[Open, non-comparative phase III clinical study to evaluate the efficacy and safety of sapropterin in patients with phenylketonuria and hyperphenylalaninemia].

BACKGROUND: Phenylketonuria (PKU) is an autosomal recessive inherited disease associated with impaired metabolism of the amino acids phenylalanine (Phe) and tyrosine. The main criterion for diagnosis of PKU is high blood Phe level determined during neonatal screening. In case where PKU patient is responsive to tetrahydrobiopterin treatment, sapropterin restores the impaired activity of the enzyme phenylalanine hydroxylase, resulting in the stimulation of normal Phe metabolism and thereby enhancing patient tolerance to natural products. AIM: The present open, non-comparative clinical study was initiated to assess the degree and frequency of response after 8-day sapropterin administration and assess the safety of 6-week sapropterin treatment in patients with PKU and hyperphenylalaninemia. PATIENTS AND METHODS: The study enrolled 90 patients with PKU. The criterion of response to 8-day sapropterin therapy was the reduction of Phe blood levels ≥ 30% compared with the baseline value. RESULTS: Positive response to treatment was observed in 30 (33.3%) patients (95% CI 23.7-44.1). The mean percentage change in Phe blood levels after the 8-day response test period compared to Phe levels prior to dosing was 14.1 ± 28.4% in the overall subject population (95% CI 8.2-20.1) and 44.3 ± 15.1% in the subpopulation of patients with a positive response (95% CI 38.6-49.9). During the study, adverse events were reported in 24 (26.7%) patients in the overall population in 16 (53.3%) patients in the subpopulation who had a response. CONCLUSION: The study results confirmed the efficacy and safety of sapropterin therapy in patients with PKU, which is consistent with international clinical trials data.

[Prevalence of hereditary pathology in Altai Republic]. / Rasprostranennost' nasledsvennoi patologii u naseleniia respubliki Altai.

Medical genetic study of the population of Altai Republic (Russia) has been performed. The population sample comprises 203 148 subjects, including 59 196 Altaians, 134 972 Russians, and 8980 Kazakhs. For each nosological group, the loads of Mendelian pathology with different modes of inheritance and their prevalence rates in urban and rural populations have been determined. Thirty-six autosomal dominant (AD) diseases have been found in a total of 121 subjects, with hereditary syndromes being the most prevalent. Autosomal recessive (AR) pathology is represented by 24 diseases found in 158 subjects, with metabolic disorders being the most prevalent; and X-linked pathology, by four diseases in nine subjects. The prevalence rate has been calculated for each nosological form in the district where it has been found. The loads of AD, AR, and X-linked pathologies in the urban population were, respectively, 2.98 and 9.62 per 1000 people and 0.56 per 1000 men in Altaians; 0.86 and 0.94 per 1000 people and 0.23 per 1000 men in Russians; 0.34 and 1.16 per 1000 people in Kazakhs. In the rural population, the genetic load has been calculated for each district. The spectrum of hereditary pathology in the populations studied is described.

[Analysis of the association between the T113M polymorphism of the human il-9 gene and bronchial asthma]. / Otsenka assotsiatsii polimorfizma T113M gena IL9 s bronkhial'noi astmoi.

The T113M polymorphism resulting from the missense mutation in exon 5 of the human interleukin 9 (IL9) gene was tested for association with bronchial asthma (BA). The genotype frequency analysis did not reveal a deviation from the Hardy-Weinberg equilibrium. A comparison of the genotype frequency distributions in a control group of healthy individuals and in patients with BA suggested an association between T113M and the clinical phenotype. However, this association was not confirmed by the affected family-based association control (AFBAC) or the transmission/disequilibrium test (TDT).

[Dynamics of the marital structure with respect to the nationality and birthplace of spouses in a modern urbanized Siberian population (as exemplified by Tomsk)]. / Dinamika struktury brakov po natsional'nosti i mestam rozhdeniia suprugov v sovremennoi urbanizirovannoi sibirskoi populiatsii (na primere g. Tomska).

To analyze a population's marital structure with respect to the ethnicity and birthplace of the spouses and to estimate the indices of endogamy, migration, and marriage assortativeness, the records of marriages in Tomsk during two periods of time (1970-1972 and 1985-1990) were studied. The parameters of the population-genetic and demographic structure proved to change during the studied period: the endogamy index and the indices of marriage assortativeness increased, and the migration index decreased. These data suggest that the genetic structure of the Tomsk urbanized population stabilized with time and that the intrapopulation subdivision decreased (a tendency for panmixia).

[Genetic-demographic characteristics of farming regions and small cities of the Tomsk district]. / Genetiko-demograficheskaia kharakteristika sel'skikh raionov i malykh gorodov Tomskoi oblasti.

In nine of the sixteen rural regions and three small towns in Tomskaya oblast, marriage structure with regard to birth place and ethnicity of spouses was genetically and demographically studied by selectively analyzing marriage records from 1970-1985. Migration processes of high intensity were shown to be characteristic of rural and urban inhabitants of Tomskaya oblast. High values of the migration index (0.56 for rural regions and 0.75 for small towns) and low values of the local endogamy index (0.22 and 0.08 respectively) were obtained. Analysis of marriage assortativeness according to birth place and ethnicity of spouses demonstrated, in total, low but statistically significant estimates of marriage assortativeness. Subdivision of oblast populations was determined mainly by ethnicity.