Namik Ozbek

Interleukin-12 Receptor β1 Chain Deficiency in a Child with Disseminated Tuberculosis

An 11-year-old girl who presented with disseminated tuberculosis associated with secondary hemophagocytosis received a diagnosis of interleukin-12 receptor beta 1 chain deficiency. This diagnosis of immunodeficiency should, therefore, be considered for children with disseminated tuberculosis, even in the absence of any personal or familial history of prior infection by weakly pathogenic Salmonella and Mycobacterium species.

Genotype-phenotype correlation in combined deficiency of factor V and factor VIII

Combined deficiency of factor V and factor VIII (F5F8D) is caused by mutations in one of 2 genes, either LMAN1 or MCFD2. Here we report the identification of mutations for 11 additional F5F8D families, including 4 novel mutations, 2 in MCFD2 and 2 in LMAN1. We show that a novel MCFD2 missense mutation identified here (D81Y) and 2 previously reported mutations (D89A and D122V) abolish MCFD2 binding to LMAN1. Measurement of platelet factor V (FV) levels in 7 F5F8D patients (4 with LMAN1 and 3 with MCFD2 mutations) demonstrated similar reductions to those observed for plasma FV. Combining the current data together with all previous published reports, we performed a genotype-phenotype analysis comparing patients with MCFD2 mutations with those with LMAN1 mutations. A previously unappreciated difference is observed between these 2 classes of patients in the distribution of plasma levels for FV and factor VIII (FVIII). Although there is considerable overlap, the mean levels of plasma FV and FVIII in patients with MCFD2 mutations are significantly lower than the corresponding levels in patients with LMAN1 mutations. No differences in distribution of factor levels are observed by sex. These data suggest that MCFD2 may play a primary role in the export of FV and FVIII from the ER, with the impact of LMAN1 mediated indirectly through its interaction with MCFD2.

SERUM PRO-HEPCIDIN LEVELS AND RELATIONSHIPS WITH IRON PARAMETERS IN HEALTHY PRETERM AND TERM NEWBORNS

A recently isolated peptide hormone, hepcidin, is thought to be the principal regulator of iron homeostasis. Hepcidin acts by limiting intestinal iron absorption and promoting iron retention in reticuloendothelial cells. Its precursor peptide form is called pro-hepcidin. The aims of this study were to determine serum pro-hepcidin levels in healthy preterm and term newborns, and to assess possible relationships between pro-hepcidin and serum iron, serum ferritin, and transferrin. A serum sample was collected from each of 26 healthy preterm (gestational age < 37 weeks) and 16 healthy, full-term, appropriate-for-gestational age babies. The preterm babies were also divided into 2 subgroups based on gestational age. Samples were analyzed for complete blood count, serum iron and ferritin concentrations, iron-binding capacity, and transferrin and pro-hepcidin levels. Group findings were compared and correlations between pro-hepcidin and the iron parameters were tested. The respective serum pro-hepcidin levels (mean ± SD) in the 16 healthy term and 26 healthy preterm newborns were 482 ± 371.9 ng/mL and 496.7 ± 443.5 ng/mL. Analysis revealed no significant correlations between serum pro-hepcidin level and serum iron, serum ferritin, or transferrin in the preterm or term newborns. Pro-hepcidin levels were not correlated with gestational age in the preterm group. The results indicate that healthy preterm and term newborns have high pro-hepcidin levels.

Successful Use of Recombinant Factor VIIa (NovoSeven) During Cardiac Surgery in a Pediatric Patient with Glanzmann Thrombasthenia

Glanzmann thrombasthenia is a rare, hereditary, congenital disorder of platelet function characterized by inappropriate bleeding that is difficult to control. Recombinant activated factor VII (rFVIIa) is a new treatment that is used to stop bleeding and provide surgical support for these patients. This report describes the use of rFVIIa to prevent serious bleeding during and after open-heart surgery in a child with Glanzmann thrombasthenia.

Maternal–Fetal Proinflammatory Cytokine Gene Polymorphism and Preterm Birth

Association between maternal-fetal proinflammatory cytokine genotype and preterm birth was studied. Isolated genomic DNA from maternal and cord blood samples of 100 preterm and 101 term labors were used for TNFα (-238G/A, -308G/A), IL-1α (4845G/T), and IL-1β (-511C/T) genotyping. TNFα -238 GA genotype in term neonates was significantly higher than the premature neonates (p<0.05). Maternal-fetal TNFα -238 heterozygosity was associated with term labor (p<0.05). TNFα -308 GA and AA genotypes were associated with term labor (mothers and neonates, respectively; p<0.05 and p<0.001). The incidence of term labor was significantly increased in TNFα -308 GA genotype. If a -308GA carrier has a fetus with GG genotype, the incidence of preterm labor increases (p<0.01). The 4845 T allele was significantly higher in preterm mothers and neonates (p<0.001 and p<0.001). The effect of maternal-fetal genotype for the pregnancy outcome reveals that maternal 4845GG and GT genotypes increase term labor incidence, whereas fetal 4845 TT genotype was a significant independent risk factor for preterm birth (p<0.01). IL-1β -511 TT genotype was significantly higher in preterm neonates. The preterm labor risk was significantly increased in maternal -511 TT genotype and fetal CT genotypes, whereas with maternal -511 CT or TT genotypes or a -511 TT fetus, the incidence of term pregnancy increases (p<0.01).

PAI-1 gene 4G/5G polymorphism, cytokine levels and their relations with metabolic parameters in obese children

Obesity is associated with the changes of plasminogen activator inhibitor-1 (PAI-1), tumor necrosis factor-alpha (TNFalpha) and transforming growth factor beta (TGFbeta) levels. However, the precise effect of the 4G allele on obesity is still contradictory. Here, we aimed to elucidate the role of the 4G/5G polymorphism of the PAI-1 gene on the PAI-1 level and determine the associations between cytokines, glucose and lipid metabolism parameters in obese children. Thirty-nine obese children (mean age 11.4 +/- 3.3 years) and 38 age-matched healthy control group (mean age 10.3 +/- 3.5 years) were included in the study. In all cases, serum levels of glucose, lipid and insulin were measured, homeostasis model assessment of insulin resistance (HOMA-IR) was calculated, and 4G/5G polymorphism of PAI-1 gene, plasma PAI-1 level and serum TNFalpha and TGFbeta levels were studied. The mean relative body mass index (BMI) and HOMA-IR score, VLDL, TG, insulin, PAI-1, TNFalpha levels were higher, and HDL and TGFbeta levels were lower in the obese group. The frequency of the 4G/4G genotype was considerably higher in obese children than in controls. Also, a positive correlation was found between PAI-1 and TNFalpha levels, and relative BMI, HOMA-IR score, insulin, TG, HDL levels. TGFbeta was inversely correlated only with relative BMI. There was no correlation among three cytokines. In conclusion, childhood obesity contributes to higher PAI-1 and TNFalpha and lower TGFbeta levels. Especially PAI-1 and TNFalpha accompany insulin resistance and dyslipidemia.

Prevalence of Thrombophilic Mutations and ACE I/D Polymorphism in Turkish Ischemic Stroke Patients

The aim of this study was to evaluate the prevalence of factor V Leiden (FVL), prothrombin G20210A, methylenetetrahydrofolate reductase (MTHFR) C677T gene mutations, and angiotensin-converting enzyme (ACE) I/D polymorphism in ischemic stroke (IS) patients. A total of 162 Turkish IS patients were included and analyzed according to stroke subtype by the TOAST classification. Their genotype data were compared with those of the control group, representing the healthy population, using the χ2 test. The frequency of FVL heterozygocity was 12.3% in this series—higher than that in the normal population (9.8%; statistically insignificant, P = .478). The frequency of the ACE D/D genotype in all stroke patients and those with stroke of undetermined etiology was higher than that in our population (52.5% and 59.2%, respectively, vs 39.3%; statistically significant, P = .034, P = .020). Our results may suggest that ACE D/D genotype is a risk factor for IS, particularly in those with stroke of undetermined etiology in the Turkish population.

Effect of iron deficiency anemia on renal tubular function in childhood

Abstract.Little is known about renal function in children with iron deficiency anemia. The purpose of this study was to investigate renal tubular function in these children. We compared renal tubular function in 20 children with iron deficiency anemia with 20 healthy age-matched controls. Blood and urine samples were obtained for hematological and biochemical analysis. Mean fractional excretion of sodium and mean urinary N-acetyl-β-D-glucosaminidase/creatinine were significantly higher in the children with iron deficiency anemia than in controls (P<0.05). Hemoglobin levels were negatively correlated with urinary N-acetyl-β-D-glucosaminidase/creatinine (r= -0.44, P=0.015), but were not correlated with fractional excretion of sodium (r= -0.29, P=0.13). There was no correlation between urinary N-acetyl-β-D-glucosaminidase/creatinine and fractional excretion of sodium (r=0.32, P=0.09). The results suggest that children with iron deficiency anemia have impaired renal tubular function.

Subcutaneous fat necrosis of the newborn associated with anemia.

Abstract: Subcutaneous fat necrosis (SFN) of the newborn characteristically affects full‐term infants who have experienced perinatal distress, such as hypothermia, obstetric trauma, or asphyxia. We report a newborn who had pallor, deep breathing, and severe anemia immediately after birth. She developed SFN on the fourth postnatal day. Her condition improved after blood transfusions and the skin lesions resolved in 6 weeks. This appears to be the first report of SFN associated with anemia.

Analysis of prothrombotic mutations and polymorphisms in children who developed thrombosis in the perioperative period of congenital cardiac surgery.

In this study, we investigated some of the prothrombothic mutations and polymorphisms in 15 children with congenital cardiac malformations who developed severe thrombosis in the perioperative period following surgical repair. The mutations and polymorphisms included in the study were Factor V Leiden, prothrombin G20210A, methylentetrahydrofolate reductase C677T, endothelial nitric oxide synthase intron 4 VNTR, alpha-fibrinogen Thr312Ala, Factor XIII Val34Leu, and insertion or deletion of angiotensin 1 converting enzyme. Compared to the healthy Turkish subjects, our patients had a similar rate of mutation of Factor V Leiden, Factor XIII Val34Leu, and endothelial nitric oxide synthase a/b polymorphisms, but higher frequency of the prothrombotic angiotensin 1 converting enzyme deletion/deletion genotype, and lower frequency of the antithrombotic alpha fibrinogen Thr/Thr genotype. None of the patients exhibited mutations involving prothrombin G20210A or methylentetrahydrofolate reductase C677T. The results of our study suggest that, in addition to prothrombotic mutations such as Factor V Leiden, single-nucleotide polymorphisms should be considered in all children with congenital cardiac malformations who develop thrombosis. Malformations of the heart are the most common of all serious lesions that are present at birth, with an incidence of 4 to 8 cases per 1,000 live births. If needed, corrective surgery is usually the optimal treatment for these anomalies, but perioperative morbidity and mortality still remain high due to several factors. Arterial or venous thrombosis, or both varieties of thrombosis, is among these factors. Prior to surgery, the most frequent time at which these children develop thrombosis is during cardiac catheterization. Postoperative thrombosis in this group of patients is a more complex disorder, which can affect both small and large vessels, and is associated with a high morbidity and mortality. Recent studies indicate that both point mutations and single-nucleotide polymorphisms of genes that encode proteins involved in the coagulative and anticoagulative cascades are important risk factors for development of thrombosis. Patients with these risk factors are most likely to develop thrombosis when triggering elements, such as placement of catheters, prolonged immobilization, or surgery, are also present. In this study, we investigated some of the above-mentioned mutations and polymorphisms in children who developed thrombosis in the perioperative period after correction of congenital cardiac malformations.