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Early detection and therapy of haematological abnormalities and/or diseases may improve the prognosis of metabolic disorders. Accordingly, we aimed to evaluate the frequency and types of haematological abnormalities in children[-31pc] with various inherited metabolic disorders. The study group comprised 46 children with metabolic disorders who were followed at the Pediatric Metabolism Unit and were referred to the Pediatric Hematology Unit for evaluation of anaemia between June 2000 and 2005. The mean age of the children was 55.2 +/- 64.8 months at haematological evaluation (range 1 month-18 years, median 22.0 months); 16 were female and 30 were male. Of these 46 patients with anaemia, 25 of (54.3%) had anaemia of chronic disease (ACD), 9 (19.6%) had iron-deficiency anaemia (IDA), 7 (15.2%) had megaloblastic anaemia due to vitamin B(12) deficiency, 3 (6.5%) had chronic haemolytic anaemia, 2 (4.3%) had autoimmune haemolytic anaemia, 1 had beta-thalassaemia major, and 1 had hereditary spherocytosis. In addition to the anaemia, bicytopenia or pancytopenia was found in 8 of 46 children (17.4%). The study indicated that in organic acidaemias including methylmalonic acidaemia, propionic acidaemia, isovaleric acidaemia, and argininosuccinic acidaemia, the majority of patients had ACD (75%), which was followed by vitamin B(12) deficiency anaemia and IDA (p0.001). In PKU, both nutritional anaemias and ACD were present at about same frequency: 46.7% and 40%, respectively (p0.05). This study suggested that congenital anaemias such as hereditary spherocytosis or thalassaemias should be kept in mind as a coexisting haematological diseases in young patients with inborn errors of metabolism. In conclusion, ACD and nutritional anaemias are the most prevalent anaemias seen in patients with inborn errors of metabolism. Early detection of the disease, early administration of specific diet, and close monitoring of the patients are very important factors to prevent the development of haematological diseases in patients with inborn errors of metabolism.

The surface profile of a rough object is obtained by white light interferometry. The real and noisy simulated correlograms are analysed by using sliding average, continuous wavelet transform and a new algorithm that is called the continuous wavelet transform phase method. Measurement repeatability is calculated for each algorithm and it has been shown that the continuous wavelet transform phase method gives a smaller peak to valley value and standard deviation than other methods. Hence, this algorithm can be used to obtain a good repeatability or standard deviation in white light interferometry.

3D profile measurement of an object is studied experimentally by using a standard fringe projection technique consisting of a CCD camera and a digital projector. The height profile of the object is calculated through the phase change distribution of the projected fringes from the phase and phase gradient of the wavelet transform. Experimental results for the Fourier transform profilometry algorithm are compared with the results of wavelet analysis.

We studied the incidence of late-onset congenital adrenal hyperplasia (LOCAH) due to 2l-hydroxylase (21-OH) deficiency, its molecular genotype expression, and its association with the major histocompatibility complex in 61 women with hirsutism and polycystic ovary. Ultrasound, clinical and hormonal parameters were used to define polycystic ovary syndrome (PCOS). Baseline and ACTH stimulated 17alpha-hydroxyprogesterone (17-OHP) levels were measured for screening of LOCAH during follicular phase. Forty-one women were diagnosed as having PCOS (67%) and 20 women were diagnosed as having had LOCAH due to 2l-OH deficiency (33%). In LOCAH patients, the most common mutation (Val281-Leu, V281L) was found in 10 patients (7 heterozygous/3 homozygous). The frequency of V281L mutation was found as 32.5% in 20 patients. All patients with the V281L mutation presented HLA-B14 (100%) and six of them presented DR1 (60%), confirming that LOCAH is linked to the histocompatibility complex. Although molecular analysis is a better and more accurate means for an exact and precise definition of LOCAH, it is not routinely available in our country. So, ACTH stimulation test combined with HLA-B14 typing should be more widely utilized in these patients. As a result, LOCAH due to 21-OH deficiency is unexpectedly high in Turkish patients with hirsutism and PCO.

Strict control of hyperphenylalaninemia is necessary in pregnant women with phenylketonuria (PKU) in order to prevent phenylalanine embryopathy in the fetus, characterized by intrauterine growth restriction, dysmorphic facies, congenital heart disease, microcephaly and intellectual disability, collectively known as maternal PKU syndrome. Sapropterin dihydrochloride (SD), an alternative or adjunct to dietary therapy in patients with tetrahydrobiopterin (BH4)-responsive PKU, has recently been used in several cases to treat PKU during pregnancy with satisfactory results. Here, we report two pregnancies treated with SD and unrestricted diet in a patient with BH4-responsive mild PKU. The first pregnancy resulted in a partial hydatidiform mole and was terminated, whereas a healthy infant was born from the second pregnancy. Phenylalanine control was optimal in both pregnancies. To the best of our knowledge, this is the first report on the development of partial hydatidiform mole associated with SD treatment and the second report on molar pregnancy in PKU. While the relation between SD and molar pregnancy is unknown, further studies may be needed to investigate the possible effects of SD on fertilization.

Classical citrullinemia (CTLN1), a rare autosomal recessive disorder, is caused by mutations of the argininosuccinate synthetase (ASS) gene, localized on chromosome 9q34.1. ASS functions as a rate-limiting enzyme in the urea cycle. Previously, we identified 32 mutations in the ASS gene of CTLN1 patients mainly in Japan and the United States, and to date 34 different mutations have been described in 50 families worldwide. In the present study, we report ASS mutations detected in 35 additional CTLN1 families from 11 countries. By analyzing the entire coding sequence and the intron-exon boundaries of the ASS gene using RT-PCR and/or genomic DNA-PCR, we have identified 16 novel mutations (two different 1-bp deletions, a 67-bp insertion, and 13 missense) and have detected 12 known mutations. Altogether, 50 different mutations (seven deletion, three splice site, one duplication, two nonsense, and 37 missense) in 85 CTLN1 families were identified. On the basis of primary sequence comparisons with the crystal structure of E. coli ASS protein, it may be concluded that any of the 37 missense mutations found at 30 different positions led to structural and functional impairments of the human ASS protein. It has been found that three mutations are particularly frequent: IVS6-2A>G in 23 families (Japan: 20 and Korea: three), G390R in 18 families (Turkey: six, U.S.: five, Spain: three, Israel: one, Austria: one, Canada: one, and Bolivia: one), and R304W in 10 families (Japan: nine and Turkey: one). Most mutations of the ASS gene are "private" and are distributed throughout the gene, except for exons 5 and 12-14. It seems that the clinical course of the patients with truncated mutations or the G390R mutation is early-onset/severe. The phenotype of the patients with certain missense mutations (G362V or W179R) is more late-onset/mild. Eight patients with R86H, A118T, R265H, or K310R mutations were adult/late-onset and four of them showed severe symptoms during pregnancy or postpartum. However, it is still difficult to prove the genotype-phenotype correlation, because many patients were compound heterozygotes (with two different mutations), lived in different environments at the time of diagnosis, and/or had several treatment regimes or various knowledge of the disease.

Arslan, Mustafa/0000-0003-4882-5063; DURSUN, ALI DOGAN/0000-0001-9056-0025 WOS: 000340863400004 PubMed: 25077362 Purpose: The aim of this study was to investigate the effects of iloprost (I) on lung injury as a remote organ following skeletal muscle ischemia-reperfusion injury in a rat model. Materials and methods: Twenty-four Wistar Albino rats were randomized into four groups (n = 6). Laparotomy was performed in all groups under general anesthesia. Only laparotomy was applied in Group S (Sham). Ischemia reperfusion group (Group I/R) underwent ischemia and reperfusion performed by clamping and declamping of the infrarenal abdominal aorta for 120 minutes. Group iloprost (Group 1) received intravenous infusion of iloprost 0.5 ng/kg/min, without ischemia and reperfusion. Group I/R/I received intravenous infusion of iloprost 0.5 ng/kg/min immediately after 2 hours of ischemia. At the end of the study, lung tissue was obtained for determining total oxidant status (TOS) and total antioxidant status (TAS) levels, histochemical and immunohistochemical determination. Results: Diffuse lymphocyte infiltration was detected in immunohistochemical examination of lung tissue in Group I/R. The connective tissue around bronchi, bronchioles and vessel walls was found to be increased. Although minimal local lymphocyte infiltration was detected in some fields in Group I/R/I, the overall tissue was found to be similar to Group S. iNOS expression was significantly higher in Group I/R, when compared with Group S and significantly lower in Group I/R/I compared to Group I/R. TOS levels were significantly higher in Group I/R, when compared with groups S and I (p = 0.028, p = 0.016, respectively) and significantly lower in group I/R/I, when compared with Group I/R (p = 0.048). TAS levels were significantly higher in Group I/R, when compared with groups S, I (p = 0.014, p = 0.027, respectively) and significantly lower in Group I/R/I, when compared with Group I/R (p = 0.032). Conclusion: These results indicate that administration of iloprost may have protective effects against ischemia reperfusion injury (Fig. 8, Tab. 1, Ref. 30). Text in PDF www.elis.sk.

Methylmalonic aciduria and homocystinuria, cobalamin C (cblC) type, is the most frequent inborn error of vitamin B12metabolism. The clinical phenotype includes systemic symptoms and neurological decompensation. Affected patients can be divided into two broad groups, as early-onset and late-onset. We present a Turkish patient who had neurological impairment at the age of four years as presented with late-onset cblC defect. Homozygous c.394CT; p.R132* mutation in the MMACHC gene was detected. The patient was treated with hydroxocobalamin, betaine and folic acid combination with good clinical and biochemical response.

WOS: 000343331200010, PubMed: 25220015, We aim to investigate the genetic basis of isovaleryl-CoA dehydrogenase (IVD) gene mutations and genotype-phenotype correlations in Turkish patients. Accordingly, bi-directional sequencing was performed to screen 26 patients with isovaleric acidemia (IVA). Nine novels (c.145delC, c.234 + 3G > C, c.506_507insT, p.Glu85Gln, p.Met147Val, p.Ala268Val, p.Ile287Met, p.Gly346Asp and p.Arg382Trp) and six previously reported (c.456 + 2T > C, p.Arg21His, p.Arg21Pro, p.Arg363Cys, p.Arg363His p.Glu379Lys) pathogenic mutations were identified. Pathogenicity of the novel mutations was supported using computational programs. No clear genotype-phenotype correlation could be determined. One of the cases with the novel c.234 + 3G > C mutation has portoseptal liver fibrosis, the clinical condition that was first reported for IVA. This study is the first comprehensive report from Turkey related to IVA genetics that provides information about the high number of disease-causing novel mutations. (C) 2014 Elsevier Masson SAS. All rights reserved., [DPT-1206400603]; [TUBITAK-111S217], This study was funded by the DPT-1206400603 and TUBITAK-111S217 projects.

Dursun syndrome is a triad of familial primary pulmonary hypertension, leucopenia, and atrial septal defect. Here we demonstrate that mutations in G6PC3 cause Dursun syndrome. Mutations in G6PC3 are known to also cause severe congenital neutropenia type 4. Identification of the genetic basis of Dursun syndrome expands the pre-existing knowledge about the phenotypic effects of mutations in G6PC3. We propose that Dursun syndrome should now be considered as a subset of severe congenital neutropenia type 4 with pulmonary hypertension as an important clinical feature.

To the Editor, Alangari et al. reported four patients with cyclic neutropenia (CyN) due to G6PC3 genemutation (c.974 T>G, p.Leu325Arg). In the article, four patients presented clearly with CyN associated with thrombocytopenia [1]. They concluded that their cases were the first report of a homozygous mutation inG6PC3 resulting in a phenotype compatible with CyN in addition to the classical phenotype of Severe Congenital Neutropenia (SCN) [1]. We would like to draw attention to the gradually widening clinical spectrum and allelic heterogeneity due to G6PC3 gene defects. G6PC3 gene defect results in three major clinical spectra; Dursun syndrome (OMIM 613034 and 612541), syndromic severe congenital neutropenia 4 (SCN4), and nonsyndromic SCN4 [2–5]. Major findings of Dursun syndrome are primary pulmonary hypertension (PPH) developed in newborn period which is one of the most remarkable finding differentiating it from other types of SCN4, secundum type ASD, in addition to neutropenia, thrombocytopenia, anemia, monocytosis all of which show a fluctuating pattern, dysplasia in all cell lines in bone marrow, and hypoplasia of the thymus associated with severe lymphopenia. Minor findings of the syndrome are proximal localization of the first phalanx, completeincomplete simian line, broad nasal bridge, undescended testis, pectus carinatum and high palatal arch. Themutation in the original cases with Dursun syndrome was c.346A>G; p.Met116Val [3]. Until now, 57 cases due toG6PC3 deficiency have been reported and only two of them are siblings with Dursun syndrome. It seems that the similarities in CyN/SCN and Dursun syndrome might be attributable to the G6PC3 mutations and the least partly, the differences can be explained by modifiers and residual enzyme activity. Recently two new patients with different sex were diagnosed in our department who mainly presented cyclic neutropenia and pulmonary hypertension developed in newborn period. These two patients also presented minor findings of Dursun syndrome such as proximal localization of thumb, simian line, broad nasal bridge, and undescended testis in the male patient. In these newly diagnosed patients, mutation screening for G6PC3 gene revealed two different homozygousmutations respectively, c.765_766delAG; p.Ala257fs [6] and c.175T>C; p.Trp59Arg (manuscript in preparation). In our original article [2], we especially emphasized cyclic pattern of neutropenia every one or twoweeks. In addition, we would like to take attention that other blood cell lines including lymphocyte, monocyte, and thrombocyte have similar fluctuating pattern. The newest two patients with Dursun syndrome also clearly presented a fluctuating pattern in neutropenia similar to original cases every one or two weeks. In a conclusion, clinical symptoms in G6PC3 deficiency are gradually expanding, however, care should be taken when considering the “new” symptoms, whether they can be attributed to G6PC3 deficiency primarily or they simply appear secondary to complications of the disorder. In addition, we would like to stress that rare diseases such as Dursun syndrome are quite valuable to improve our understanding of disease mechanisms as well as interaction of different biochemical pathways.

In many countries, neonatal screening programs have been unable to expand and have been limited to a few diseases. We highlight herein the opportunity available for the early detection of some inborn errors of metabolism (IEMs) in those countries in which newborn screening programs are limited. All the newborns that are referred to us for hyperphenylalaninemia are examined physically and their blood samples are checked by both high-performance liquid chromatography (HPLC) for blood phenylalanine levels and by amino acid analyzer for the measurement of blood amino acid concentrations. Seven patients who had been referred to our unit for hyperphenylalaninemia were eventually diagnosed with another IEM. A careful physical examination of the babies sent for positive screening test result combined with the utilization of low expense screening techniques at the experienced referring centers might facilitate otherwise missed opportunities for the early detection of some IEMs.

Lysinuric protein intolerance is an autosomal recessive metabolic disorder caused by defective transport of the cationic amino acids lysine, arginine and ornithine in the epithelial cells of the basolateral membrane in the small intestine and renal tubules. Mutations in the solute carrier family 7, member 7, SLC7A7, gene cause this multisystemic disease with a variety of clinical symptoms such as hepatosplenomegaly, osteoporosis, hypotonia, developmental delay, pulmonary insufficiency or end-stage renal disease. In the present study, genomic structure of SLC7A7 in six Turkish patients with lysinuric protein intolerance was examined in order to detect disease causing mutations by denaturing high pressure liquid chromatography and direct sequencing. Four novel mutations were identified in SLC7A7: c.223insGTC, p.Val74_Ile75insVal; c.283insTGG, p.Glu94_Thr95insTrp; c.344_347delTTGC, p.Leu115LeufsX53; and c.1099insT, p.Ile367TyrfsX16. Clinical and biochemical findings were evaluated together with these molecular analyses.

Faruk Metin Çomu,1 Yiğit Kılıç,2 Abdullah Özer,2 Mehmet Kirişçi,3 Ali Doğan Dursun,4 Tolga Tatar,2 Mustafa Hakan Zor,2 Hakan Kartal,2 Ayşegül Küçük,5 Hakan Boyunağa,6 Mustafa Arslan71Department of Physiology, Kirikkale University Medical Faculty, Kirikkale, 2Department of Cardiovascular Surgery, Gazi University Medical Faculty, Ankara, 3Department of Cardiovascular Surgery, Necip Fazil State Hospital, Kahramanmaras, 4Department of Physiology, Ankara University Medical Faculty, Ankara, 5Department of Physiology, Dumlupinar University Medical Faculty, Kütahya, 6Department of Biochemistry, Kirikkale University Medical Faculty, Kirikkale, 7Department of Anaesthesiology and Reanimation, Gazi University Medical Faculty, Ankara, TurkeyBackground: Ischemia reperfusion injury (I/R) in hind limb is a frequent and important clinical phenomenon. Many structural and functional damages are observed in cells and tissues in these kinds of injuries. In this study, we aimed to evaluate the effect of picroside II on lipid peroxidation and erythrocyte deformability during I/R in rats.Methods: Rats were randomly divided into four groups – each containing six animals (sham, I/R, sham + picroside II, and I/R + picroside II). The infrarenal section of the abdominal aorta was occluded with an atraumatic microvascular clamp in I/R groups. The clamp was removed after 120minutes and reperfusion was provided for a further 120 minutes. Picroside II (10 mg·kg-1) was administered intraperitoneally to the animals in the appropriate groups (sham + picroside II, I/R + picroside II groups). All rats were euthanized by intraperitoneal administration of ketamine (100 mg·kg-1) and taking blood from the abdominal aorta. Erythrocytes were extracted from heparinized complete blood samples. Buffer (PT) and then erythrocytes (PE) were passed through the filtration system and the changes in pressure were measured to investigate the role of serum malondialdehyde and nitric oxide (NO) in lipid peroxidation and erythrocyte deformability index.Results: Deformability index was significantly increased in the I/R group compared to groups sham, sham + picroside-II, and I/R + picroside-II (P

We have investigated seven patients with the type B form of pyruvate carboxylase (PC) deficiency. Mutation analysis revealed eight mutations, all novel. In a patient with exon skipping on cDNA analysis, we identified a homozygous mutation located in a potential branch point sequence, the first possible branch point mutation in PC. Two patients were homozygous for missense mutations (with normal protein amounts on western blot analysis), and two patients were homozygous for nonsense mutations. In addition, a duplication of one base pair was found in a patient who also harboured a splice site mutation. Another splice site mutation led to the activation of a cryptic splice site, shown by cDNA analysis.All patients reported until now with at least one missense mutation have had the milder type A form of PC deficiency. We thus report for the first time two patients with homozygous missense mutations with the severe type B deficiency, clinically indistinguishable from other patients with type B form of PC deficiency.The mutations found here are novel; it is noteworthy that four Turkish patients did not have any mutations in common, despite the rarity of PC deficiency. There is thus no evidence for recurrent mutations in the Turkish or other populations.

Acrodermatitis enteropathica (AE) is a rare autosomal recessive disorder of zinc deficiency due to an abnormal intestinal zinc transporter. It is characterized by the triad of acral dermatitis, alopecia, and diarrhoea. Once AE is correctly diagnosed, patients are treated with orally administered zinc sulphate. In some patients, relapses occur during adolescence, despite the regular treatment. Here, we discuss the clinical and molecular features of a 13-year-old adolescent girl with acrodermatitis enteropathica who was resistant to high-dose zinc sulphate therapy. We successfully treated the patient with zinc gluconate and vitamin C, and we detected a novel homozygous c.541_551dup (p.Leu186fsX38) mutation in the exon 3 of her SLC39A4 gene.

OBJECTIVE Hypoxia-inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) are involved in signaling mechanisms of cellular responses to hypoxia. These factors have been investigated in tissue samples by simulating different altitudes by changing the percentage of oxygen. We aimed first to evaluate the effect of normobaric, systemic hypoxia (11% O2) on HIF-1α and VEGF mRNA levels in the heart muscle; secondly, to compare the levels of HIF-1α and VEGF mRNA in the left and right ventricle muscles. METHODS In this experimental study, 33 New Zealand male rabbits were assigned to control, acute hypoxia (4 hours) and intermittent hypoxia (4 hours/day for 14 days) groups (n=11/group). Total RNA was isolated from right and left ventricles of the heart. The expressions of HIF-1α and VEGF mRNAs were investigated by using Reverse Transcription Polymerase Chain Reaction (RT-PCR) method. The obtained data were compared by using ANOVA and paired t-test. RESULTS The results indicated that left ventricle VEGF mRNA expressions in both acute and intermittent hypoxia groups (1.08 ± 0.15 and 1.03 ± 0.19, respectively) were higher than that in the control group (0.88 ± 0.15) (p=0.03). Hypoxia treatments did not significantly alter HIF-1α mRNA in both ventricles (p=0.60 and p=0.51 for left and right ventricles, respectively). CONCLUSION Since systemic hypoxia results in induction of VEGF mRNA up-regulation only in left ventricle, it could be related to its higher metabolic activity and oxygen utilization. Hypoxia induced changes in the expression of HIF-1α mRNA may not be the only determining factor for HIF-1/VEGF pathway induction or the observed VEGF induction could be through other hypoxia sensitive pathways.

Deoxyguanosine kinase (DGUOK) catalyzes the first step of the mitochondrial deoxypurine salvage pathway, the phosphorylation of purine deoxyribonucleosides. Mutations in the DGUOK gene have been linked to inherited mitochondrial (mt)DNA depletion syndromes, neonatal liver failure, nystagmus, and hypotonia. We now report a novel homozygous c.34CT (p.Arg12X) mutation found in an affected newborn of asymptomatic consanguineous parents. Respiratory distress started in the first hours after birth. The patient died at the age of 42 days due to liver failure. This genotype, which is to be expected for a homozygous stop codon mutation in exon 1, is associated with a severe clinical presentation.

This paper presents the simulation of a vane-type magnetron using the commercial electromagnetic software Particle-in-Cell (PIC) solver in CST. The magnetron mainly consist of 18 anode vanes without strap. The resonance frequency has been selected in X band since it has a long production history enabling a ready comparison of computed and measured results. Simulation of magnetrons has been improved by changing dimensions of cavities, optimizing voltage and applied magnetic fields values. The aim of this work is to tune the operation frequency of magnetron under the constant electric field and the magnetic field between the anode and cathode. © 2011 IEEE. 2011 30th URSI General Assembly and Scientific Symposium, URSIGASS 2011 -- 13 August 2011 through 20 August 2011 -- Istanbul -- 87252

Primary systemic carnitine deficiency (SCD) is an autosomal recessive disorder caused by defective cellular carnitine transport. Patients usually present with predominant metabolic or cardiac manifestations. SCD is caused by mutations in the organic cation/carnitine transporter OCTN2 (SLC22A5) gene. Mutation analysis of SLC22A5 gene was carried out in eight Turkish patients from six families. Six patients presented with signs and symptoms of heart failure, cardiomyopathy, and low plasma carnitine levels, five of them with concurrent anemia. A patient with dilated cardiomyopathy had also facial dysmorphia, microcephaly, and developmental delay. Tandem MS analyses in siblings of the patients revealed two more cases with low plasma carnitine levels. SCD diagnosis was confirmed in these two cases by mutation screening. These two cases were asymptomatic but echocardiography revealed left ventricular dilatation in one of them. Carnitine treatment was started before the systemic signs and symptoms developed in these patients. Mean value of serum carnitine levels of the patients was 2.63±1.92μmol/L at the time of diagnosis. After 1year of treatment, carnitine values increased to 16.62±5.11 (p

This paper discusses the design considerations of a 10 GHz helix traveling wave tube using commercial electromagnetic simulation software CST-PIC/MWS. The dispersion characteristics of the TWT have been analyzed by modeling of a single turn electron-free slice in eigenmode solver. The return loss optimization of the input-output couplers is performed by using of transient solver. The complete model has been simulated and analyzed in particle-in-cell solver and the results are presented. © 2011 IEEE. 2011 30th URSI General Assembly and Scientific Symposium, URSIGASS 2011 -- 13 August 2011 through 20 August 2011 -- Istanbul -- 87252

Tyrosinemia type I (OMIM 276700) is a rare, autosomal recessive disorder caused by a deficiency in the fumarylacetoacetate hydrolase (FAH) enzyme. This study examined the spectrum of FAH gene mutation in 32 patients with tyrosinemia type I. In addition, clinical and biochemical findings were evaluated to establish a genotype-phenotype relationship in the patients. Mutation screening was performed using a 50K custom-designed resequencing microarray chip (TR_06_01r520489, Affymetrix) and sequencing analysis. Of the 12 different mutations found, 6 are categorized as novel. Three of the mutations-IVS6-1GA, D233V, and IVS3-3CG-are the most common in Turkish patients, comprising 25%, 17.1%, and 12.5% of mutant alleles, respectively.Clinical evaluations suggest that the spectrum of symptoms observed in the patients with very early and early disease were of the more nonspecific form, whereas the patients with late-presenting disease had more of the distinctive form over the course of the disease. This study adds support to the notion that the D233V mutation is specific to the Turkish population.

Since its discovery in early 1990s, hypoxia inducible factor 1 (HIF-1) has been increasingly recognized for its key role in transcriptional control of more than a hundred genes that regulate a wide-spectrum of cellular functional events, including angiogenesis, vasomotor control, glucose and energy metabolism, erythropoiesis, iron homeostasis, pH regulation, cell proliferation and viability. Evidence accumulated during the past 7 years suggests a critical role for HIF-1alpha in mediating cardioprotection. The purpose of our present article is to provide an updated overview on this important regulator of gene expression in the cellular stress-responsive and adaptive process. We have particularly emphasized the involvement of HIF-1 in the induction of cardioprotective molecules, such as inducible nitric oxide synthase (iNOS), hemeoxygenase 1 (HO-1), and erythropoietin (EPO), which in turn alleviate myocardial damages caused by harmful events such as ischemia-reperfusion injury. Despite these advances, further in-depth studies are needed to elucidate the possible coordination or interaction between HIF-1alpha and other key transcription factors in regulating protein expression that leads to cardioprotection.

Serine deficiency disorders are a new group of neurometabolic diseases resulting from a deficiency in one of the three enzymes in the biosynthetic pathway of L-serine. Deficiency of the enzyme 3-phosphoglycerate dehydrogenase (3-PGDH), which catalyzes the first step in the biosynthetic pathway, leads to congenital microcephaly, severe psychomotor retardation, and intractable seizures. We report a 4 1/2-year-old boy who presented with congenital microcephaly, psychomotor retardation, hypertonia, strabismus, and drug-resistant seizures due to 3-PGDH deficiency. His seizures responded to L-serine and glycine supplementation only. This potentially treatable disease should be borne in mind in patients with congenital microcephaly, psychomotor retardation and seizures. A timely diagnosis based on the detection of low cerebrospinal fluid levels of L-serine and glycine is expected to further increase the success of L-serine and glycine supplementation in these patients.

Bu çalışmanın amacı; Gençlik ve Spor Genel Müdürlüğü tarafından 8i ilde il spor merkezleribünyesinde uygulamaya konulan yaz spor okullanntn sporun topluma yaygınlaştırılınası sürecindekikatkılannı belirlemektir.Araştınnada tarama modeli yöntemi kuııanılmıştır. Araştırma problemine ilişkin mevcut bilgiler ilgililiteratürün taranmasıyla sistematik bir biçimde verilmiş ve konu hakkında teorik bir çerçeveoluşturulmuştur.Araştırmada veri toplama aracı olarak; Gençlik ve Spor Genel Müdürlüğü ve Türkiye İstatistikKurumu'ndan elde edilen istatistİki veri(er tablolara dönüştürülerek yorumlanmıştır.Araştınnada yaz spor okullan uygulamasına katılımın her yıl artarak devam ettiği, özellikle yüzme,futbol, basketbol ve voleybol branşlanndajeatıltmın çok fazla olduğu tespit edilmiştir.Sonuç olarak, yaz spor okulları uygulama

The peroxisomal biogenesis disorders (PBDs) comprise the Zellweger spectrum disorders (i.e., Zellweger syndrome, neonatal adrenoleukodystrophy, and infantile Refsum disease) and rhizomelic chondrodysplasia punctata. Peroxisomal biogenesis disorders can be caused by mutations in any of 13 currently known PEX genes, which encode peroxins involved in peroxisomal protein import and/or assembly of the organelle. We report here on a Turkish patient who presented with unusual clinical findings, that included non-immune hydrops, dermal erythropoiesis and hypoplastic toenails, as well as common dysmorphic features of Zellweger syndrome. The patient has also pulmonary hypoplasia, which has been reported in only a few patients with Zellweger syndrome. A peroxisomal biogenesis disorder was confirmed by enzyme analysis and abnormal very long-chain fatty acid (VLCFA) profiles in plasma and fibroblast and immunofluorescence microscopy studies. Subsequent molecular genetic analysis revealed a homozygous c.856C>T mutation (R268X) in the PEX3 gene, which made this patient the third to have a defect in this gene. In contrast to those of the two previously reported patients, the cells of this patient still contained peroxisomal membrane structures (ghosts), seen by immunofluorescence microscopy analysis. The case presented here and the two previously reported cases point out that a PEX3 gene defect may present with fairly heterogeneous clinical findings. This case also raises a possibility that hydrops fetalis may be associated with a PEX3 gene defect and that peroxisomal disorders can be considered in the etiology of hydrops fetalis as well as other cell organelle disorders when one is considering yet undiscovered complementation groups in peroxisomal disorders.

In maple syrup urine disease (MSUD), disease-causing mutations can affect the BCKDHA, BCKDHB or DBT genes encoding for the E1alpha, E1beta and E2 subunits of the multienzyme branched-chain alpha-keto acid dehydrogenase (BCKDH) complex. Here we summarize the MSUD genotypes of a cohort of 32 unrelated Turkish patients in whom both alleles at a single gene locus harbored presumable disease-causing nucleotide changes. The patients had different forms of MSUD, ranging from the severe classical form (26 patients) to severe and mild variants (6 patients). In all except two patients (92%), the mutations occurred homozygously. The mutational spectrum included 27 different sequence variations--12 changes in the BCKDHA, 10 in the BCKDHB, and 5 in the DBT genes. In 37% (12 patients) of a total of 64 alleles, the supposed disease-causing mutations were located in the BCKDHA gene, in 44% (14 patients) in the BCKDHB gene and in 19% (6 patients) in the DBT gene. The mutational profile is heterogeneous, although two mutations occurred three times and five mutations occurred twice. There was no cluster for a single mutation except for c.773GA (p.Cys258Tyr) in the BCKDHA gene, a hypothetical founder mutation in the Camlidere population.

The International Society for Optical Engineering (SPIE), Applications of Digital Image Processing XXXII -- 3 August 2009 through 5 August 2009 -- San Diego, CA -- 77872, This paper proposes the use of the Hilbert transform for analysis of fringe patterns, which are obtained in Michelson Interferometer. The fringe patterns are evaluated by Continuous wavelet transform and Hilbert transform algorithms to obtain phase map and refractive index. Continuous wavelet transform algorithm shows a better filtering effect. However Hilbert transform algorithm gives a noisy result, since its frequency spectrum has harmonic noise. Results show that the phase map is affected by Hilbert Filter. © 2009 SPIE.

Objective Juvenile idiopathic arthritis (JIA) is a childhood rheumatic disease of unknown etiology. Two subgroups of JIA, i.e., oligoarticular and polyarticular, are thought to have an autoimmune component, and show a higher female:male ratio. Skewed X chromosome inactivation (XCI) has previously been shown to be associated with scleroderma and autoimmune thyroiditis, 2 autoimmune disorders occurring predominantly in females. This study was undertaken to extend the analysis to the pediatric age group and to determine the XCI profiles of patients with JIA. Methods A polymorphic repeat in the androgen receptor gene was genotyped to determine XCI status in 81 female patients with JIA (21 with polyarticular disease and 60 with oligoarticular disease) and 211 healthy female controls. DNA obtained from venous blood samples was used for this analysis. Results Informative data were obtained on 62 JIA patients and 155 controls. Skewed XCI was observed in 14 patients (22.6%) and 11 controls (7.1%) (P = 0.0036), and extreme skewing was apparent in 8 patients (12.9%) and 2 controls (1.3%) (P = 0.0008). Conclusion Our findings in the present study indicate that skewed XCI may be a risk factor for the occurrence of autoimmune disorders, including JIA.

We present two siblings with identical clinical findings that seem to represent a previously unreported familial syndrome. Major findings involve three systems: pulmonary arterial hypertension, cardiac abnormalities including secundum-type atrial septal defect, and the hematopoietic system with intermittent neutropenia, lymphopenia, monocytosis, and anemia. The siblings also shared several minor abnormalities: pectus carinatum, long fingers, proximally placed thumb, broad nasal bridge, and high-arched palate. The male proband also had bilateral inguinal hernias and undescended testes. The same findings in two siblings suggest a genetic cause--either an autosomal recessive disorder or germline mosaicism in one parent for a dominant mutation. Investigations revealed a bone morphogenetic protein receptor 2 polymorphism in intron 4 in only one sibling, which was also present in unaffected maternal relatives.

Gelir düzeylerinin artması, sosyal yaşamda meydana gelen değişimler ve teknolojik gelişmelerle artan boş zamanlar dünya genelinde insanların tatil anlayışlarında değişmelere yol açarak alternatif turizm türlerinin ortaya çıkmasına sebep olmuştur. Spor ise alternatif bir turizm şekli olarak son yıllarda turizm sektörü içinde önemli bir yer almaya başlamıştır. Ülkemizde ve dünyada kayak sporları kış mevsiminin vazgeçilmez turistik aktiviteleri arasında yer alırken her geçen yıl, kış turizmine paralel olarak kayak merkezlerinde büyük gelişmelere neden olmuş ve kış sporları turizmine olan talebi arttırmıştır. Kış sporları turizmi potansiyeli açısından Türkiye sahip olduğu coğrafi ve iklim şartlarıyla önemli bir konuma sahiptir. Sarıkamış bölgesinin kış sporları değerlendirildiği bu çalışmada; bölgedeki mevcut durum ve planlanan yatırımlar ortaya konulup değerlendirilerek, yapılması gerekenler konusunda öneriler getirilmeye çalışılmıştır, The spare times with increase the incoming profit, changes the social experience and technological development, contributed alternative tourism species via chancing the holiday mean. Recently, sports take part in the sector as a tourism type. Skiing sports are beginning indispensable touristic activity in our country and the world, and it caused the development of the skiing centre. The Turkey have an important position with its climatic condition in the terms of winter sports. In this study that include assessment of the Sarıkamıs about potential of the winter sports; situation of this area considered with planned enterprise and suggested required things

Meme büyütme veya rekonstrüksiyonlarında alloplastik implant materyalleri yaygın olarak kullanılmaktadır. Fibroz kapsüler kontraksiyon, meme büyütme sonrasında sık görülen bir komplikasyon olup kontraksiyon riski zamana bağlı olarak artmaktadır. Kontrakte fibroz kapsüldeki kalsifikasyonlar meme gland dokusu ve büyük pektoral kasta basınca bağlı olan atrofilere neden olabilmektedir. Bu uzun dönem komplikasyon Krakatau sendromu olarak adlandırılır. Bu yazıda tipik Krakatau sendromu olan 45 yaşında kadın hasta sunuldu. 22 yıl önce meme büyütme ameliyatı geçiren hastanın muayenesinde, ileri derecede kapsüler kontraktür bulgularına ilave olarak palpasyonla sertleşmiş meme dokuları ve belirgin deformasyon görünümü eşlik ediyordu. Hastanın implantı çıkarıldığında, kapsülde kalsifikasyonlar, gland dokuları ve pektoral kaslarda atrofi gözlendi., Alloplastic materials for breast augmentation and reconstruction have been commonly used. Fibrous capsuler contraction is a frequent complication of breast augmentation and the risk of contracture steadily increases with time. Calcifications of the contracted fibrous capsule can cause pressure atrophy of the gland and pectoralis major muscle. This long-term complication is named Krakatau syndrome. In our report, we present a representative case of Krakatau syndrome in a 45 years old woman. She had undergone breast augmentation 22 years previously. On examination a severe capsuler contraction was seen with hard breasts and a visible deformity. After removal of the implants, calcified capsule, atrophy of the mammary glands and pectoralis mıuscle was observed.

Dev fibroadenomlar puberte döneminde memede tek taraflı hızlı büyüme ile karşımıza çıkan iyi huylu kitlelerdir. Tanı meme biyopsisi ile konur. Tedavisi konservatih cerrahi girişimlerdir. Bu yazıda, memede dev fibroadenom nedeni ile kliniğimizde tedavi edilen bir olgu sunuldu. Olgu nadir görülmesi nedeni ile literatür bilgileri ışığında tartışıldı., Giant fibroadenomas are benign, discrete lesions that present during puberty as unilateral, rapidly growing breast masses. Diagnosis is made by breast biopsy. Treatment involves surgical excision. We present a case of giant breast tumor treated in our department. This rare case is presented with a review of the recent literature.

42nd Annual Symposium of the SSIEM -- SEP, 2005 -- Anaheim, FRANCE Dursun, Ali/0000-0003-1104-9902 WOS: 000249018900018 PubMed: 17206456 Here we report a newborn with VLCAD deficiency with a severe neonatal onset type who presented with hypoglycemia, cardiomyopathy, mild hepatomegaly and slight hypoalbuminemia. The patient was also homozygous for a new missense mutation (R456H). Postmortem examination of the liver, heart and skeletal muscle revealed diffuse lipid accumulation in various amounts. Mild lobular and portal fibrosis as well as severe macrovesicular steatosis were also found in the liver. The fatal course of the patient may have resulted from diffuse lipid accumulation in the liver and myocardium, which probably began during the intrauterine life with slight hypoalbuminemia as a silent marker of this process. SSIEM

Bu çalışmanın amacı; Türkiye Cumhuriyeti anayasalarında, kanunlarında ve kalkınma planlarında sporla ilgili öngörülen hedeflerin gerçekleşme düzeylerini tespit etmektir. Araştırmanın evrenini Gençlik ve Spor Genel Müdürlüğünde çalışan personel, örneklemini ise Merkez Teşkilatında çalışan, Genel Müdür Yardımcıları, Daire Başkanları, Federasyon Başkanları, Federasyon Genel Sekreterleri, Şube Müdürleri, Şef ve Uzmanlardan oluşan 308 yönetici personel oluşturmaktadır. Çalışmada Türk Spor Politikalarında öngörülen hedeflerin gerçekleşme düzeylerini tespit etmeye yönelik bir anket uygulanmıştır. Anket hazırlanırken uzman kişilerin görüşleri alınmış, 30 kişilik bir Ön guruba pilot uygulama yapılarak son şekli verilmiştir. Birinci bölümde kişisel bilgilere, ikinci bölümde ise Türk Spor Politikalarının temelini oluşturan Anayasa, Kanunlar, Kalkınma Planları ve Hükümet Programlarında sporla ilgili öngörülen hedeflerin gerçekleşme düzeylerini tespit etmeye yönelik sorulara yer verilmiştir. Anketlerden elde edilen veriler SPSS programında frekans ve yüzde analizleri yapılarak tablolaştırılmış ve değerlendirilmiştir. Araştırma sonucunda, Türk Spor Politikalarında öngörülen hedeflerin istenilen düzeyde gerçekleşmediği tespit edilmiştir. Yöneticilerin büyük bir çoğunluğu, sporun topluma yeterli bir şekilde yaygınlaştırılamadığını belirtirken, ayrıca tesislerin nitelik ve nicelik bakımından yetersiz olduğu ve var olan tesislerin halkın kullanımına yeterli bir şekilde sunulamadığı, özel sektörün katkısının artırılamadığı ve olimpiyatlarla ilgili çalışmaların yetersiz olduğu yönünde görüş bildirdikleri tespit edilmiştir., The aim of this study is to determine the levels of the realizations of the preaimed objectives relating sports, mentioned in the Turkish Republics Constitution, laws, development laws and government policies and programmes. The circle of the research covers the employees working for Directorate General Of Youth and Sports. The sampling on the other hand is done within 308 administrative employees at the Central Organization, working as; Deputy General Directors , Section Presidents, Presidents of the Federations, General Secretaries of the Federations , Branch Directors, Chiefs and Experts. In the study a poll is carried out to determine the levels of realization of the preaimed objectives within the Turkish Policies of sports. During the preparation of the poll; thoughts of experts have been asked and finalised by a pilot application carried on a pregroup of 30 persons. The first section is saved for personal information and in the second section questions asked regarding the levels of realization of the preaimed objectives within the constituon, laws, development laws and government policies and programmes regarding sports which are the basis of the Turkish Sports Policies.The results of the polls have been tableised and evaluated using SPSS program. As a results of the research , it is determined that the Turkish Sports Policies have not been achieved. Majority of the pollers stated that sports could not be commonised within the society and on the other hand the sports complexes are inadequate regarding to quality and quantity. And the present sports complexes could not be presented to public use efficiently. And the input of private sector could not be increased and efforts regarding olympiads is inadequate.

Kondroid siringoma ter bezi glandlarından köken alan, genellikle altıncı veya yedinci dekatta ortaya çıkan, nadir görülen bir tümördür. Bu nadir görülen tümörün spesifik bir makroskobik görünümü olmadığından, sık görülen diğer tümöral lezyonlarla karıştırılabilir. Çalışmamızda üst dudağında kondroid siringoma olan otuzyedi yaşında erkek bir olgu sunularak bu nadir tümörün tanı ve tedavisi hakkında literatürdeki bilgiler gözden geçirilmiştir., Chondroid syringoma is a rare tumor which is derived from the sweat glands. It is usually encountered in the sixth or seventh decade of life. Since it is rare and has no spesific macroscopic appearance, it may be confused with the other frequent skin lesions. In this article, a case of a 37 year-old male patient who had a chondroid syringoma on his upper lip was presented and the literature about the diagnosis and the tretment of this rare tumor is rewieved.

Objective Biotinidase deficiency is an autosomal recessively inherited disorder characterized by neurological and cutaneous features, including sensorineural hearing loss. Although many features of the disorder are reversible following treatment with biotin, the hearing loss appears to be irreversible. In the present study, hearing status of patients with biotinidase deficiency is characterized in a Turkish population. Methods Subjective and objective audiologic tests were performed on 20 children with profound biotinidase deficiency. Results Sensorineural hearing loss occurs in approximately 55% of the children with biotinidase deficiency. The hearing loss varies in severity from mild to profound hearing loss. In children diagnosed immediately after birth because they had an older sibling with the disorder, statistically significant differences were found between ABR results and age of diagnosis (p

Glutaryl-CoA dehydrogenase (GCDH) deficiency is a rare inborn disorder of L-lysine, L-hydroxylysine, and L-tryptophan metabolism complicated by striatal damage during acute encephalopathic crises. Three decades after its description, the natural history and how to treat this disorder are still incompletely understood. To study which variables influenced the outcome, we conducted an international cross-sectional study in 35 metabolic centers. Our main outcome measures were onset and neurologic sequelae of acute encephalopathic crises. A total of 279 patients (160 male, 119 female) were included who were diagnosed clinically after clinical presentation (n = 218) or presymptomatically by neonatal screening (n = 23), high-risk screening (n = 24), or macrocephaly (n = 14). Most symptomatic patients (n = 185) had encephalopathic crises, characteristically resulting in bilateral striatal damage and dystonia, secondary complications, and reduced life expectancy. First crises usually occurred during infancy (95% by age 2 y); the oldest age at which a repeat crisis was reported was 70 mo. In a few patients, neurologic disease developed without a reported crisis. Differences in the diagnostic criteria and therapeutic protocols for patients with GCDH deficiency resulted in a huge variability in the outcome worldwide. Recursive partitioning demonstrated that timely diagnosis in neurologically asymptomatic patients followed by treatment with L-carnitine and a lysine-restricted diet was the best predictor of good outcome, whereas treatment efficacy was low in patients diagnosed after the onset of neurologic disease. Notably, the biochemical phenotype did not predict the clinical phenotype. Our study proves GCDH deficiency to be a treatable disorder and a good candidate for neonatal screening.

151- OZET Bu araştırmanın amacı, spor kulüpleri için alternatif bir finans yöntemi olan halka açılmanın spor kulüplerinin finansal yapılan üzerine etkilerini incelemek ve uygulanan modeller açısından bazı öneriler getirmektir. Bu amaçla; ilgili literatür incelenmiş ve mevcut duruma ilişkin bilgilere yer verilmeye çalışılmıştır. Araştırma kapsamında şirketlerin genel müdürleri ile mülakatlar yapılmış ayrıca şirketlerin mali tabloları finansal analize tabi tutularak araştırmanın problemine çözüm aranmıştır. Araştırmanın evrenini Türkiye'de halka açılmış olan profesyonel futbol kulübü şirketleri olan Galatasaray Sportif ve Sınai ve Ticari yatırımlar A.Ş., Beşiktaş Futbol Yatırımları A.Ş., Fenerbahçe Sportif Hizmetler Sanayi ve Ticaret A.Ş. ve Trabzonspor Sportif Yatırım ve Ticaret A.Ş. oluşturmuştur. Ancak Trabzonspor Sportif Yatırım ve Ticaret A.Ş. araştırmanın yapıldığı tarihte (Nisan 2005) halka açıldığından halka açıldıktan sonraki mali tabloları açıklanmadığı için analiz kapsamı dışında tutulmuştur. Araştırmada; şirketlerin mali tabloları karşılaştırmalı tablolar analizi, yüzde yöntemi ile analiz, eğilim yüzdeleri yöntemi ile analiz ve oran analizi gibi temel analiz teknikleri ile analiz edilmiştir. Sonuç olarak; Analize tabi tutulan kulüp şirketlerinin halka açılma öncesi mali yapılan ile halka açılma sonrası mali yapılan karşılaştırdığında, halka açılma ile sağlanan gelirlerinde etkisiyle üç şirketinde mali yapısında iyileşme olduğu tespit edilmiştir. Buna göre Türkiye'de spor kulüplerinin şirketleşip halka açılmalar gerektiği söylenebilir. -152- SUMMARY The purpose of this study is to examine the effects on the financial structure of sport club's initial public offering as an alternative finance method and giving some suggestions to applied models. For this aim the related literature had researched and tried to give related information about current situation. In scope of research some interviews had been made with general directors of companies and the fiscal tables had been experienced to financial analysis for finding solution to the problem of study. The population of the study was the sports clubs company that were initial public offering like Galatasaray Sportive Joint-Stock Company, Beşiktaş Sportive Joint-Stock Company, Fenerbahçe Sportive Joint-Stock Company and Trabzonspor Sportive Joint-Stock Company. But in April 2005, the same dates of searching, Trabzonspor Sportive Joint-Stock Company had initial public offering, however the fiscal tables can't declare so Trabzonspor Sportive Joint-Stock Company is outside of the analysis. In this study the financial tables of companies had analyzed by the basic analysis techniques like comparative tables analysis, analysis by percentage method, tendency percentage method and ratio analysis. As a result; the comparison of analyzed club companies' previous and latter financial state of the initial public offering, the three companies financial state gets better by the incomes of initial public offering. According to this it could be said the sport clubs have to be companies and have to initial public offering. 202

Familial hypercholesterolaemia (FH) is an autosomal dominant disorder of lipoprotein metabolism. In the majority of patients FH is caused by mutations in the gene for the low-density lipoprotein receptor (LDLR), and to date more than 700 mutations have been reported worldwide. In this study, 36 paediatric patients with a clinical diagnosis of FH (20 homozygous and 16 heterozygotes) were screened for mutations in the LDLR gene. Each exon, with intron-exon junctions, was screened by capillary fluorescent SSCP (F-SSCP) and heteroduplex analysis. Samples showing different band patterns were sequenced. Ten novel (including three frame shift small deletions or insertions) and seven known mutations were detected. A total of 37 out of the predicted 56 FH-causing alleles were identified (66.1%). No patients with the R3500Q mutation in the APOB gene were found. W556R was the most common mutation, explaining 21.4% of the predicted defective LDLR alleles. The novel sequence changes were deemed to be pathogenic if they altered a conserved amino acid (L143P, D147E, Q233H-C234G, C347G) or occurred in or close to a splice site (IVS 16+5) and were absent in DNA from 50 healthy Turkish subjects. These data confirm the genetic heterogeneity of FH in Turkey, and demonstrate the usefulness of F-SSCP for mutation detection.

Classical citrullinemia (CTLN1), a rare autosomal recessive disorder, is caused by mutations of the argininosuccinate synthetase (ASS) gene, localized on chromosome 9q34.1. ASS functions as a rate-limiting enzyme in the urea cycle. Previously, we identified 32 mutations in the ASS gene of CTLN1 patients mainly in Japan and the United States, and to date 34 different mutations have been described in 50 families worldwide. In the present study, we report ASS mutations detected in 35 additional CTLN1 families from 11 countries. By analyzing the entire coding sequence and the intron-exon boundaries of the ASS gene using RT-PCR and/or genomic DNA-PCR, we have identified 16 novel mutations (two different 1-bp deletions, a 67-bp insertion, and 13 missense) and have detected 12 known mutations. Altogether, 50 different mutations (seven deletion, three splice site, one duplication, two nonsense, and 37 missense) in 85 CTLN1 families were identified. On the basis of primary sequence comparisons with the crystal structure of E. coli ASS protein, it may be concluded that any of the 37 missense mutations found at 30 different positions led to structural and functional impairments of the human ASS protein. It has been found that three mutations are particularly frequent: IVS6-2A>G in 23 families (Japan: 20 and Korea: three), G390R in 18 families (Turkey: six, U.S.: five, Spain: three, Israel: one, Austria: one, Canada: one, and Bolivia: one), and R304W in 10 families (Japan: nine and Turkey: one). Most mutations of the ASS gene are "private" and are distributed throughout the gene, except for exons 5 and 12-14. It seems that the clinical course of the patients with truncated mutations or the G390R mutation is early-onset/severe. The phenotype of the patients with certain missense mutations (G362V or W179R) is more late-onset/mild. Eight patients with R86H, A118T, R265H, or K310R mutations were adult/late-onset and four of them showed severe symptoms during pregnancy or postpartum. However, it is still difficult to prove the genotype-phenotype correlation, because many patients were compound heterozygotes (with two different mutations), lived in different environments at the time of diagnosis, and/or had several treatment regimes or various knowledge of the disease.

Transient nonketotic hyperglycinemia is characterized by clinical and biochemical findings similar to those seen in classic nonketotic hyperglycinemia. Abnormalities in amino acids are partially or completely resolved in a period ranging from days to months. Almost all patients with the classic form of nonketotic hyperglycinemia survive with severe neurologic sequela, whereas most of the patients with the transient form exhibit normal development. Therefore, distinguishing the transient form of nonketotic hyperglycinemia from classic nonketotic hyperglycinemia is important to predict outcome of the patients. Transient nonketotic hyperglycinemia has been reported in only seven neonates. This article adds two cases to the transient nonketotic hyperglycinemia and reviews the relevant literature. Common clinical features were determined, and presence of miotic pupils was stressed.

Background and aim Lead, mercury and cadmium are widely exposed environmental pollutants throughout the world. In this study, we aimed to investigate the level of exposure to lead(Pb), mercury(Hg) and cadmium(Cd) during intrauterine life. Methods We included 123 mother-infant pairs between December 2006 and January 2007. Umbilical cord blood collected immediately after delivery while breast milk and newborn hair samples collected between 3–10th postpartum days. All the specimens analyzed by Inductively Coupled Plasma Mass Spectrometry. Results Cord blood samples Pb was present in 99.2%(the mean 1.66±1.6µg/dl) while Hg in only 1.7% and Cd in 19.8%(ranged 0–6.71µg/L). Cord blood Pb was higher than ≥2µg/dl in 29% of the samples. Pb, Hg and Cd were detectable in all the newborn hair samples. Among breast milk samples 83.2% had detectable lead levels(mean 14.5±12.1µg/L). Presence of Hg and Cd in breast milk samples were 53.3% and 9% respectively. Cord blood lead levels were significantly higher when maternal age >35 years. Breast milk Cd levels were significantly higher in women who were residing close to the major city waste site. Cord blood Cd levels were significantly higher in women consuming more than two fish weekly. Maternal exposure to environmental tobacco smoking(ETS) resulted increased newborn hair Pb and Cd levels. Conclusion Intrauterine heavy metal exposure is an important concern for pediatricians. Most samples had detectable levels for Pb, Hg, Cd indicating long term maternal exposure and considerable number exceeds the present accepted safety levels at cord and breast milk samples. Preventing ETS, limiting fish consumption and improved living conditions for pregnant women may decrease exposure levels.

Maple syrup urine disease (MSUD), the most frequently occurring organic acidaemia in Turkey, is caused by a deficiency of the activity of branched-chain keto acid dehydrogenase enzyme (BCKAD) complex. Mutation analysis of the E1alpha, E1beta, and E2 genes of the BCKAD complex in 12 Turkish MSUD patients yielded three disease-specific mutations and a polymorphism in the E1alpha gene, none in the E1beta gene and one mutation in the E2 gene. Among them, three missense mutations (Q80E, C213Y, T106M) and the F280F polymorphism occurring in the E1alpha gene and the splice site mutation (IVS3 - 1G > A) in the E2 gene were novel. Three of the missense mutations and the splicing mutation occurred homozygously and caused classical MSUD. One patient carried the splicing mutation homozygously and the T106M mutation in the heterozygous state; this patient is the first case having simultaneously two different mutations in two different genes in the BCKAD complex. IVS3 - 1G > A splicing mutation detected on the E2 gene causes deletion of the first 14 bp of exon 3 in the mutant mRNA extending between 190 and 204 nt. The deletion spans the cleavage point between mitochondrial targeting and lipoyl-bearing site of the E2 protein.

Thirteen Turkish patients with hereditary fructose intolerance (HFI) were screened for the three common mutations, A149P, A174D and N334K, in the aldolase B gene that have been detected frequently in European population. We found that nine of the patients carry the A149P mutation in both alleles, which corresponds to a frequency of about 55%. Single-strand conformation analysis of all coding exons of the gene was also performed to detect unknown mutations in four patients not carrying the three common mutations. No aberrant migration patterns were observed in these patients.

Neuroleptic malignant syndrome (NMS) is a severe and potentially lethal complication of neuroleptic drug use. Haloperidol, chlorpromazine, £uphenazine, use of the neuroleptics with other medications including anticholinergics, lithium and benzodiazepines, and withdrawal from dopamine agonists are commonly implicated factors in NMS. The triad of fever, tachycardia, and rigidity characterizes the presentation in children and adults. Other clinical symptoms include increased heart rate, alteration in consciousness, blood pressure £uctation, dystonia, diaphoresis and tremor. Raised CPK, WBC, liver transaminases and serum sodium are the most frequently detected laboratory ¢ndings. NMSmay develop immediately after the drugs taken or may be delayed up to one or two weeks after the initiation of the treatment, being independent of the dose of the drugs. It has been reported that dysregulated sympathetic nervous system hyperactivity is responsible for most of the features of NMS. Treatments for patients with NMS include dantrolene, bromocriptine, benzodiazepines, barbiturates, propranolol, anticholinergic drugs, amantadine and L-dopa, and electroconvulsive therapy (Addonizio et al 1987; Gurrera 1999; Levenson 1985; Silva et al 1999). We report here NMS in a patient with citrullinaemia. To our knowledge this is the ¢rst reported NMS case associated with an inborn error of metabolic disease and we emphasize that patients with inborn errors of metabolic disease might be at risk for the development of NMS. Patient T.K., an 8-year-old girl, was the only living child of consanguineous parents. The diagnosis of citrullinaemia had beenmade at 8months at ¢rst admission. Themother had had 13 pregnancies, six of which had been spontaneous abortions and six had been live births who subsequently had died between 3 days and 3.5 years. Two siblings had been diagnosed as having citrullinaemia previously. The patient was being followed up on a low-protein diet including special formula (Milupa UCD), arginine (100 mg/kg per day) and sodium benzoate (250 mg/kg per day). She was admitted to our hospital with complaints of agitation and tendency to sleep. On physical examination, she was confused and agitated, and her cerebellar ¢ndings were abnormal. The laboratory investigations revealed that serum ammonia was 141 mg/dl (normal values 60^120 mg/dl), WBC 15 700/mm3, creatinine phophokinase (CPK) 124 IU/L (normal values 0^190 mg/dl). Renal and liver funcJ. Inherit. Metab. Dis. 23 (2000) 841^842 # SSIEM and Kluwer Academic Publishers. Printed in the Netherlands.

Dihydropteridine reductase (DHPR) catalyses the conversion of quinonoid dihydrobiopterin (qBH2) to tetrahydrobiopterin (BH4), which serves as the obligatory cofactor for the aromatic amino acid hydroxylases. DHPR deficiency, caused by mutations in the QDPR gene, results in hyperphenylalaninemia and deficiency of various neurotransmitters in the central nervous system, with severe neurological symptoms as a consequence. We have studied, at the clinical and molecular levels, 17 patients belonging to 16 Turkish families with DHPR deficiency. The patients were detected at neonatal screening for hyperphenylalaninemia or upon the development of neurological symptoms. To identify the disease causing molecular defects, we developed a sensitive screening method that rapidly scans the entire open reading frame and all splice sites of the QDPR gene. This method combines PCR amplification and "GC-clamping" of each of the seven exonic regions of QDPR, resolution of mutations by denaturing gradient gel electrophoresis (DGGE), and identification of mutations by direct sequence analysis. A total of ten different mutations were identified, of which three are known (G23D, Y150C, R221X) and the remaining are novel (G17R, G18D, W35fs, Q66R, W90X, S97fs and G149R). Six of these mutations are missense variants, two are nonsense mutations, and two are frameshift mutations. All patients had homoallelic genotypes, which allowed the establishment of genotype-phenotype associations. Our findings suggest that DGGE is a fast and efficient method for detection of mutations in the QDPR gene, which may be useful for confirmatory DNA-based diagnosis, genetic counselling and prenatal diagnosis in DHPR deficiency.

Bu çalışmanın amacı; Türkiye Cumhuriyeti anayasalarında, kanunlarında, kalkınma planlarında ve hükümet programlarında sporla ilgili öngörülen hedeflerin gerçekleşme düzeylerinin tespit edilmesini oluşturmaktadır. Araştırmanın evrenini Gençlik ve Spor Genel Müdürlüğünde çalışan personel, örneklemini ise Merkez Teşkilâtında çalışan, Genel Müdür Yardımcıları, Dâire Başkanları, Federasyon Başkanları, Federasyon Genel Sekreterleri, Şube Müdürleri, Şef ve Uzmanlardan oluşan 308 yönetici personel oluşturmaktadır. Çalışmada Türk Spor Politikalarında öngörülen hedeflerin gerçekleşme düzeylerini tespit etmeye yönelik bir anket uygulanmıştır. Anket hazırlanırken uzman kişilerin görüşleri alınmış, 30 kişilik bir ön guruba pilot uygulama yapılarak son şekli verilmiştir. Birinci bölümde kişisel bilgilere, ikinci bölümde ise Türk Spor Politikalarının temelini oluşturan Anayasa, Kânunlar, Kalkınma Planlan ve Hükümet Programlarında sporla ilgili öngörülen hedeflerin gerçekleşme düzeylerini tespit etmeye yönelik sorulara yer verilmiştir. Anketlerden elde edilen veriler SPSS programında frekans ve yüzde analizleri yapılarak tablolaştırılmış ve değerlendirilmiştir. Araştırma sonucunda, Türk Spor Politikalarında öngörülen hedeflerin istenilen düzeyde gerçekleşmediği tespit edilmiştir. Deneklerin büyük bir çoğunluğu, sporun topluma yeterli bir şekilde yaygınlaştırılamadığını belirtirken, ayrıca tesislerin nitelik ve nicelik bakımından yetersiz olduğu ve var olan tesislerin halkın kullanımına yeterli bir şekilde sunulamadığı, özel sektörün katkısının artırılamadığı, nitelik ve nicelik olarak eğitimde (spor idareciliği,antrenörtük, hakemlik.vb.) yeterli düzeye ulaşılamadığı ve olimpiyatlarla ilgili çalışmaların yetersiz olduğu yönünde görüş bildirdikleri tespit edilmiştir. The aim of this study is to determine the levels of the realizations of the preaimed objectives relating sports, mentioned in the Turkish Republics Constitution, laws, development laws and government policies and programmes. The circle of the research covers the employees working for Directorate General Of Youth and Sports. The sampling on the other hand is done within 308 administrative employees at the Central Organization, working as; Deputy General Directors, Section Presidents, Presidents of the Federations, General Secretaries of the Federations, Branch Directors, Chiefs and Experts. In the study a poll is carried out to determine the levels of realization of the preaimed objectives within the Turkish Policies of sports. During the preparation of the poll; thoughts of experts have been asked and finalised by a pilot application carried on a pregroup of 30 persons. The first section is saved for personal information and in the second section questions asked regarding the levels of realization of the preaimed objectives within the constituon, laws, development laws and government policies and programmes regarding sports which are the basis of the Turkish Sports Policies. The results of the polls have been tableised and evaluated using SPSS program.-63- As a results of the research, it is determined that the Turkish Sports Policies have not been achieved. Majority of the pollers stated that sports could not be commonised within the society and on the other hand the sports complexes are inadequate regarding to quality and quantity. And the present sports complexes could not be presented to public use efficiently. And the input of private sector could not be increased and in education (sports administration.coaching.reffereing etc.) satisfactory the quality and quantity and efforts regarding olympiads is inadequate. 83