NGS analysis of collagen type I genes in Polish patients with Osteogenesis imperfecta: a nationwide multicenter study.

Osteogenesis imperfecta (OI) is a rare genetic disorder of the connective tissue. It presents with a wide spectrum of skeletal and extraskeletal features, and ranges in severity from mild to perinatal lethal. The disease is characterized by a heterogeneous genetic background, where approximately 85%-90% of cases have dominantly inherited heterozygous pathogenic variants located in the COL1A1 and COL1A2 genes. This paper presents the results of the first nationwide study, performed on a large cohort of 197 Polish OI patients. Variants were identified using a next-generation sequencing (NGS) custom gene panel and multiplex ligation probe amplification (MLPA) assay. The following OI types were observed: 1 (42%), 2 (3%), 3 (35%), and 4 (20%). Collagen type I pathogenic variants were reported in 108 families. Alterations were observed in α1 and α2 in 70% and 30% of cases, respectively. The presented paper reports 97 distinct causative variants and expands the OI database with 38 novel pathogenic changes. It also enabled the identification of the first glycine-to-tryptophan substitution in the COL1A1 gene and brought new insights into the clinical severity associated with variants localized in "lethal regions". Our results contribute to a better understanding of the clinical and genetic aspects of OI.

Bone Turnover Markers and Bone Mineral Density in Children with Hypophosphatemic Rickets.

Hypophosphatemic rickets is a rare disease that results in bone deformities. However, little is known about bone turnover and bone mass disorders in this disease. This retrospective study included 12 children aged 1-16 years diagnosed with hypophosphatemic rickets. Parameters of calcium-phosphate metabolism and bone turnover markers were analysed. Bone mineral density was assessed with the use of dual-energy X-ray absorptiometry, and indices of quantitative ultrasound examination of tibiae and radial bones were analysed. In the majority of patients, hypophosphatemia and hyperphosphaturia were present. The assessed bone turnover markers showed increased bone formation. Increased pyridinoline levels were found in 5 out of 12 patients. Bone mineral density was decreased only in one patient. Decreased values of quantitative ultrasound examination were observed in all the analysed patients. Conclusions: (1) Bone metabolism disturbances, reflected in the increased values of bone turnover markers and worse bone quality, were found in the group of patients with hypophosphatemic rickets. (2) It is crucial to determine bone turnover markers, dual-energy X-ray absorptiometry findings and indices of quantitative ultrasound examination in order to monitor progress of the disease, as well as treatment effects.

The first glycine-to-tryptophan substitution in the COL1A1 gene identified in a patient with progressively-deforming Osteogenesis imperfecta.

BACKGROUND: Osteogenesis imperfecta (OI) is a genetic disorder of connective tissue with variable phenotype and heterogeneous genetic background. Majority of reported mutations are glycine substitutions, whose clinical outcome ranges from mild to perinatal lethal. The phenotype appears to be influenced by the properties of amino acid side chain and the degree of structural aberration of collagen molecules. Since the genotype-phenotype correlation remains unclear, the severity of mutation is mostly predicted according to previously-reported cases. Although the number of OI variants is constantly expanding, no glycine-to-tryptophan substitutions have been reported in COL1A1 gene. METHODS: A sample from a 15-year-old girl presenting with progressively-deforming OI type III was tested using an NGS custom gene panel. Multiple bioinformatic and interpretation tools, including mutation databases and conservation analysis, were used for variant classification. The presence of the mutation was verified by Sanger sequencing. RESULTS: A novel heterozygous mutation c.733G>T was identified in the COL1A1 gene (p.Gly245Trp). CONCLUSIONS: The discovery of this novel glycine-to-tryptophan substitution located in the COL1A1 gene broadens the spectrum of mutations underlying this rare disease and provides useful information on the clinical outcome of such substitutions.

Novel Mutations Within Collagen Alpha1(I) and Alpha2(I) Ligand-Binding Sites, Broadening the Spectrum of Osteogenesis Imperfecta - Current Insights Into Collagen Type I Lethal Regions.

Osteogenesis imperfecta (OI) is a rare genetic disorder demonstrating considerable phenotypic and genetic heterogeneity. The extensively studied genotype-phenotype correlation is a crucial issue for a reliable counseling, as the disease is recognized at increasingly earlier stages of life, including prenatal period. Based on population studies, clusters in COL1A1 and COL1A2 genes associated with the presence of glycine substitutions leading to fatal outcome have been distinguished and named as "lethal regions." Their localization corresponds to the ligand-binding sites responsible for extracellular interactions of collagen molecules, which could explain high mortality associated with mutations mapping to these regions. Although a number of non-lethal cases have been identified from the variants located in lethal clusters, the mortality rate of mutations has not been updated. An next generation sequencing analysis, using a custom gene panel of known and candidate OI genes, was performed on a group of 166 OI patients and revealed seven individuals with a causative mutations located in the lethal regions. Patients' age, ranging between 3 and 25 years, excluded the expected fatal outcome. The identification of non-lethal cases caused by mutations located in lethal domains prompted us to determine the actual mortality caused by glycine substitutions mapping to lethal clusters and evaluate the distribution of all lethal glycine mutations across collagen type I genes, based on records deposited in the OI Variant Database. Finally, we identified six glycine substitutions located in lethal regions of COL1A1 and COL1A2 genes, of which four are novel. The review of all mutations in the dedicated OI database, revealed 33 distinct glycine substitutions in two lethal domains of COL1A1, 26 of which have been associated with a fatal outcome. Similarly, 109 glycine substitutions have been identified in eight lethal clusters of COL1A2, of which 51 have been associated with a fatal manifestation. An analysis of all glycine substitutions leading to fatal phenotype, showed that their distribution along collagen type I genes is not regular, with 17% (26 out of 154) of mutations reported in COL1A1 and 64% (51 out of 80) in COL1A2 corresponding to localization of the lethal regions.

Metabolic bone markers can be related to preserved insulin secretion in children with newly diagnosed type 1 diabetes.

INTRODUCTION: Type 1 diabetes (T1D) may be associated with numerous complications including bone metabolism disorders. The aim of the study was to evaluate the bone metabolism markers twice in children with a newly diagnosed T1D and after an average of seven months of its duration in relation to parameters of the clinical course of diabetes. MATERIAL AND METHODS: In 100 T1D patients and 52 control subjects, the following bone turnover markers were evaluated: osteocalcin - OC, osteoprotegerin - OPG, sRANKL, and deoxypyridoline in urine - DPD and DXA examination was also performed. RESULTS: Lower OC concentration at T1D onset in comparison to controls (p < 0.001) and its increase during follow-up (p < 0.001) was ob-served. The OPG concentration was elevated at T1D onset as compared to the control group (p = 0.024) and decreased thereafter (p < 0.001). The s-RANKL level increased during follow-up (p < 0.001) and was lower than in controls (p < 0.001). Urine DPD con-centration also increased during follow-up in the T1D patient group (p < 0.001) and was higher in comparison to the control group (p = 0.021). BMD-TBLH was higher in the control group as compared to patients both at T1D onset (p = 0.025) and in follow-up ob-servation (p = 0.034). Moreover, OPG correlated positively with glycated haemoglobin (HbA1c) (p = 0.004) and negatively with fasting C-peptide level (p = 0.046) and BMI Z-score (p = 0.003), whereas s-RANKL correlated positively with both fasting (p < 0.001) and stimulated C-peptide levels (p < 0.001). CONCLUSIONS: Bone metabolism disorders observed at T1D onset in children and modified after reaching the metabolic control of the disease seem to be most strongly associated with preserved insulin secretion.

Evidence of a significant vitamin D deficiency among 9-13-year-old Polish children: results of a multicentre study.

PURPOSE: To evaluate the extent to which the population of Polish preadolescents is vitamin D deficient and to assess seasonal variations in vitamin D status. PARTICIPANTS AND METHODS: A total of 720 healthy children aged 9-13 years (409 girls, 311 boys) residing in 6 representative geographical locations in Poland were studied. A parental-assisted questionnaire provided data on nutritional habits, vitamin D supplements and sun exposure. Serum concentration of 25-hydroxyvitamin was determined twice, after the winter in March and after the summer in October. RESULTS: In March, vitamin D deficiency (25-50 nmol/L) was found in 64%, and severe deficiency (< 25 nmol/L) in 20.2% of children. In October, the deficiency and severe deficiency were still noticed in 25.9 and 0.1% of children, respectively. The mean serum concentration of 25-OHD was 52% higher in October (55.4 ± 14.0 nmol/L) than in March (36.4 ± 13.5 nmol/L), (p < 0.01). In children with 25-OHD < 50 nmol/L in March, their 25-OHD concentration increased by 64% through March to October (32.5 ± 8.2 vs. 53.2 ± 7.9 nmol/L, p < 0.01). An association was found between 25-OHD concentration and regular consumption of vitamin D supplements, cod-liver oil and fish. CONCLUSIONS: The majority of preadolescent Polish boys and girls show vitamin D deficiency after the winter period, although a distinct amelioration over summertime is found in this age group. There is a need to implement effective prevention and intervention strategies in the management of vitamin D deficiency among schoolchildren in Poland, with the supplementation throughout the entire year.

Is it possible to predict a risk of osteoporosis in patients with juvenile idiopathic arthritis? A study of serum levels of bone turnover markers.

BACKGROUND: Low bone mineral density is a common finding in children with systemic connective tissue diseases, including juvenile idiopathic arthritis (JIA). The influence of the ongoing process of bone remodeling on the disease course merits further investigation. The aim of this study was to assess the clinical relevance of markers of bone turnover and their potential role as predictors of higher fracture risk and, by extension, risk of osteoporosis. MATERIALS AND METHODS: Blood samples were collected from 59 patients diagnosed with JIA in order to determine serum levels of the following markers of bone turnover: Beta-Crosslaps, osteocalcin, bone alkaline phosphatase, osteoprotegerin and receptor activator for nuclear factor kappa-B ligand. The values were analyzed with laboratory parameters and results of dual X-ray absorptiometry (DXA). RESULTS: Osteoprotegerin and bone alkaline phosphatase levels were age-dependent. Beta-Crosslaps values were significantly higher in patients with positive JADAS27 score (p=0.0410). Osteoprotegerin levels were higher in patients treated with biological agents than only with disease-modifying anti-rheumatic drugs (p=0.0273). There was no relation between markers of bone turnover and sex, DXA results, dosage of glucocorticosteroids and disease duration. CONCLUSIONS: The authors postulate performing DXA measurements every 6 months in patients with higher disease activity. The potential lower fracture risk in children with JIA within biological treatment needs further assessment. Age- and sex-adjusted reference rates of bone turnover markers need to be developed for Central European patients in order to assess individual values properly.

Vitamin D Supplementation Guidelines for General Population and Groups at Risk of Vitamin D Deficiency in Poland-Recommendations of the Polish Society of Pediatric Endocrinology and Diabetes and the Expert Panel With Participation of National Specialist Consultants and Representatives of Scientific Societies-2018 Update.

INTRODUCTION: Vitamin D deficiency is an important public health problem worldwide. Vitamin D deficiency confers a significant risk for both skeletal and non-skeletal disorders and a number of lifelong negative health outcomes. The objectives of this evidence-based guidelines document are to provide health care professionals in Poland, an updated recommendation for the prevention, diagnosis and treatment of vitamin D deficiency. METHODS: A systematic literature search examining the prevention and treatment strategies for vitamin D deficiency was conducted. Updated recommendations were developed using the Grading of Recommendations, Assessment, Development and Evaluation system describing the strength of the recommendation and the quality of supporting evidence. Twenty-seven contributors representing different areas of expertise and medical specialties, including pediatricians, geriatricians, endocrinologists, epidemiologists, nephrologists, gynecologists and obstetricians evaluated the available published evidence related to vitamin D, formulated the goals of this document and developed a common consolidated position. The consensus group, representing six national specialist consultants and eight Polish and international scientific organizations/societies, participated in the process of grading evidence and drawing up the general and specific recommendations. RESULTS: The updated recommendations define the diagnostic criteria for the evaluation of vitamin D status and describe the prevention and treatment strategies of vitamin D deficiency in the general population and in groups at increased risk of the deficiency. Age- and weight-specific recommendations for prevention, supplementation and treatment of vitamin D deficiency are presented, and detailed practice guidance is discussed regarding the management in primary and specialized health care. CONCLUSION: Vitamin D deficiency remains still highly prevalent in Poland, in all age groups. Currently, there is a great necessity to implement a regular supplementation with recommended doses and to develop an effective strategy to alleviate vitamin D deficiency in the population. These updated recommendations are addressed to health professionals and the authorities pursuing comprehensive health policies and should also be included in public health programs aimed at preventing a broad spectrum of chronic diseases.

[Impact on the development of parental awareness of excess weight in children]. / WpLyw SwiadomoSci rodzicÓw na rozwÓj nadmiaru masy ciaLa u dzieci.

UNLABELLED: A lot of publications emphasize the special role of parents' eating habits and their lifestyle on the prevalence of excess body weight in children. AIM: The aim of this study was to answer the question whether parents of children who are overweight and obese are aware of this problem and what factors affect their perception of the excess body weight degree in their offspring. MATERIALS AND METHODS: The study included 137 children aged 6,5- 13,5 years. 23 respondents were overweight and 76 obese. Compared group consisted of 113 children. All patients underwent physical examination with anthropometric measurements. Parents were asked to complete a questionnaire, where they evaluated the degree of excess body weight of their child. We also asked about both parents' weight and body height, their education and chronic diseases occurring in the family. RESULTS: In the group of obese children 56.2% of the respondents came from families where one parent had excess body weight while 32.9% of them from families where this problem affected both parents. In 51.3% of patients with a body mass index (BMI) above 95 centil, parents wrongly assessed the degree of excess body weight of their child, in overweight group this proportion accounted for 8.7%. There was a statistically significant (p = 0.007) correlation between the degree of children's excess body weight and the ability of parents to estimate that. Parents' education had no influence on the incidence of excess body weight in children and their ability to determine its extent. In the group of obese and overweight children only 4% of parents recognized obesity as a chronic disease. CONCLUSIONS: Parents of children who are overweight and obese have lower awareness about their child's weight in comparison to parents of children with normal weight. There is a statistical correlation between parents' perception of excess body weight and the development of obesity in children.

[Secondary osteoporosisn in boys with Alagille syndrome. Case report].

Alagille syndrome is a multiorgan disorder, which especially manifests itself with cholestasis, characteristic facial features, circulatory systems defects, defects of the front segment of the eye, dysplastic changes in bones and kidneys and impaired angiogenesis.The disease is caused by Jagged 1 gene mutation (JAG, 20p12 chromosome) which encodes ligand for Notch receptor. JAG/ Notch signaling pathway plays important evolutionary role in cell differentiation in organogenesis process . JAG1 expression in numerous tissues leads to multiorganic manifestation. Jagged 1 expression is substantially important for skeleton growth and bone cells activity. Its malfunction may lead to spine and long bones abnormalities, neoplastic changes and osteoporosis. In this case report authors present clinical (long bone fractures) and biochemical manifestations and densitometric abnormalities ( decrease of bone mineral density) in 10 years old boy with Alagille syndrome. Densitometry is suggested to be a good method in early detection of mineralization disturbances in chronic cholestasis and permanent monitoring of changes in bone structure is also very important.

Assessment of the influence of body composition on bone mass in children and adolescents based on a functional analysis of the muscle-bone relationship.

BACKGROUND: The functional model of skeletal development considers the mechanical factor to be the most important skeletal modulant. The aim of the study was a functional analysis of the bone-muscle relationship in children with low and normal bone mass. MATERIAL AND METHODS: The study involved 149 children with low and 99 children with normal bone mass (control group). All patients underwent a densitometry examination (DXA). Low bone mass was diagnosed if the Z-score was below <1.01. Means and standard deviations of parameters required for the functional analysis according to Jaworski and Pludowski were calculated. RESULTS: The study found lower mean values of Z-scores for all parameters in children with low bone mass as compared to the control group. Children with low bone mass had lower content of adipose and muscle tissue and a marked deficit of muscle tissue with regard to height (which according to mechanostat theory leads to lower muscle-generated strain on bones). This group of children had also lower TBBMC/LBM Z-scores, which indicates greater fracture susceptibility. CONCLUSIONS: 1. Functional analysis, which showed associations between bone and muscle tissues, can be useful for diagnosing and monitoring skeletal system disorders as well as making therapeutic decisions.2. The study emphasizes the role of proper nutrition and physical activities, which contribute to proper body composition, in the prevention of bone mineralization disorders in childhood and adolescence. 3. The study showed the inadequacy of the classic reference ranges used in interpreting DXA data in children and demonstrated the usefulness of continuous variables for that purpose.

Immunogenicity of heptavalent conjugate vaccine against Streptococcus pneumoniae in premature babies with low birth weight.

BACKGROUND: There are few studies about immunogenicity and safety of heptavalent pneumococcal-CRM197 conjugate vaccine (PCV7) in low birth weight infants. OBJECTIVE: Assessment of immunogenicity following administration of PCV7 in low birth weight children. METHODS: The PCV7 vaccine was administered to 60 infants divided into two groups: 23 children with birth weight <1000 g (Group I); and 37 children with birth weight ≥1000 g (Group II). Serum was collected four times. RESULTS: Birth weight of children included in the study ranged from 480 g to 2450 g. The primary immunization caused an increase in the average concentration of antibodies for all serotypes in most of the participants, with no significant differences between the groups. However, there were some differences between various serotypes. Group serotypes 6B and 23F were the least immunogenic (≥0.35 µg/mL, Group I vs. Group II - 6B: 78.3% vs. 67,6% p = 0.371 and 23F: 87% vs. 83.8% p = 0.738). Prior to the administration of a booster dose, a significant decrease in antibody titer was observed in all children. The last vaccination resulted in an increased concentration of antibodies in all children in both groups, and the results were significantly higher compared to those measured following administration of three doses of the vaccine. CONCLUSION: PCV7 is immunogenic in children with low, very low, and extremely low birth weight. Serotypes 6B and 23F were the least immunogenic, and serotype 14 proved to be the most immunogenic.

Practical guidelines for the supplementation of vitamin D and the treatment of deficits in Central Europe - recommended vitamin D intakes in the general population and groups at risk of vitamin D deficiency.

INTRODUCTION: Adequate Vitamin D intake and its concentration in serum are important for bone health and calcium-phosphate metabolism as well as for optimal function of many organs and tissues. Documented trends in lifestyle, nutritional habits and physical activity appear to be associated with moderate or severe Vitamin D deficits resulting in health problems. Most epidemiological studies suggest that Vitamin D deficiency is prevalent among Central European populations. Concern about this problem led to the organising of a conference focused on overcoming Vitamin D deficiency. METHODS: After reviewing the epidemiological evidence and relevant literature, a Polish multidisciplinary group formulated theses on recommendations for Vitamin D screening and supplementation in the general population. These theses were subsequently sent to Scientific Committee members of the 'Vitamin D - minimum, maximum, optimum' conference for evaluation based on a ten-point scale.With 550 international attendees, the meeting 'Vitamin D - minimum, maximum, optimum' was held on October 19-20, 2012 in Warsaw(Poland). Most recent scientific evidence of both skeletal and non-skeletal effects of Vitamin D as well as the results of panellists' voting were reviewed and discussed during eight plenary sessions and two workshops. RESULTS: Based on many polemical discussions, including post-conference networking, the key opinion leaders established ranges of serum 25-hydroxyVitamin D concentration indicating Vitamin D deficiency [< 20 ng/mL (< 50 nmol/L)], suboptimal status [20-30 ng/mL(50-75 nmol/L)], and target concentration for optimal Vitamin D effects [30-50 ng/mL (75-125 nmol/L)]. General practical guidelines regarding supplementation and updated recommendations for prophylactic Vitamin D intakes in Central European neonates, infants, children and adolescents as well as in adults (including recommendations for pregnant and breastfeeding women and the elderly) were developed. CONCLUSIONS: Improving the Vitamin D status of children, adolescents, adults and the elderly must be included in the priorities of physicians,healthcare professionals and healthcare regulating bodies. The present paper offers elaborated consensus on supplementation guidance and population strategies for Vitamin D in Central Europe.

Effect of vitamin D receptor gene (VDR) polymorphism on body height in children - own experience.

UNLABELLED: Genetic and environmental factors have an influence on the process of growth and development of the body. One of numerous genetic factors can be the vitamin D receptor gene (VDR). The study aimed at evaluating the relationship between VDR polymorphism and somatic parameters in children. PATIENTS AND METHODS: The study group consisted of 395 children, aged 6-18 years. All the patients underwent gene typing using the PCR-RFLP method within polymorphic loci BsmI (rs1544410), FokI (rs2228570), ApaI (rs7975232) and TaqI (rs731236) of the VDR receptor gene. 294 children made up the control group in the study on the incidence of particular genotypes; in 161 patients somatic measurements of body weight and height were made with standard methods and skeletal densitometry (total body and spine programmes) examination was performed. Statistica 10.0 PL was used for statistical analysis. RESULTS: In patients with low bone mass a relationship between body height and FokI VDR polymorphism was noted. The p-value was statistically significantly different in group I (p=0.002) and borderline significant in group III (p=0.09). None of the polymorphisms of the VDR receptor gene demonstrated any statistically significant differences in anthropometric values in the control group and in children with osteoporosis. SUMMARY: The presence of the F allele of FokI polymorphism of the VDR receptor gene results in increased height, which is best observed in children with low bone mass. The FF genotype favours increased height in the study group of children from Lódz.

Recurrent fractures as a new skeletal problem in the course of Angelman syndrome.

Angelman syndrome is a genetically inherited syndrome with severe retardation of psychomotor development and speech disturbances, usually accompanied by epilepsy, typical dysmorphic features, and some skeletal symptoms. The aim of the current report is to present new skeletal symptoms which may occur in the course of AS, based on a case report of an 8-year-old girl with confirmed 15q11;12 microdeletion and recurrent low-trauma bone fractures. According to our knowledge it is the first report of such skeletal symptoms in patient with a diagnosis of AS.

Assessment of quality of life of parents of children with osteogenesis imperfecta.

OBJECTIVES: The aim of the work was an objective assessment of the quality of life of parents of children with osteogenesis imperfecta (OI) and of its determinant factors. MATERIAL AND METHODS: The survey answers of 25 parents were analyzed and contained demographic parameters, socioeconomic status information, quality of life of responses and type of support they have been receiving. In order to assess the effects of this children's disease on the quality of life of the parents, families were divided into two groups depending on the OI severity: group M--mild (type I and IV OI), group S--severe (type III OI). The objective of the work was carried out based on the WHOQOL-BREF quality of life questionnaire and measures of family status: education degree based on the International Standard Classification of Education (ISCED), a subjective assessment of the family's wealth (Perceived Family Wealth, PFW), and the family's financial resources (Family Affluence Scale, FAS). RESULTS: 56% of respondents assessed their global quality of life (Quality of Life, QL) as good, whereas 8% answered poor. Perception of general health status was similar. Life domains assessed in the WHOQOL-BREF questionnaire received the following mean values on a scale from 4 to 20 points: physical--12.2 +/- 1.2, psychological--15.04 +/- 2.2, environmental--13.32 +/- 2, social relationships--14.28 +/- 1.5. In the severe OI group, the environmental domain was assessed as worse than in the mild OI group and this assessment was statistically significant, despite the fact that the group of families with severe cases of OI received more support from the appropriate institutions. Indicators of socioeconomic status did not affect the respondents' assessment of their global quality of life. CONCLUSIONS: In the tested group of families, the child's disease did not affect either the global quality of life assessment or health of the respondents or their quality of life in terms of physical and mental status and social relationships. The parents of children with severe OI assessed the life domain associated with the environment they live in as worse than the parents of children with mild OI. The global quality of life assessment of the respondents did not depend on the family's socioeconomic status and on the help they have been receiving with regard to care for the child.

[Brittle bone disease type III in neonates--own experience]. / Wrodzona lamliwosc kosci typu III u noworodków--obserwacje wlasne.

UNLABELLED: Fractures of long bone and ribs in the neonatal period may be expression of genetic disturbances of collagen type I production. The aim of the study was to present clinical symptoms, results of radiological, biochemical and densitometric examinations in 11 newborns with osteogenesis imperfecta type III. METHODS: In all children accurate medical history, clinical examination and radiograph were performed. We measured concentration of 25-hydroxyvitamin D (25OHD) and osteocalcin (bone formation marker) in serum. Urinary excretion of bone resorption marker type I collagen N-telopeptide related to creatinine were made. In 5/11 children densitometric examination in Infant programme by DXA method (dual-X-ray absorptiometry) were done. RESULTS: In all family osteogenesis imperfecta occurred by the first. In clinical examination deformities in body proportion, shortness of the extremities, sabre shanks, flabbily of skull bones and reduction of activity were diagnosed. 8/11 newborns had blue sclera. In all X-ray (baby-gram) bone fractures occurring in utero as well as after birth were founded. In biochemical indices a small numbers of abnormality were described. In 5/11 newborns with results of densitometric examination normal bone mineral density adequate to body mass were demonstrated, in 3/5 bone mineral content (BMC) were decreased. CONCLUSION: 1.Osteogens esis imperfecta is the one of reasons of bone fractures in neonates and its diagnosis is based on family history, clinical manifestation and X-ray examination. 2. In newborns with bone fractures dual X-ray absorptiometry are recomendated.

Vitamin D receptor gene variability as a factor influencing bone mineral density in pediatric patients.

To determine the relationship between the polymorphism of vitamin D receptor gene and the bone mineral density in children. The study group consisted of 395 children aged 6-18 years. All patients underwent genotyping using the PCR-RFLP method within polymorphic loci BsmI (rs1544410), FokI (rs2228570), ApaI (rs7975232) and Taq I (rs731236) of the VDR gene. The BMD (g/cm(2), Z score) and BMC (g, Z score) by DXA method, as well as Z scores of the BUA, SOS and Stiffness ultrasound parameters were evaluated. Based on densitometry results, children were divided into 3 groups: I-Z score ± 1.0; II-Z score from -1.1 to -2.0; and III-Z score ≤ -2.1. A control group numbering 294 children was used for the purpose of allele frequency comparisons. The occurrence of studied polymorphism alleles in the control group did not significantly differ from the values expected according to the Hardy-Weinberg equilibrium (p values: 0.1224 for BsmI; 0.5958 for TaqI; 0.0817 for ApaI; and 0.8901 for FokI). Allele a ApaI carrier status in group III children was associated with an increased BMD (x = 0.8 vs 0.69, p = 0.0296) and BMC value (x = 28.76 vs 22.14, p = 0.0565) in spine projection results, Stiffness (x = -1.12 vs -1.91, p = 0.0347) and SOS (x = -1.43 vs -2.27, p = 0.0319) ultrasound parameters. In group II, significantly increased SOS values (-1.13 vs -1.73, p = 0.0378) were noted in f (FokI) carriers. The presence of aa ApaI and ff FokI polymorphisms favours a higher bone mass and better bone structure (decreased bone mass loss) in the analysed group.

Proteomic analysis of plasma profiles in children with recurrent bone fractures.

UNLABELLED: The aim of the study is proteomic analysis of the plasma profile in children with recurrent bone fractures. The study involved 16 children: 6 patients with recurrent low-energy fractures and normal bone mass and 10 with osteogenesis imperfecta. In the analysis of the protein profile, the two-dimensional protein electrophoresis was used (Ettan DALT II, Amersham Bioscience). The images of protein gels were compared with controls. The protein spots with changed expression were cut from the gel and the amino acid sequence was analyzed with the mass spectrometry method (Q-Tof Premier(TM) API MASS SPECTROMETR, Waters) for protein identification. The most prevalent protein with changed expression, with respect to controls, was haptoglobin observed in 6 patients with a severe form of osteogenesis imperfecta. Increased haptoglobin concentration in these patients was confirmed by the ELISA method. Peptides corresponding to alpha-1 acid glycoprotein and serum amyloid P-component, apolipoprotein A-I, and transthyretin were detected in one, two and three children, respectively. CONCLUSIONS: 1) The results show increased haptoglobin which may be suggestive of an inflammatory component taking part in the course of osteogenesis imperfecta. 2) Further studies to explain the possible relationship of this protein with increased bone fragility are necessary.

Immunogenicity and safety of heptavalent conjugate vaccine against Streptococcus pneumoniae in pre-term Polish infants.

The purpose of the study was to assess post-vaccination immune response and occurrence of adverse events in the group of prematurely born infants. The study included 40 pre-term infants. Each child was vaccined four times (2, 4, 6 and 16 months) with the heptavalent conjugated pneumococcal vaccine (PCV7). Assessing of the level of antibodies was performed before vaccination, 4 weeks after primary series, before and 4 weeks after the booster dose. The research participants were qualified into 2 groups: group I - 19 children born before 30th gestational week, group II - 21 children born between the 30th and 34th gestational week. After the basic vaccination, an increase in the average antibody concentration in the area of all serotypes in most of the children tested was registered, with no significant differences observed between the groups. However, differences between individual serotypes were observed. The lowest values were found for serotype 6B. Before administering the booster dose, a significant drop in antibody titre in all of the children tested was noted. The last vaccination caused another significant increase in antibody concentration in both groups and the results obtained were markedly higher than those obtained after administering three vaccine doses. The majority of the children tested (with the exception of three from group II) achieved the preventive antibody level ≥ 0.35 µg/ml. In all of the children, no serious adverse events were observed. Our research showed, that heptavalent pneumococcal conjugate vaccine is immunogenic in children born before the completion of the 34th week of pregnancy. A booster dose of vaccine must be given at the right time to optimal response to the vaccine for all serotypes. Finally, any serious adverse events were observed.