Syndromes predisposing to leukemia are a major cause of inherited cytopenias in children.

Prolonged cytopenias are a non-specific sign with a wide differential diagnosis. Among inherited disorders, cytopenias predisposing to leukemia require a timely and accurate diagnosis to ensure appropriate medical management, including adequate monitoring and stem cell transplantation prior to the development of leukemia. We aimed to define the types and prevalences of the genetic causes leading to persistent cytopenias in children.

Pediatric severe factor XI deficiency: A multicenter study.

Background: Factor XI (FXI) deficiency is a rare autosomal recessive bleeding disorder. Only scarce publications address its clinical features in children. The increased prevalence of FXI deficiency in Israel enabled data collection for this large multicenter cohort study.

Pediatric immune thrombocytopenia: apoptotic markers may help in predicting the disease course.

Background: In all, 15-30% of pediatric immune thrombocytopenia (ITP) patients will remain chronically thrombocytopenic at 1 year post diagnosis. All attempts to classify patients at diagnosis have proven unsuccessful. We hypothesized that a different pathophysiology is responsible for non-chronic versus chronic pediatric ITP.

Essential thrombocythemia A retrospective case series.

Background: Essential thrombocythemia (ET) is rare in children, and pediatric guidelines are lacking. Therefore, we aimed to evaluate ET diagnosis and treatment in a pediatric cohort.

Procedure: Data of patients with ET from three hospitals were reviewed.

Characterization and genotype-phenotype correlation of patients with Fanconi anemia in a multi-ethnic population.

Fanconi anemia (FA), an inherited bone marrow failure (BMF) syndrome, caused by mutations in DNA repair genes, is characterized by congenital anomalies, aplastic anemia, high risk of malignancies and extreme sensitivity to alkylating agents. We aimed to study the clinical presentation, molecular diagnosis and genotype-phenotype correlation among patients with FA from the Israeli inherited BMF registry. Overall, 111 patients of Arab (57%) and Jewish (43%) descent were followed for a median of 15 years (range: 0.

Thiopurine Therapy for Inflammatory Bowel Disease During Pregnancy Is Not Associated with Anemia in the Infant.

Introduction: Thiopurine exposure throughout pregnancy in patients with inflammatory bowel diseases (IBD) is common and teratogenically safe. Late consequences of in utero exposure to thiopurines and its metabolite, 6-thioguanine nucleotides (6-TGN), such as neonatal and infant anemia are still disputed.

Aim: To evaluate whether 6-TGN exposure during pregnancy influences anemia in infants at 1 year of life.

Targeted next generation sequencing for the diagnosis of patients with rare congenital anemias.

Background: Most patients with anemia are diagnosed through clinical phenotype and basic laboratory testing. Nonetheless, in cases of rare congenital anemias, some patients remain undiagnosed despite undergoing an exhaustive workup. Genetic testing is complicated by the large number of genes involved in rare anemias and the similarities in the clinical presentation of the different syndromes.

STAT3 gain-of-function mutations associated with autoimmune lymphoproliferative syndrome like disease deregulate lymphocyte apoptosis and can be targeted by BH3 mimetic compounds.

Autoimmune lymphoproliferative syndrome (ALPS) is typically caused by mutations in genes of the extrinsic FAS mediated apoptotic pathway, but for about 30% of ALPS-like patients the genetic diagnosis is lacking. We analyzed 30 children with ALPS-like disease of unknown cause and identified two dominant gain-of-function mutations of the Signal Transducer And Activator Of Transcription 3 (STAT3, p.R278H, p.

Quantification of specific T and B cells immunological markers in children with chronic and transient ITP.

Background: Immune thrombocytopenic purpura (ITP) is characterized by a transient (nonchronic) or permanent (chronic) decline in the number of platelets. Predicting the course of ITP, at the time of diagnosis, is of importance. Here we studied at diagnosis, clinical and immunological parameters in order to distinguish between different courses.

Quantitation of bleeding symptoms in a national registry of patients with inherited platelet disorders.

Background: Inherited platelet deficiency and/or dysfunction may be more common in the general population than has previously been appreciated. In 2013 the Israeli Inherited Platelet Disorder (IPD) Registry was established.

Methods: Clinical and laboratory data were collected to pre-specified registration forms.

Deregulation of Fas ligand expression as a novel cause of autoimmune lymphoproliferative syndrome-like disease.

Autoimmune lymphoproliferative syndrome is frequently caused by mutations in genes involved in the Fas death receptor pathway, but for 20-30% of patients the genetic defect is unknown. We observed that treatment of healthy T cells with interleukin-12 induces upregulation of Fas ligand and Fas ligand-dependent apoptosis. Consistently, interleukin-12 could not induce apoptosis in Fas ligand-deficient T cells from patients with autoimmune lymphoproliferative syndrome.

Genetic analysis and clinical picture of severe congenital neutropenia in Israel.

Background: The relative frequency of mutated genes among patients with severe congenital neutropenia (SCN) may differ between various ethnic groups. To date, few population-based genetic studies have been reported. This study describes the genetic analysis of 32 Israeli patients with SCN.

Asthma and hemoglobinopathy: when is supplemental oxygen required?

Asthma is the most common reason for referral to the emergency department in childhood. In severe attacks, supplemental O2 is given when oxygen saturation level is <90%. Described herein is the case of a child with persistent low oxygen saturation as measured on pulse oximetry (S(p)O2) after full clinical recovery from an asthma attack.

Neurologic manifestations of Fusobacterium infections in children.

Unlabelled: Fusobacterium necrophorum causes various clinical syndromes, ranging from otitis media to life-threatening Lemierre's syndrome. The purpose of this study was to review our experience with pediatric Fusobacterium infections. The medical records of all children aged 0 to 18 years who were diagnosed between 1999 and 2011 with Fusobacterium infection were reviewed.

Mycoplasma pneumonia Infection: A Possible Trigger for Immune Thrombocytopenia.

Mycoplasma pneumonia (M. pneumonia) is usually not considered among the several pathogens that induce immune thrombocytopenia (ITP). We report a child with a clinical diagnosis of severe ITP that was associated with M.

Preimplantation genetic diagnosis for fetal neonatal alloimmune thrombocytopenia due to antihuman platelet antigen maternal antibodies.

Objective: To develop a reliable preimplantation genetic diagnosis protocol for antihuman platelet antigen-1 incompatibility for a family in whom antenatal treatment was not possible because of the mother's hypersensitivity to intravenous immunoglobulin (IVIG).

Methods: Haplotypes were constructed from genomic DNA of the family members. A polymerase chain reaction protocol that included eight microsatellite polymorphic markers and the ITGB3-specific (T196C, rs5918) polymorphism were multiplexed to be used in a single cell protocol, and single blastomeres were analyzed.

[Vibrio vulnificus infection outside of the fish ponds in northern Israel: acquisition in the "Einot Tzukim" springs near the Dead Sea].

Vibrio vulnificus is a Gram-negative bacterium that may cause severe skin and systemic infection after exposure of open wounds to contaminated water, especially in patients with underlying disease such as immune-deficiency, iron overload or end stage liver or renal disease. The V. vulnificus infection has been reported in Israel almost exclusively after exposure to Tilapia fish cultivated in fresh water fish ponds in northern Israel.

Burkitt lymphoma in children: the Israeli experience.

Background: We analyzed the results of the French-American-British-LMB 96 protocol performed in 9 centers in Israel on 88 patients with B-cell non-Hodgkin lymphoma treated from 2000 to 2005.

Procedure: The majority of the patients was male (63/88, 72%), with a median age of 8.9 years (range, 2.

Respiratory failure and hypercoagulability in a toddler with Lemierre's syndrome.

A 3.5-year-old healthy boy with 4 days of fever was referred to the emergency department for respiratory distress. The physical examination was remarkable for stupor, tachycardia, tachypnea, and dyspnea.

Serum ferritin level as a predictor of impaired growth and puberty in thalassemia major patients.

Objective: Previous studies suggested that in patients with thalassemia major, initiating deferoxamine (DFO) therapy before puberty can prevent iron-induced failure of growth and puberty. However, early initiation of chelation has also been associated with DFO toxicity. The aim of this retrospective study was to determine the prevalence rates of endocrine complications and DFO bone toxicity in our thalassemia major patients and to correlate them with the degree of iron chelation.

High incidence of early cholelithiasis detected by ultrasonography in children and young adults with hereditary spherocytosis.

Objectives: Retrospective cholecystography studies in adults with hereditary spherocytosis (HS) suggested detectable gallstones in 37% to 43% of patients. Since longitudinal studies using biliary ultrasonography are unavailable, the aim of the present study was to determine the incidence of gallstone disease, as detected by biliary ultrasonography, in children and young adults with HS. As individuals with HS who co-inherit Gilbert syndrome have a greater risk of developing gallstones, uridine diphosphate-glucuronyl transferase (UGT-1A) gene polymorphism was also determined.

Isolated extrarenal papillary carcinoma in a child.

A previously healthy 12-year-old boy presented with a mass in the right retroperitoneum adjacent to an ipsilateral hypoplastic kidney. Complete resection of the tumor and kidney were done. The tumor was found to be papillary adenocarcinoma lying 3 cm apart from a contracted kidney, which was free of tumor.