A novel deletion involving exon 13 of factor VIII gene in a newborn with splenic hematoma.

Splenic hematoma is an exceptionally rare event in newborn period that usually occurs in concomitant birth trauma and bleeding disorder. This report presents a newborn case with severe hemophilia A, who had a splenic hematoma presented on the second day of life with severe anemia, abdominal distention, abdominal and scrotal ecchymosis. The patient was successfully treated medically with factor VIII concentrates without splenectomy. Molecular analysis of the factor VIII gene revealed a hemizygous deletion in exon 13.

Refugee children with beta-thalassemia in Turkey: Overview of demographic, socioeconomic, and medical characteristics.

AIM: Since the beginning of the Syrian civil war, more than 3.5 million Syrians have been under temporary protection status in Turkey. Because beta-thalassemia (BT) is a prevalent disorder in the Mediterranean countries, we decided to estimate the prevalence of and make an overview of the demographic, socioeconomic, medical characteristics, and healthcare problems of refugee children with BT. PATIENTS: Eighteen Turkish Pediatric Hematology Oncology Centers (PHOC) with 318 refugee children from 235 families participated in the study. The mean age of the patients was 8.1 ± 4.8 years (0.5-21 years). The mean time after immigration to Turkey was 2.5 ± 1.5 years (range, 0.1-7 years). Seventy-two (22.6%) of them were born and diagnosed with BT in Turkey. On physical examination, 82 patients (26%) were underweight and 121 patients (38%) were stunted. The appearance of a thalassemic face was reported for 207 patients (65.1%). Hepatomegaly and splenomegaly were reported in 217 (68.2%) and 168 (52.8%) patients, respectively. The median ferritin level was 2508 ng/mL (range, 17-21 000 ng/mL) at the first admission, and 2841 ng/mL (range, 26-12 981 ng/mL) at the last visit after two years of follow-up in a PHOC (P > 0.05). The most frequently encountered mutation was IVSI-110 (G>A) (31%). Before immigration, only 177 patients (55.6%) reported the use of chelators; after immigration it increased to 268 (84.3%). CONCLUSION: Difficulties in communication, finding a competent translator capable in medical terminology, nonregular use of medications, and insensitivity to prenatal diagnosis were preliminary problems. The current extent of migration poses emerging socioeconomic and humanitarian challenges for refugee patients with BT.

Impact of Prophylaxis on Bone Mineral Metabolism in Children With Hemophilia.

In this study, we aimed to investigate changes in calcium (Ca) metabolism in hemophilia patients (PWH). We also aimed to investigate the importance of diagnosis and treatment of factors impairing calcium metabolism and the significance of early diagnosis and prophylaxis with respect to these subjects. For all patients, serum calcium, phosphorus, alkaline phosphatase, 25 hydroxy vitamin D (25-OHD), parathormone (PTH), and calcitonin levels were evaluated. Bone mineral density (BMD) was assessed by dual-energy x-ray absorptiometry. Low BMD scores and 25-OHD deficiency were observed in 29 (74.4%) and 34 (87.2%) patients, respectively. Prophylaxis of PWH did not differ significantly in terms of 25-OHD levels and BMD scores. Patients in the prophylaxis group had significantly higher PTH levels (P=0.042). A negative correlation was found between PTH measurements and Z-score (P=0.008). In summary, our findings, with a small number of PWH in our study group, suggest that biochemical markers of bone turnover may be used to detect bone loss. Follow-up through annual BMD measurements coupled with appropriate exercise programs could be recommended.

A De Novo Heterozygous Variant (HBB: c.379delG, p.Val127Cysfs*32) Associated with a Mild ß-Thalassemia Intermedia Phenotype in a Turkish Child.

We report a de novo heterozygous variant of the ß-globin chain that showing a mild ß-thalassemia intermedia (ß-TI) phenotype. He presented with mild anemia, splenomegaly, reticulocytosis, and poikilocytosis and tear drop cells on the blood smear; Immune mediated hemolysis, red cell membrane and enzyme defects, were excluded; hemoglobin (Hb) electrophoresis showed an elevation of Hb F. Molecular analysis of the ß-globin gene showed a heterozygous variation in exon 3 (HBB: c.379delG, p.Val127Cysfs*32) in the absence of an α-globin gene mutation or mutations that modulate Hb F expression.

Granulocyte transfusions in the management of neutropenic fever: A pediatric perspective.

Severe neutropenia-associated invasive bacterial or fungal infections are still the major cause of mortality and morbidity in children receiving cancer chemotherapy. Granulocyte transfusion therapy has been used for many years in the management of neutropenic patients with severe infections in whom the clinical condition deteriorated despite appropriate antimicrobial treatment. Transfused granulocytes can increase the recipient's blood neutrophil count and accumulation of them into the site of infection. There are some data obtained from retrospective or prospective observational studies in pediatric granulocyte transfusion therapy, but results are not conclusive. This review appraises the potential benefits and risks of the use of granulocyte transfusion in children with neutropenic fever.

Two versus three day upfront use of granulocyte-colony stimulating factor in healthy bone marrow donors for pediatric bone marrow transplantation.

In order to decrease donors' exposure to granulocyte-colony stimulating factor (G-CSF), we compared the effect of two versus three days of G-CSF priming on CD34+ yield in bone marrow (BM) harvest. Although the number of BM-CD34+ cells was higher in 3day G-CSF priming, we achieved the same number of CD34+ cells per recipient's weight in 2day G-CSF priming group, too. In addition, the number of total nucleated cells (TNC) harvested from BM were similar with two or three day regimen. But mononuclear cells (MNC) of the BM graft was higher in the 3day G-CSF priming group. Similar to CD34+ cell numbers, BM harvest yielded similar TNC, and MNC numbers per kilogram of the recipient. We also found that, young donors (≤10year) had more peripheral blood MNC, bone marrow MNC and CD34+ cell numbers. Another interesting finding of this study was obtaining adequate number of peripheral blood stem cells for leukapheresis with three day G-CSF administration. Since engrafment times were also similar in two groups, we concluded that 2-days G-CSF priming was resulted in sufficient mobilization of BM stem cells.

Switching from Deferasirox Dispersible Tablets to Deferasirox Film-Coated Tablets: Is There an Effect on Ferritin Levels in Children and Adolescents with Transfusion-Dependent Anemia?

OBJECTIVE: To investigate the effect of switching from deferasirox dispersible tablet (DT) to deferasirox film-coated tablet (FCT) on serum ferritin (SF) levels in transfusion-dependent patients. MATERIALS AND METHODS: Patients who received regular erythrocyte transfusion and whose treatment was switched from DT to FCT were included in the study. FCT start date was taken as the index date. Patients were followed over 2 equal and long periods, both before and after index date. RESULTS: Thirty-two patients were included, and the comparison periods ranged from 4 to 12 months. The SF values increased from a median of 1723 ng/mL (range 717-5369 ng/mL) to 1.853 ng/mL (range 924-5478 ng/mL) after switching from DT to FCT (P = .036). While there was a significant increase in median SF after switching in Turkish patients (1467 ng/mL to 1778 ng/ mL, P = .010) and patients ≥12 years (1598-1848 ng/mL, P = .009), there was an insignificant (P = .859) decrease in SF in immigrant children. Considering only the post-switch period, there was a non-significant increase in median SF in the entire cohort, while SF decreased significantly in immigrant children (P = .026). No serious side effects were observed in any patient that would cause discontinuation of treatment. CONCLUSION: Overall, higher SF value was observed with FCT compared to DT in short term. There were different results between patient groups. Our results suggest that FCT is more effective than DT in patients with high basal ferritin and who are actually incompatible with treatment and should be preferred first in these patients.

The Role of FDG- PET/CT in Detecting Bone Marrow Involvement in Childhood Solid Tumors.

PURPOSE: To compare the results of 18F-Fluorodeoxy positron emission tomography/computed tomography (18 F-FDG-PET/CT) and bone marrow biopsy (BMB) procedures in the initial evaluation of bone marrow involvement (BMI) in pediatric solid tumors. METHODS: We conducted a retrospective analysis of newly diagnosed pediatric cases with lymphoma, neuroblastoma, Ewing sarcoma, rhabdomyosarcoma. Each case underwent both PET-CT imaging and BMB. Presence of tumor infiltration in BMB specimens and/or positive FDG-PET/CT findings indicate as BMI were regarded as true positive results. RESULTS: Sixty-four patients were included in the study. BMI was detected in 23/64 (36%) patients, FDG-PET/CT imaging and BMB results were concordant in 54/64 patients. In 9/64 patients the finding was FDG-PET/CT (+), BMB (-) indicating a false negative BMB result. In only 1/64 patients FDG- PET/CT (-), BMB (+), indicating a false negative FDG-PET/CT result. In the whole patient group, the sensitivity, specificity, positive predictive value and negative predictive value of PET/CT and BMB in detecting bone marrow involvement were 95.6%, 100%, 100% and 97.6% and 60.8 %, 100%, 100% and 82%, respectively. CONCLUSION: PET/CT has a high sensitivity and specificity for the assessing marrow involvement in pediatric solid tumors. We believe that PET/CT imaging should be performed as the first step in diagnostic staging, and BMB may not be necessary in every patient, only in patients with suspicious PET/CT results for bone marrow involvement. Additionally, for a more precise determination of bone marrow involvement, it is reasonable to perform BMB from FDG-retaining areas, using PET/CT as a guide tool.

Isocitrate Dehydrogenase 1 and 2 Mutations in Pediatric Neuroblastoma Patients.

Objective: Neuroblastoma is one of the common tumors of childhood. The demonstration of new factors such as isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) mutations will be important in the diagnosis and treatment. IDH1 and IDH2 mutations have been found in many types of cancer, such as malignant gliomas, acute myeloid leukemias, chondrosarcoma, and thyroid carcinoma. This study aimed to investigate the presence of IDH1 or IDH2 mutations in patients with neuroblastoma and to determine whether these mutations were different in terms of age, clinical findings, and response to treatment. Methods: Biopsy specimens of 25 patients with pediatric neuroblastoma patients were evaluated for IDH mutations. The clinical and laboratory features of the patients with/without mutation were retrospectively analyzed from a hospital database. Results: A total of 25 patients for whom genetic analysis could be performed were included in the study (60% male, n=15). The mean age was 32.2±25.9 months (3 days-96 months). IDH1 mutation was detected in 8 (32%) and IDH2 mutations in 5 (20%) patients. These mutations showed no statistically significant relationship with age, tumor localization, laboratory results, stage, and prognosis. However, in the case of IDH mutation, patients were diagnosed at the advanced stage. Conclusions: This study demonstrated the relationship between neuroblastoma and IDH mutation for the first time. Because to the fact that the mutation is very heterogeneous, it would be appropriate to conduct a larger series of patients in terms of the impact of the clinical significance of each mutation on the diagnosis and prognosis.

Imerslund-Gräsbeck Syndrome presenting with microangiopathic hemolytic anemia in a child.

Imerslund-Gräsbeck Syndrome is a rare autosomal recessive disorder characterized by proteinuria and selective malabsorption of cobalamin. Deficiency of cobalamin can lead to megaloblastic anemia, pancytopenia and even "pseudo"-thrombotic microangiopathy (TMA). Signs of mechanical hemolysis on peripheral blood smear, elevated lactate dehydrogenase and thrombocytopenia are common findings of TMA. We report a child presenting with TMA features with cobalamin deficiency. Because of her family history of vitamin B12 deficiency and proteinuria, the performed genetic analysis revealed that an Imerslund-Gräsbeck Syndrome with the detection of a homozygous mutation in AMN gene.

Are the methylenetetrahydrofolate reductase 1298 and 677 gene polymorphisms related to optic glioma and hamartoma risk in neurofibromatosis type 1 patients?

The methylenetetrahydrofolate reductase (MTHFR) gene plays a key role in carcinogenesis through its effects on DNA synthesis and methylation and also has a significant role in the etiology of many disorders, such as diabetes, migraine, and cardiovascular disease. Neurofibromatoses (NF) are autosomal dominant inherited diseases that can affect tissues such as bone and skin and predispose individuals to tumor development in various parts of the nervous system or body. Optic nerve glioma and brain tumors are common in children with NF, and leukemia and lymphoma incidence is also higher than normal. We therefore aimed to investigate the possible relationship between the MTHFR gene polymorphism and accompanying tumors such as neurofibroma, hamartoma, and optic glioma in children with NF1 found to have the MTHFR 677 and MTHFR 1298 gene polymorphism in this study. We included 55 pediatric patients diagnosed with NF1 between 2005 and 2014 in the study group. The control group included 44 healthy subjects without acute or chronic disease findings. A significant relationship was found between the MTHFR A1298C polymorphism and the incidence of optic glioma (p=0.014) (AA vs. AC: OR 11, 95% CI 1.27-95.17; AA vs. CC: OR 7.33, 95% CI 0.35-150.70). We also found a significant relationship between the MTHFR C1298C polymorphism and the incidence of hamartoma (p=0.019) (AA vs. AC: OR 2.12, 95% CI 0.662-6.809; p=0.203). Epilepsy incidence was high in subjects with MTHFR C677C. The MTHFR A1298C, C1298C, and C677C gene polymorphisms can be associated with a higher optic glioma, hamartoma, and epilepsy incidence, respectively, in patients diagnosed with neurofibromatosis type 1.

The relationship between pulmonary function tests, thorax HRCT, and quantitative ventilation-perfusion scintigraphy in chronic obstructive pulmonary disease.

We have evaluated the relationship between pulmonary function tests (PFT), thorax high resolution computed tomography (HRCT) images and quantitative ventilation-perfusion (V/Q) scintigraphic studies in 16 male patients (mean age 65.6 +/- 5.5 years) with chronic obstructive pulmonary disease (COPD). The mean forced vital capacity (FVC) value of the patient group was 2352 +/- 642 mL (65.4 +/- 15.8%), whereas mean forced expiratory volume in one second (FEV(1)) was found to be 1150 +/- 442 mL (40.8 +/- 14.9%). The ratio of carbon monoxide diffusion capacity to alveolar ventilation (DLCO/VA) was 3.17 +/- 0.88 mL/min/mmHg/L, and the mean partial oxygen (PaO(2)) and carbon dioxide (PaCO(2)) pressures were 68.5 +/- 11.04 mmHg and 38.9 +/- 5.8 mmHg respectively. For each patient, thorax HRCT and V/Q scintigraphic images of both lungs were divided into upper, mid and lower zones during examination. Visual scoring for the assessment of emphysema on thorax HRCT were used and images were graded from mild to severe (< or = 25% - > or = 76%). Emphysema scores were found to be higher on upper zones with accompanying lowest V/Q ratios. DLCO/VA, DLCO, total emphysema scores, and individual emphysema scores of the upper, mid and lower zones were found to be correlated. As a conclusion, it can be stated that emphysematous changes in COPD patients are more apparent in the upper lung zones, which also have the lowest V/Q ratios.