonuria who require continuous treatment accounted for 11.4% of the studied population only. Analysis of the published data shows similar percentage of the "BH4-responsive" variants of a PAH gene in patients from other countries of Eastern Europe. Therefore, it can be concluded, that the proportion of phenylketonuria-patients who could benefit from the use of BH4 reaches approximately 10% in the entire region

Comparison of Mechanical and Barrier Properties of Al2O3/TiO2/ZrO2 Layers in Oxide-Hydroxyapatite Sandwich Composite Coatings Deposited by Sol-Gel Method on Ti6Al7Nb Alloy

In this study, coatings of different oxides (TiO2, Al2O3, ZrO2) and hydroxyapatite (HAp) as well as sandwich composite hydroxyapatite with an oxides sublayer (oxide+HAp) were deposited on Ti6Al7Nb alloy using the sol-gel dip-coating method. The coatings were characterized in terms of morphology (optical microscope), surface topography (AFM), thickness (ellipsometry), and crystal structure (XRD/GIXRD). The mechanical properties of the coatings-hardness, Young's modulus, and adhesion to the substrate-were examined using nanoindentation and scratch tests. The barrier properties of the coatings against the migration of aluminum ions were examined by measuring their concentration after soaking in Hank's balanced salt solution (HBSS) with the use of optical emission spectrometry of inductively coupled plasma (ICPOES). It was found that all the oxide and HAp coatings reduced the permeation of Al ions from the Ti6Al7Nb alloy substrate. The best features revealed an Al2O3 layer that had excellent barrier properties and the best adhesion to the substrate. Al2O3 as a sublayer significantly improved the properties of the sandwich composite HAp coating