Selective screening and molecular characteristics of Russian patients with Pompe disease

Introduction. Pompe disease (PD) or type II glycogenosis is a rare multisystem hereditary accumulation disease caused by a deficiency of the enzyme acid maltase (acid alpha-1,4-glucosidase), which leads to reduced activity to the accumulation of glycogen in various organs and tissues of the body. The aim of the study is to develop a high-performance method of early biochemical diagnosis of PD and optimization of its molecular genetic diagnosis. Materials and methods. The characteristics of the relative frequencies and spectrum of the detected mutations were studied using a sample of 7670 patients with suspected Pompe disease admitted to the National Medical Research Center of Children’s Health of the Ministry of Health of Russia as part of the selective screening, as well as eight patients with PD, whose laboratory diagnosis was made outside the framework of this selective screening. Results. As a result of selective screening of PD in Russian patients from high-risk groups, the detectability was 0.47%. PD’s clinical and age characteristics in both children and adults are described. The relative frequencies are calculated, and the spectrum of 47 pathogenic variants of the GAA gene responsible for the occurrence and development of Pompe disease in 44 patients is characterized. Seventeen new mutations of the GAA gene, unknown previously, have been identified and described, adding 2.7% to the HGMD database. Conclusion. Optimization of the algorithm of molecular diagnosis of Pompe disease in Russian patients is proposed.

Clinical and economic justification of screening for mucopolysaccharidosis type I in children at groups of risks

Background. Mucopolysaccharidosis Type I (MPS I) has clinical heterogeneity without specific symptoms leading to difficulties with diagnostic on time. In-depth screening for MPS I in children has aim of early detection and timely treatment with an enzyme replacement therapy. Aim. The purpose of this study was to conduct a clinical and economic assessment of the feasibility of screening for MPS I in children at group of risks. Materials and methods. Model for evaluation of the social-economic burden of MPS I with calculation of expenditures has been created. Costs of diagnosed and non-diagnosed patients in group of risks were identified, including direct medical costs (pharmacotherapy, out-patient cure, hospital admission, complications treatment, hematopoietic stem cell transplantation; direct non-medical (payments for disability); indirect (expenses related to the reduction or loss of the ability to work of one of the parents performing the duties of caring for a disabled child). Results. The weighted average cost per 1 diagnosed patient with mild forms of MPS I with selective screening, was 405,974.22 rubles, which is 184,421.85 rubles less vs average cost per 1 undiagnosed patient. The management and treatment of patients with mild forms of MPS I after selective screening will allow saving up to 17.7 million rubles/year, which would possible to additionally screen 705 patients. Taking into account the size of the population of patients with undiagnosed MPS I, currently the costs for this group amount to 56.7 million rubles, while the «overspend» of budget funds for untimely diagnosis of MPS I for this cohort of children is about 22.6 million rubles/year. Conclusion. Selective screening for MPS I in children at group of risks is economically proved and can lead to treatment on-time for disability and complications prevention.

Intimate relationships among soil bacteria: actinomycetes and mycolic acid-containing bacteria

Co-culture is an efficient strategy for natural product discovery. We have used mycolic acid-containing bacteria (MACB) Tsukamurella pumonis TP-B0596 to induce secondary metabolism by actinomycetes and have found several natural products. We also observed that MACB attached to the mycelium of Streptomyces lividans forming coaggregates during combined-culture. This stimulated interest in the interactions among actinomycetes and MACB, and we found that soil isolated cultures contained a mixture of actinomycetes and MACB. Our previously observed interactions were the result of selective screening and combination of bacteria in the lab, which warranted investigation of the existence of these interactions in the natural soil environment. Therefore, in this paper, we report the interaction between a co-isolated natural pair of actinomycetes and MACB in terms of morphology and metabolic changes. A natural pair of actinomycetes and MACB co-aggregated in liquid culture and showed metabolic changes. Interestingly, co-aggregated actinomycetes and MACB were re-isolated from soil with no obvious morphological colony differences from the colony of a single strain. The results demonstrate that there is a stochastic chance of picking colonies containing co-aggregated actinomycetes and MACB, which suggests that the pair can exist in co-aggregate form in the soil environment and interact with each other.

Universal versus selective screening for gestational diabetes mellitus among antenatal clinic attendees in Abakaliki: using the one-step 75 gram oral glucose tolerance test

Aim To compare universal screening with selective risk factor based screening for GDM, using the one-step 75 g oral glucose tolerance test (OGTT). Materials and method A cross-sectional, comparison between universal and selective risk factor based screening for GDM, among 400 antenatal care clients at Alex-Ekwueme Federal University Teaching Hospital Abakaliki (AE-FUTHA). All the participants had 75 g OGTT at 24–28 weeks of gestation and risk factor screening for GDM. All 400 participants formed the universal group while participants with one or more of the considered risk factors formed the selective risk factor group. Data were analyzed using IBM SPSS version 20. Statistical comparison was done using t- test for continuous variables. Logistics regression was used to determine the level of associations of the independent predictors for hyperglycemia. Level of significance was set at P < 0.05. Results The point prevalence of GDM using universal and selective screening were 11.51 and 7.93% respectively, giving a selective screening miss rate of 31.11%. The sensitivity, specificity, positive predictive value and negative predictive value were 73.58, 48.82, 19.12 and 92.51% respectively for the selective risk factor based screening compared to universal screening. On multivariate analysis; age ≥ 35 years, weight ≥ 90 kg, history of previous GDM and hypertension were significantly related to the development of hyperglycemia. Conclusion Selective risk factor based screening missed 31.11% of patients with GDM when compare to Universal screening with one step 75 g OGTT. Universal screening for GDM using the one step 75 g OGTT is recommended for pregnant women and more studies are needed to compare pregnancy outcomes for pregnant women diagnosed with GDM with and without risk factors.