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Background: Acute myeloid leukemia (AML) is the second most common leukemia accounts for 20% of childhood leukemia. Intensive chemotherapy and hematopoietic stem cell transplantation (HSCT) improve outcomes. In this study, it was aimed to present the clinical features and treatment results of patients diagnosed with pediatric AML in the last three years. Methods: It is an observational clinical study, patients who received chemotherapy and HSCT with the diagnosis of AML between 2018 and 2020 were retrospectively evaluated. Age, gender, AML subtype, genetic characteristics, laboratory findings, treatment responses, febrile neutropenia and fungal infection frequencies of the patients were evaluated. HSCT indications, pre-transplant bone marrow aspiration results, transplant type, donor characteristics, and post-transplant complications of patients who underwent HSCT were recorded. Post-treatment status and treatment success rates of the patients were evaluated. Results: Of the 46 patients included in the study, 26 were female and 20 were male. The mean age was 8.2 ± 5.75 years. The most common subtypes were AML M4 and M5 with 9 patients. Total of 201 febrile neutropenia attacks were observed. Suspicious or definite proven Aspergillus infection was detected in 20 of the patients. HSCT was applied to 27 of the patients. Four patients were Down syndrome-myeloid leukemia (DS-ML) and FLT3-ITD mutation was detecetd in 5 patients. Conclusions: FLT3-ITD mutation, relapse disease, and pre-HSCT M2 bone marrow were found to be highly correlated with progressive disease and mortality. In addition, patients with Down syndrome had a high mortality due to additional comorbidity and drug adverse effects.

Standard of care (SOC) anticoagulation for thromboembolism (TE) prevention in children with cardiac disease includes low molecular weight heparins or vitamin K antagonists. Limited data exists for alternate use of direct oral anticoagulants in children.The investigators aimed to obtain safety and efficacy data for edoxaban in children.We performed a phase 3, multinational, prospective, randomized, open-label, blinded-endpoint trial in patients 18 years of age with cardiac disease (ENNOBLE-ATE [Edoxaban for Prevention of Blood Vessels Being Blocked by Clots (Thrombotic Events) in Children at Risk Because of Cardiac Disease] trial). Patients were randomized 2:1 to age- and weight-based oral edoxaban once daily vs SOC for 3 months (main study period), stratified by cardiac diagnosis. Both groups could continue in an open-label edoxaban extension arm through 1 year. The primary endpoint was adjudicated clinically relevant bleeding (CRB). The main secondary endpoint was symptomatic TE or asymptomatic intracardiac thrombosis.The modified intention-to-treat cohort included 167 children. One patient per group experienced a nonmajor CRB in the main period. Treatment-emergent adverse events occurred in 46.8% (51 of 109) with edoxaban and 41.4% (24 of 58) with SOC. One SOC patient experienced 2 TE events (DVT with PE). Among 147 children in the extension, 1 CRB event (0.7%) and 4 TEs occurred (2.8%; 2 strokes and 2 of 33 Kawasaki disease patients with coronary artery thromboses and/or myocardial infarctions).Edoxaban is a potential alternative mode of thromboprophylaxis in children with cardiac disease showing low rates of CRB and TEs with advantages of once daily dosing and infrequent monitoring requirement. (ENNOBLE-ATE [Edoxaban for Prevention of Blood Vessels Being Blocked by Clots] (Thrombotic Events) in Children at Risk Because of Cardiac Disease trial; NCT03395639).

Background: Data on the outcome and risk factors of pediatric patients with SARS-CoV-2 infection (COVID-19) following hematopoietic stem cell transplantation (HSCT) are limited. Objectives: We aimed to describe risk factors for a severe course and mortality. Method: In this nationwide study, data were collected retrospectively from 28 transplant centers. Results: One hundred ninety-six children [(63.8% male; median age 8.75 (IQR, 4.86-14.30)] who received allogeneic (n: 184, 93.9%) or autologous (n: 12, 6.1%) HSCT were included. The median time from HSCT to SARS-CoV-2 infection was 207.5 days (IQR, 110.2-207.5). The most common clinical manifestation was fever (58.2%), followed by cough (33.7%); 43 cases (21.9%) were asymptomatic. Lower respiratory tract disease (LRTD) and multisystem inflammatory syndrome in children (MIS-C) developed in 58 (29.6%) and 8 (4.1%) patients, respectively. Twenty-six patients (13.3%) required ICU admission. Nine patients died at a median of 17 days (min-max 1-33) after COVID-19 diagnosis, 6 of whom died due to the disease, with a COVID-19 lethality rate of 3.1%. The 6-week overall survival was 95.4% (95% CI 92.5-98.3). Multivariate analysis found that HSCT with a mismatched donor (OR, 8.98, p: 0.039) and LRTD (OR, 61.55, p: 0.001) were independent risk factors for ICU admission; MIS-C (OR, 9.55, p: 0.044) and lymphopenia (OR, 4.01, p: 0.030) at diagnosis were risk factors for mortality. Conclusion: Overall mortality was lower in children than in adult counterparts, and HSCT with a mismatched donor, lymphopenia, LRTD, MIS-C and ICU admission were important risk factors for adverse outcomes.

Hepatitis-associated aplastic anemia (HAA) is a form of acquired aplastic anemia (AA) in which bone marrow failure develops after an acute attack of hepatitis. Bone marrow failure leading to AA is generally severe in cases of HAA and fatal if left untreated. This retrospective multicenter study investigated clinical and laboratory characteristics, possible causes, treatment, and outcome of HAA in children. Twenty patients from 8 centers were included in the study. Aspartate aminotransferase and alanine aminotransferase were 10×ULN in 16 patients. Acute liver failure developed in 5 (29%) patients. Pancytopenia was simultaneously present in 6 of 20 (30%) patients. Eleven of the 20 patients (55%) were alive, in remission and transfusion free. Those who were alive either had undergone hematopoietic stem cell transplantation and/or immunosuppressive treatment, except 1 patient who had received no treatment. Patients with the diagnosis of acute hepatitis should be evaluated and followed up carefully for presence of cytopenia, so that definitive treatment of AA can be initiated in a timely and appropriate manner when needed. Copyright r 2021 Wolters Kluwer Health, Inc. 34669357

Leukocyte adhesion deficiency is an autosomal recessive primary immunodeficiency that has been divided into three types: LAD1 (beta-2 integrin (CD18) family deficiency/defect), LAD2 (absence of fucosylated carbonhydrate ligands for selectins) and LAD3 (defective activation of all beta integrins). However, recently LAD4 has been described in cystic fibrosis patients, with a defect in integrin activation reported in monocytes. LAD-I is the most common type and prevalence of 1 in 1,000,000 live births. Clinical features of LAD patients are recurrent bacterial and fungal infections, omphalitis with delayed umbilical stump separation, significant leukocytosis especially neutrophilia during infection periods, impaired pus formation, and delayed traumatic or surgical wound healing. Flow cytometry is considered a useful tool for rapid diagnosis of the disease. The study of CD18 and CD11 (a, b, c) expression patterns in peripheral blood leukocytes helps to distinguish different phenotypes of LAD-I. In general, patients with >= 2% CD18 expression tend to have a less severe infection and often survive until adulthood, whereas < 2% CD18 expression often results in death in infancy. In this case report, three siblings, 10, 15, and 17 years old, diagnosed with leukocyte adhesion defect type 1 in adolescence age group, are presented.

Since little is known about dysregulated hyperinflammatory immunological responses causing acute severe infection and multisystem inflammatory syndrome in children associated with coronavirus disease 2019 (COVID-19), the available data on therapies for severe presentations in children are very limited. Describing experiences of severe pediatric COVID-19 presentations in more detail will help improve clinical practice.In this case report, we describe the complete clinical course of a 9-year-old girl previously diagnosed with Angelman syndrome and high-risk T cell acute lymphoblastic leukemia who had been receiving reinduction chemotherapy, presented with pneumonia and acute respiratory distress syndrome, and progressively developed hyperferritinemic multiple-organ failure, a cytokine storm, and coagulopathy associated with COVID-19. She was treated with therapeutic plasma exchange, tocilizumab, hydrocortisone, and favipiravir, but she died 7 days after her admission into our pediatric intensive care unit.The utility of therapeutic plasma exchange with other immunomodulatory therapies in severe presentations requires further trials. The spectrum of the inflammatory phenotypes associated with COVID-19 should be investigated and well defined to initiate the optimal treatment strategy on time.

Spontaneous colonic cast excretion per anus is a very rare entity. Colonic ischemia and severe infections are the most common etiologic factors. It is mostly seen in adults. Only one pediatric patient with colonic cast excretion was reported in the literature. We present a three-year-old male patient with the diagnosis of neuroblastoma who had undergone autologous BMT. After suffering a prolonged rotavirus infection, on the 25th the post-transplantation day, he presented with nausea, vomiting, abdominal pain, and spontaneous excretion of colonic mucosa-like material via defecation. The histopathological interpretation of the excreted material revealed acellular material composed of fibrin and neutrophils. The patient’s colonoscopic biopsy specimen revealed crypt distortion, regeneration, and numerous apoptotic bodies within the crypt epithelium. Apoptotic colopathy and colonic cast excretion per anus is a sign of ischemia, which may be caused by severe intestinal infections or rarely, graft-versus-host disease. Therefore, a clinicopathological correlation was performed to reach a definitive diagnosis. The patient’s symptoms were attributed to severe, prolonged rotavirus infection.

Different and various system complications and late effects may occur after hematopoietic stem cell transplantation (HSCT). It was aimed to obtain information about the frequency of ophthalmologic complications and their relationship with treatment. This retrospective study includes 104 children who underwent HSCT between February 2019 and June 2020 at the Pediatric Bone Marrow Transplant Unit. Patients' ages, genders, diagnosis, transplant types, chemotherapy regimens, transplantation details, conditioning regimens, supportive cares, graft versus host disease (GvHD) prophylaxis, infection episodes, and ophthalmologic findings were evaluated. Of the 104 patients included in the study, 38 (36.5%) were female and 66 (63.5%) were male. Average age ± SD was 8.7 ± 4.91. Considering the diagnoses, the majority of the patients were acute lymphoblastic leukemia (46 patients-44%). Myeloablative regimen was used in 93 (89%) of the patients, and reduced intensity conditioning (RIC) was used in 11 patients (10%). While total body irradiation was applied in 16 (15%) patients, one patient was received cranial radiotherapy. Cyclosporine was used in 96 (92%) patients. CMV reactivation was detected in 54 (51%) of the patients. CMV retinitis was not seen. Ocular pathology was detected in 20 (19%) patients before HSCT and in 12 (11%) patients after HSCT. The most common pathology was dry eye. Routine ophthalmologic examinations are important in terms of early diagnosis. In addition, GvHD and CMV prophylaxis is important because of reducing the risk of ocular complications after HSCT.

The aim of the study was to analyze the characteristics of posterior reversible encephalopathy syndrome (PRES) cases treated at 10 different institutions in our country. Fifty-eight patients diagnosed with PRES were included in this study. The data of PRES cases from 10 departments of pediatric hematology/oncology were analyzed. The mean age of the patients at the time of diagnosis of PRES was 8.95 +/- 3.66 years. Most patients (80.4%) had a primary diagnosis of acute leukemia. Patients received chemotherapy (71.4%) and/or used steroids within 14 days before the diagnosis of PRES (85.7%). Hypertension was found in 83.9% of the patients. Twenty-six patients had infections and 22 of them had febrile neutropenia. The most common electrolyte disorders were hypocalcemia, hypomagnesemia, and hypopotassemia. Six patients had tumor lysis syndrome and 4 had inappropriate antidiuretic hormone syndrome. Magnetic resonance imaging was used for diagnosis in all patients. The most commonly involved regions by magnetic resonance imaging were occipital (58%), parietal (51%), and frontal lobes (45%), respectively. Twenty-five patients required intensive care and 7 patients were intubated. In conclusion, PRES may develop during the follow-up and treatment of hematological diseases. In addition to steroid and intense combined chemotherapies, immunosuppressive agents and hypertension are also factors that may be responsible for PRES.

Giriş: Anemi düşük kan hemoglobin konsantrasyonu olarak tanımlanır ve Dünya Sağlık Örgütü (WHO) tarafından küresel anemi prevalansı % 24.8 kadar yüksek bir oranda bildirilmektedir. Günümüzde ise sağlık sistemleri artan mülteci nüfusuyla ve bunların karşılaşacağı sağlık problemleri ile karşı karşıyadır. Bu çalışmanın amacı, göçmen ve mülteci nüfusa hizmet eden hastanemize başvuran çocuk hastalardaki anemi varlığını tesbit etmektir. Yöntem: Çalışma geriye dönük olarak 2012-2018 yıllarını kapsayacak şekilde herhangi bir nedenle Tepecik Eğitim ve Araştırma Hastanesi Çocuk Kliniklerine başvuran 0-18 yaş arası göçmen ve mülteci hastanın değerlendirilmesi yapıldı. Herhangi bir nedenle hastaneye giriş yapan ve hematolojik parametreleri kodlanan hastalar çalışmaya dahil edildi. Bulgular: Toplam 2234 (%46.2) kız olmak üzere 4840 olguya ulaşıldı. Olguların 4793 (%99,0)’ü Suriyeli idi. Ortalama başvuru yaşları 47, 67 ± 57,79 (0-226) ay bulundu. Ortalama Hb değeri 10, 8 ± 1,5, ortalama Hct 32,8 ± 4,3, ortalama MCV 75,9 ± 9,6 ve ortalama RDW 14,9 ± 2,5 saptandı. Ortalama demir değeri 46,41 ± 36,6, demir bağlama kapasitesi (DBK) 379, 52 ± 75,98, transferrin satürasyonu 11,95 ± 9,7 ortalama ferritin değeri ise 94,5 ± 452 olarak hesaplandı. Hb değeri 10 ve altında olan toplam 331 (%6,8), 8 ve altında olan ise 83 ( %1,71) olgu vardı. MCV değeri yaşa göre alt sınırda olan olguların demir eksikliği parametrelerini değerlendirmek amaçlı Menzter, Shine& Lal ve England indeksleri hesaplandı. MCV alt sınırda olup Menzter indeksi >13 olan olgular toplam 1525 idi (714 (%46,8) kız). Bunlarda MCV ile DBK arasında (p= 0,033, korelasyon katsayısı -0,124) ve TS arasında (p= 0,000, korelasyon katsayısı 0,232) anlamlı ilişki vardı. MCV alt sınırda olup Shine > 1530 olan toplam 1934 (886 kız) vardı ve MCV ile hiçbir demir parametresi arasında ilişki bulunmadı. England > 0 olan olguların ise sayısı 1277 idi ve sadece MCV ile TS satürasyonu arasında ilişki bulundu (p= 0,001 ve korelasyon katsayısı 0,223)Tartışma: Her ne kadar çalışmamız geriye dönük olsa ve bir çok veri eksiği içerse de anemi oranını bu popuülasyonda saptamış olması açısından dikkat çekicidir.

Immune thrombocytopenia (ITP) is a rare autoimmune disease and hematologic disorder characterized by reduced platelet counts that can result in significant symptoms, such as bleeding, bruising, epistaxis, or petechiae. The thrombopoietin receptor agonist eltrombopag (EPAG) is a second-line agent used to treat chronic ITP purpura in adults and children.The present retrospective study evaluated the efficacy, safety, and side effects of EPAG treatment in pediatric patients with acute refractory and chronic immune thrombocytopenia, particularly focusing on iron-deficiency anemia.The diagnosis was chronic ITP in 89 patients and acute refractory ITP in 16 patients. The mean age of patients was 9.5±4.5 years (minimum-maximum: 1.2-18 years) at the beginning of EPAG treatment. The overall response rate was 74.3% (n=78). The mean time for platelet count of ≥50x109/L was 11.6±8 weeks (range: 1-34 weeks). The treatment was stopped for 27 patients (25.7%) at an average of 6.8±9 months (range: 1-38 months). The reason for discontinuation was lack of response in 18 patients, nonadherence in 4 patients, and hepatotoxicity in 2 patients. Response to treatment continued for an average of 4 months after cessation of EPAG in 3 patients.Results of the current study imply that EPAG is an effective therapeutic option in pediatric patients with acute refractory and chronic ITP. However, patients must be closely monitored for response and side effects during treatment, and especially for iron deficiency.İmmün trombositopeni (İTP) nadir otoimmün bir hastalık olup, platelet sayısındaki azalmaya bağlı olarak peteşi, ekimoz, epistaksis gibi kanama semptomları ile karakterizedir. Trombopoietin reseptör agonisti eltrombopag (EPAG), yetişkinlerde ve çocuklarda kronik immün trombositopeni tedavisinde kullanılan ikinci basamak bir ajandır.Bu retrospektif çalışma, akut refrakter ve kronik immün trombositopenili çocuk hastalarda EPAG tedavisinin etkinliğini, güvenilirliğini, yan etkilerini özellikle de demir eksikliği anemisi gelişimini değerlendirmiştir.Hastalarımızın 89’u kronik İTP, 16’sı ise akut refrakter İTP tanısı ile takip edilmekte idi. Tedavi başlangıcı sırasında hastalarımızın yaş ortalamaları 9,5±4,5 yıl (1,2-18 yıl) idi. Toplam yanıt oranımız %74,3 (n=78) idi. Platelet sayısının ≥50x109/L olması için geçen ortalama süre 11,6±8 hafta (1-34 hafta) idi. Tedavi 27 hastamızda (%25,7) ortalama 6,8±9 ayda (1-38 ay) kesildi. Tedavi kesim nedenlerimiz; 18 hastada yanıtsızlık, 4 hastada tedaviye uyumsuzluk, 2 hastamızda ise hepatotoksisite idi. Üç hastada ise EPAG tedavisi kesilmesinden sonra yanıt ortalama 4 ay devam etti.Çalışmamız, EPAG tedavisinin akut refrakter ve kronik İTP’li pediyatrik hastalarda etkili bir terapötik seçenek olduğunu göstermektedir. Bununla birlikte, hastalar EPAG tedavisi sırasında yanıt ve yan etkiler ve özellikle demir eksikliği açısından yakından izlenmelidir.

EgeUn###, Allergic bronchopulmonary aspergillosis is an immunologic pulmonary disorder caused by hypersensitivity to Aspergillus fumigatus. This disorder is most commonly seen in patients with poorly controlled asthma and cystic fibrosis. It is rarely reported in chronic granulomatous disease patients; however, there are no cases reported with hematopoietic stem cell transplantation in the English literature. Herein, we report a patient with chronic granulomatous disease who had hematopoietic stem cell transplantation and subsequently developed allergic bronchopulmonary aspergillosis.

Additional file 1: Table S1. Number of measurements for male and female patients for height, weight and head circumference in relation to the age groups.

PurposeMowat-Wilson syndrome (MWS) is a rare intellectual disability/multiple congenital anomalies syndrome caused by heterozygous mutation of the ZEB2 gene. It is generally underestimated because its rarity and phenotypic variability sometimes make it difficult to recognize. Here, we aimed to better delineate the phenotype, natural history, and genotype-phenotype correlations of MWS.MethodsIn a collaborative study, we analyzed clinical data for 87 patients with molecularly confirmed diagnosis. We described the prevalence of all clinical aspects, including attainment of neurodevelopmental milestones, and compared the data with the various types of underlying ZEB2 pathogenic variations.ResultsAll anthropometric, somatic, and behavioral features reported here outline a variable but highly consistent phenotype. By presenting the most comprehensive evaluation of MWS to date, we define its clinical evolution occurring with age and derive suggestions for patient management. Furthermore, we observe that its severity correlates with the kind of ZEB2 variation involved, ranging from ZEB2 locus deletions, associated with severe phenotypes, to rare nonmissense intragenic mutations predicted to preserve some ZEB2 protein functionality, accompanying milder clinical presentations.ConclusionKnowledge of the phenotypic spectrum of MWS and its correlation with the genotype will improve its detection rate and the prediction of its features, thus improving patient care.GENETICS in MEDICINE advance online publication, 4 January 2018; doi:10.1038/gim.2017.221. ispartof: Genetics in Medicine vol:20 issue:9 pages:965-975 ispartof: location:United States status: published

Objectives: Ophthalmologic disease in patients with acute leukemia occurs due to primary leukemic infiltration (involvement), or secondary to the disease and its treatment. In recent years the life expectancy of acute leukemia patients has increased with the advent of modern therapies. The present study aimed to determine the incidence of ocular manifestations in children with acute leukemia. Materials and Methods: The study included 120 patients diagnosed with acute leukemia at Baskent University Hospital, Pediatric Hematology Department between 1995 and 2010. All the patients were examined by an ophthalmologist via direct and indirect ophthalmoscopy. Results: Among the patients, 83 (69.2%) were diagnosed with acute lymphoblastic leukemia, 35 (29.1%) with acute myeloblastic leukemia, and 2 (1.7%) with mixed-lineage leukemia. In all, 58 ophthalmic manifestations were noted in 41 patients (34.2%). In our patients, 12 ophthalmologic involvements were present at admission and 46 ocular findings occurred during follow-up. The incidence of these manifestations increased with age. Conclusion: Ophthalmologic manifestations were not correlated with gender, hematological parameters at disease onset, type of leukemia, or the frequency of relapse and survival. To more clearly determine the effect of ophthalmologic manifestations on the prognosis of leukemia, larger scale and multi-center studies are needed.

Hemophilia A is an X-linked recessive disorder characterized by congenital deficiency of factor VIII. Mostly, males are affected. Cases of hemophilia A are unusual in females but can result from certain genetic mechanisms. The severity of bleeding in hemophilia is generally correlated with the coagulation factor level. In mild hemophilic cases or carriers, bleeding is not usually seen and may occur following trauma or surgery. In this report, we present a female premature newborn with psoas hematoma having a novel heterozygous missense mutation for hemophilia A. Keywords: Hemophilia A carrier, Novel mutation, Prematurity, Female, Psoas hematoma

Background: General characteristics and responses to treatment of patients with solid tumors were investigated.Methods: Patients treated with a diagnosis of solid tumors in the pediatric hematology and oncology clinic between March 2019 and June 2020 were included in the study. The gender, age, diagnosis, age of diagnosis, risk status, stage, treatment details, and treatment complications of the patients were evaluated. The risk status of the patients was determined according to the stage of each diagnosis, metastasis status and treatment protocol. It was noted whether the patients had undergone surgery or not, and patients who were in-operable were specified. Patients receiving radiotherapy were specified. The chemotherapeutic drugs given to the patients according to the treatment protocols were indicated one by one. Treatment complications or morbidity states were recorded.Results: Out of the 31 patients evaluated, 10 (32%) were female and 21 (68%) were male. The mean±SD age was 6.3±5.16 years. The youngest patient was 3 months old, and the oldest patient was 18 years old. The central nervous system was the most commonly affected area and 7 (22%) of the patients had various CNS tumors. The second most common malignancy is neuroblastoma; 4 patients (12%). Rhabdomyosarcoma and retinoblastoma were the third most common malignancy with 3 patients each. Surgical resection was performed in 19 (61%) patients. Radiotherapy was applied to 13 of the patients (41%).Conclusions: Early diagnosis and detection of the disease at low stage, complete tumor resection are important for the success of treatment.

Background Ifosfamide (IFO) is an alkylating agent used to treat broad range of malignancies. One of the life-threatening toxic effects is reversible neurotoxicity. In this report; we presented a case report of ifosfamide induced encephalopathy (IIE) in a child with osteosarcoma in order to emphize that it is important to continue ifosfamide treatment as well as the importance of this potentially fatal complication. Case report Following the 20th week of ifosfamide treatment, the patient's follow-up with the diagnosis of osteosarcoma developed neurological findings. Laboratory analyzes before and after ifosfamide infusion were normal. No pathological findings were seen on MR imaging. Hypoglycemia, electrolyte disturbances, encephalitis, meningitis, metastasis and posterior reversible encephalopathy syndrome (PRES) were not considered. Electroencephalography was found compatible with neuronal hyperexcitability originating from the left hemisphere. With the diagnosis of ifosfamide induced encephalopathy, prophylaxis with methylene blue was received before the next infusion of ifosfamide. Neurological findings were not observed in the patient's follow-up. Conclusion Patients who develop IIE can continue their treatment protocol with methylene blue prophylaxis and supportive therapy.

PubMedID: 30706992 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. © 2019 Wiley Periodicals, Inc.

The presence of lupus anticoagulants (LAs) is an important cause of activated partial thromboplastin time (aPTT) prolongation found in children after an infection or during screening tests before surgical intervention. The authors retrospectively reviewed the charts of 68 patients who have been consulted from surgery departments with prolonged aPTT. These patients were reevaluated with aPTT analysis after 1 week. Thirteen patients had normal aPTTs. Therefore, 55 patients remained with prolonged aPTTs. LA positivity was detected in 39 patients. Sixteen of these had prolonged aPTT prior to surgery (41%). Others with LA positivity had systemic lupus erythematosus (SLE; n = 6), infection (n = 5), leukemia (n = 3), hemolytic uremic syndrome (n = 2), epistaxis (n = 2), antiphospholipid syndrome (APS; n = 1), chronic immune thrombocytopenic purpura (n = 1), acute poststreptococcal glomerulonephritis (n = 1), central nervous system (CNS) thrombosis (n = 1), and congenital heart disease (n = 1). None of the patients had bleeding history. LA positivity rarely leads to bleeding and/or thrombosis. Specific therapy is usually not needed. Further prospective multicenter studies are required to understand clinical outcomes and laboratory correlation in children with positive LA.

PURPOSE: Mowat-Wilson syndrome (MWS) is a genetic disease characterized by distinctive facial features, moderate to severe intellectual disability, and congenital malformations, including Hirschsprung disease, genital and eye anomalies, and congenital heart defects, caused by haploinsufficiency of the ZEB2 gene. To date, no characteristic pattern of brain dysmorphology in MWS has been defined.METHODS: Through brain magnetic resonance imaging (MRI) analysis, we delineated a neuroimaging phenotype in 54 MWS patients with a proven ZEB2 defect, compared it with the features identified in a thorough review of published cases, and evaluated genotype-phenotype correlations.RESULTS: Ninety-six percent of patients had abnormal MRI results. The most common features were anomalies of corpus callosum (79.6% of cases), hippocampal abnormalities (77.8%), enlargement of cerebral ventricles (68.5%), and white matter abnormalities (reduction of thickness 40.7%, localized signal alterations 22.2%). Other consistent findings were large basal ganglia, cortical, and cerebellar malformations. Most features were underrepresented in the literature. We also found ZEB2 variations leading to synthesis of a defective protein to be favorable for psychomotor development and some epilepsy features but also associated with corpus callosum agenesis.CONCLUSION: This study delineated the spectrum of brain anomalies in MWS and provided new insights into the role of ZEB2 in neurodevelopment.Genet Med advance online publication 10 November 2016Genetics in Medicine (2016); doi:10.1038/gim.2016.176.

WOS: 000440491800011, PubMed ID: 29391337

Among bleeding disorders, hemophilia A, hemophilia B and von Willebrand diseases are the most commonly occurring, whereas deficiencies of other coagulation factors are rare worldwide. Unlike hemophilias, which are X-chromosome linked disorders, the inheritance pattern of the rare coagulation factor deficiencies is generally autosomal recessive. In literature, association of these factor deficiencies and congenital abnormalities are especially rare. In this study, we present our cases having both rare factor deficiencies and congenital abnormalities, including Cenani-Lenz syndrome and Duane retraction syndrome.

13q deletion syndrome is caused by the absence of a portion of the long arm of chromosome 13. This syndrome is a rare condition characterized by a wide range of clinical findings. Phenotype varies with the location and size of the deletion. We report a female dizygotic twin with a proximal deletion of 13q and failure to thrive, hypotonia, and multiple anomalies included pytosis and total ophthalmology at right side, strabismus at left, bilateral iris heterochromia and telecantus. She had a broad nasal bridge with flat philtrum, micrognathia and antevert ear lobes. Her umbilicus had vanished. Her left coxa was dislocated and left toes were overlapped. She was also found to have hypertriglyceridemia, hypercholesterolemia, and hypothyroidism. Chromosome analysis showed a proximal deletion of chromosome 13 [karyotype 46,XX,del(13) (q14.2q31.3)] which was confirmed by high-resolution microarray based comparative genomic hybridization. The described patient is unique among similar rare cases with different deletion breakpoints. It is the first case of 13q14.2q31.3 deletion where the breakpoints are clearly defined, indicating the importance of detailed clinical description and high-resolution genomic analysis for characterization of rare genetic syndromes.

Asparaginase treatment is associated with several adverse effects, including allergy, thromboembolic events, acute pancreatitis, altered liver function, and hyperglycemia. In addition, asparaginase can cause abnormalities in lipid metabolism, predominantly hypercholesterolemia and -triglyceridemia. Herein, we report on the case of a 5-year-old male presenting with acute severe hypertriglyceridemia caused by accidental pegylated asparaginase push during treatment of relapsed acute lymphoblastic leukemia. Hypertriglyceridemia did not occur after appropriate administrations of pegylated asparaginase before and after accidental drug infusions, so we speculate that the rate of pegylated asparaginase administration may have an effect on the serum triglyceride level.

Posterior reversible leukoencephalopathy syndrome (PRES) is characterized by headache, altered mental status, cortical blindness, and seizures associated with neuroradiological findings. It involves predominantly white matter of the parieto-occipital lobes. Several medications and disorders play a role in the etiology of PRES. In this study, we aimed to show how the prognosis of PRES in hematological diseases of childhood might be according to the etiological factors.Here, we report PRES in six patients, aged 4 to 14 years, with diagnoses of leukemia and aplastic anemia.Suggested causes in our patients were chemotherapeutics, hypertension, infection and antimicrobial drug administration, tumor lysis syndrome, acute renal failure and hemodialysis, immunosuppressive drug administration, and hypomagnesemia. One of the patients died of sepsis, renal failure and pulmonary hemorrhage and another died of relapse after total recovery from PRES. The other four patients are under follow-up without problems.We suggest that PRES can recover fully with early diagnosis and treatment whereas it can show poor prognosis depending on the etiology.AMAÇ: Posterior geri dönüşümlü lökoensefalopati sendromu (PGDLS) nöroradyolojik bulgularla birlikte baş ağrısı, bilinç değişiklikleri, kortikal körlük ve nöbet ile seyreden bir sendromdur. Hastalık ağırlıklı olarak parieto-oksipital lobların beyaz cevherini tutar. Çeşitli ilaçlar ve hastalıklar PGDLS etiyolojisinde rol oynar. Bu çalışmada, çocukluk çağı hematolojik hastalıklarında altta yatan nedenlere göre PGDLS’nun nasıl seyrettiğini göstermeyi amaçladık. YÖNTEMLER: Burada, yaşları 4 ile 14 arasında olan, lösemi ve aplastik anemi tanıları ile izlenen PGDLS’lu 6 hastayı sunduk.Hastalarımızda kemoterapotikler, hipertansiyon, infeksiyon, antimikrobiyal ilaç kullanımı, tümör lizis sendromu, akut böbrek yetmezliği, hemodiyaliz, immünsüpresif ilaç kullanımı ve hipomagnezemiyi PGDLS nedenleri olarak tespit ettik. Hastalarımızdan birini sepsis, böbrek yetmezliği ve pulmoner hemaroji nedenleriyle, bir diğerini ise PGDLS tamamen düzeldikten sonra relaps nedeniyle kaybettik. Diğer dört hastamız herhangi bir problemi olmaksızın izlenmektedir. SONUÇ: PGDLS erken tanı ve tedavi ile tamamen düzeltilebilir bir hastalık olmasına rağmen altta yatan nedene bağlı olarak kötü seyirli de olabilen bir sendromdur.

Early detection of primary hypertension (HT) is essential to prevent the development of end organ damage, especially in patients with a family history of HT. Physicians must pay a great attention during the follow-up of these children. Our aim was to investigate whether children with hypertensive parents are under the risk of development of HT or not by using ambulatory blood pressure measurement (ABPM). Seventy-nine healthy children were enrolled in the study: 39 with positive familial history of primary HT (study group) and 40 without familial history of HT (control group). Complete blood count, urinalysis, and biochemical tests were performed in all children in the study group. Children in both groups were examined by casual BP measurement and ABPM. The study group had significantly higher levels of BP (p < 0.05) than the controls. In the study group systolic BP and diastolic BP loads were significantly higher than the controls (p < 0.000; p = 0.002, respectively). In conclusion, parental BP is a strong predictor of the future BP in their children. It is possible that early abnormalities of BP may escape from detection by casual office measurement, and ABPM is recommended especially to detect BP abnormalities before HT becomes clinically overt.

Aim: Varicella is a childhood disease, with its highest incidence being found in children aged 1 to 9 years. The aim of this study was to investigate the plasma oxidant and antioxidant status in Turkish children with varicella infection. Methods: The study population consisted of 29 children infected with varicella recruited from the Department of Pediatrics at Baskent University Hospital in Ankara, Turkey. The control group consisted of 20 age-matched children from the same region who were apparently otherwise healthy. After overnight fasting, venous blood samples were obtained and transferred to heparinized tubes. Plasma malondialdehyde and vitamin A levels were measured in both groups. Results: The plasma malondialdehyde levels were higher in children in the infected group than they were in children in the control group. However, there were no statistically significant differences in plasma vitamin A levels between the groups. Conclusion: This study suggests that oxidant stress causes significant peroxidation, and the antioxidant defence system is affected in varicella infection. Antioxidant supplementation may yield beneficial results in these patients. Further studies are needed to determine the positive effects of vitamin A supplementation in patients with varicella infections.

Recent studies have emphasized the presence of airway hyperreactivity (AHR) in children with sickle cell disease (SCD). However, various tests for the detection of AHR have yielded distinctly different results in these patients. This study identified AHR via a methacholine challenge test (MCT) in a group of children with SCD (31 patients; age range, 6-16 years). The results of pulmonary function tests (PFTs) in patients with SCD and age-matched controls (30 healthy children) were investigated and compared. A positive methacholine challenge result was noted in 25 patients (77.5%). We found that when compared with controls, the children with SCD had lower forced vital capacity (FVC) and forced expiratory volume in 1 sec (FEV(1)) and that both their forced expiratory flow at 25-75% of the FVC (FEF(25-75)) and their FEV(1)/FVC ratio were not statistically significantly different from those of the controls. The statistically significant differences remained after treatment with a bronchodilator agent, but the changes in the FVC, FEV(1), and FEF(25-75) in response to bronchodilator treatment did not differ with statistical significance between the two groups. There was a negative correlation between the number of ACS attacks and the percent predicted of the FEV(1) and the FEV(1)/FVC ratio. We found that the MCT reveals a high incidence of AHR in patients with SCD, regardless of whether those individuals have ACS.

Glukoz-6-fosfat dehidrogenaz (G6PD), eritrositlerde pentoz monofosfat yolunda görev alan, aynı zamanda hücreleri oksidatif stresten koruyan bir enzimdir.G6PD eksikliğinin en sık görülen klinik belirtileri yenidoğan sarılığı ve genellikle ilaçlar, enfeksiyonlar ve bazı gıdalar gibi eksojen ajanlar tarafından tetiklenen akut hemolitik anemidir. Bazı G6PD varyantları doğumsal non-sferositik hemolitik anemiye neden olabilirler. X’e bağlı resesif kalıtım göstermektedir. Hastalık erkeklerde ve homozigot kızlarda ortaya çıkar.Yirmi altı aylık kız olgumuz bakla yeme sonrasında göz akında sararma ve huzursuzluk şikayeti ile başvurdu. G6PD enzim eksikliği tanısı konulan hastanın babasında da GGPDH enzim düzeyi düşük saptandı. Ancak, baba defalarca bakla yeme öyküsü olmasına karşın herhangi bir hemolitik tablo gelişmemişti. Bu olgu, G6PD enzim eksikliğinin farklı cinsiyetlerde farklı klinik seyirlerinin olabileceğini vurgulamak amacı ile sunulmuştur., Glucose-6-phosphate dehydrogenase (G6PD) is an enzyme included in the pentose phosphate pathway with a cellular protective effect against oxidative stress.The most frequent clinical manifestations of G6PD deficiency are neonatal jaundice and acute hemolytic anemia, which is usually triggered by an exogenous agent such as drugs, infections and certain nutrients. Some G6PD variants cause chronic hemolysis, leading to congenital non-spherocytic hemolytic anemia. The disorder is inherited by X-linked transmission. Homozygote females and males are the cases at risk for G6PD deficiency.A 26-month-old girl presented with hemolytic anemia after eating broad beans. She was diagnosed with G6PD deficiency and interestingly the G6DP level was also decreased in her father. There was no history of hemolytic anemia in the father despite multiple exposure to broad beans. We aimed to underline the different types of clinical expressions of G6PD deficiency in different genders by presenting this case report

Adenotonsillar hypertrophy is common among children, but it can lead to serious complications if left untreated. Among the well-known complications are obstructive sleep apnea syndrome, growth failure, cor pulmonale, and hypertension. One complication of adenotonsillar hypertrophy that has not been previously reported in the English-language literature is transient cortical blindness. We describe such a case, which occurred in a 6-year-old boy who presented with a sudden loss of vision and subsequent unconsciousness. He had experienced hypercapnia and was resuscitated via endotracheal tube ventilation. Laboratory and radiologic assessments found no pathology except for extremely enlarged adenoid tissue. Once the patient was stabilized, an urgent adenotonsillectomy was performed. The patient recovered well, and his vision and respiratory symptoms resolved. Severe hypertrophy of the adenoid tissue can cause hypercapnia and acidosis secondary to upper airway obstruction. The possibility of adenoid hypertrophy and hypercapnia should be kept in mind in cases of transient cortical blindness. Aggressive treatment, including early intubation and adenoidectomy, may lead to a rapid resolution of symptoms.

To determine different clinical presentations of vitamin B12 deficiency in infants. Infants at the age of 1–20 mo admitted to infancy clinic of authors’ hospital between January 2011–2013 with various clinical presentations due to vitamin B12 deficiency were included in the study. Hospital records of all the patients were evaluated by means of history, physical, laboratory, imaging examinations and treatment. The diagnosis was based on a nutritional history of mothers and infants, clinical findings, hematological evaluation, and low level of serum vitamin B12. A total of 20 patients with a mean age of 6.65 ± 4.5 mo were included in the study. The weight and height were below the third percentile in four patients. The most common symptoms of the patients were; infections in 30 %, pallor in 25 %, hypotonia and neuro-developmental delay in 25 %, refusal to solid food or to suck in 20 %, failure to thrive in 15 %, fatigue in 10 %. Twenty-five percent of patients had neurologic signs and symptoms. Anemia was found in 16/20 (80 %) patients. Three (15 %) patients had leukopenia, 7 (35 %) had neutropenia, 2 (10 %) patients had thrombocytopenia. All of the mothers had vitamin B12 deficiency. All of the patients were fed with breast milk. Cyanocobalamin was administered to all the patients and mothers. After the treatment, clinical and laboratory findings of all the patients improved. Vitamin B12 deficiency should be considered in the differential diagnosis of some hematological, neurological, and gastrointestinal disturbances of infants.

A 2-year-old girl patient was admitted with intractable diarrhea, respiratory infections, and seizures. She was the first child of the first-degree parents. She was born at term with a birth weight of 2300 g. Physical examination revealed weight 6800 g, height 76 cm, and head circumference 41 cm, below the third percentile. Findings included sparse and dull hair, nail dystrophy, and proximally located thumbs (Figure). Aphthous lesions were observed on the oral mucosa. Neurologic examination disclosed poor head control. She could not sit without support and had hyper-reactive deep tendon reflexes.

Colchicine is frequently used in the treatment of familial Mediterranean fever (FMF). First symptoms of colchicine intoxication are gastrointestinal disturbances, such as abdominal cramps, diarrhea, pancytopenia and so on. Herein, we report a female FMF patient with pancytopenia and hemophagocytic lymphohitiocytosis (HLH), following colchicine intoxication for committing suicide. To our knowledge, this is the first reported case of a patient with HLH associated with colchicine intoxication.

Mowat-Wilson syndrome (MWS) is characterized by moderate to severe intellectual disability and distinctive facial features in association with variable structural congenital anomalies/clinical features including congenital heart disease, Hirschsprung disease, hypospadias, agenesis of the corpus callosum, short stature, epilepsy, and microcephaly. Less common clinical features include ocular anomalies, craniosynostosis, mild intellectual disability, and choanal atresia. These cases may be more difficult to diagnose. In this report, we add 28 MWS patients with molecular confirmation of ZEB2 mutation, including seven with an uncommon presenting feature. Among the "unusual" patients, two patients had clinical features of charge syndrome including choanal atresia, coloboma, cardiac defects, genitourinary anomaly (1/2), and severe intellectual disability; two patients had craniosynostosis; and three patients had mild intellectual disability. Sixteen patients have previously-unreported mutations in ZEB2. Genotype-phenotype correlations were suggested in those with mild intellectual disability (two had a novel missense mutation in ZEB2, one with novel splice site mutation). This report increases the number of reported patients with MWS with unusual features, and is the first report of MWS in children previously thought to have CHARGE syndrome. These patients highlight the importance of facial gestalt in the accurate identification of MWS when less common features are present.

Background In developing countries, nutritional vitamin B12 deficiency in infants because of maternal deficiency often causes hematological and neurological disorders. However, epilepsy is a rare manifestation of vitamin B12 deficiency. The biological basis for the observed neurological symptoms of infantile vitamin B12 deficiency remains uncertain. There are only a few reports in the English literature regarding the relationship between infantile spasms and vitamin B12 deficiency. Patients We report two unrelated infants having infantile spasms associated with vitamin B12 deficiency related to maternal nutritional deficiency. Results During the first month of adrenocorticotropic hormone (ACTH), phenobarbital, and vitamin B12 treatments, both infants' abnormalities resolved. After 3 months, electroencephaography was completely normal. ACTH and phenobarbital treatments were ended. The children are disease-free 9 months after the treatment. Conclusions We suggest that vitamin B12 deficiency should be considered in the differential diagnosis of infantile spasms as a treatable cause, especially with a history of maternal nutritional deficiency.