Hannah Tamary

Biotecnologie Avanzate, Napoli, Campania, Italy

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Publications (105)349.02 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The molecular basis of α-thalassemia (α-thal) is complex. The use of multiplex ligation-dependent probe amplification (MLPA) has offered the possibility of identifying more gene deletions causing α-thal. Our objective was to determine the molecular basis of two patients with Hb H (β4) disease. By using MLPA in combination with comparative genomic hybridization (CGH) we identified two novel α-globin gene cluster deletions: a 30 kb deletion (patient 1) we refer to as – –JAL and a large 216 kb deletion (patient 2) we refer to as – –LOD. Patient 1 was a compound heterozygote for – –JAL and –α3.7 (rightward deletion). Twelve family members of patient 1 carrying the – –JAL deletion were available for evaluation: five with – –JAL/–α3.7, four with – –JAL/αHph Iα and three with – –JAL/αα. Their clinical picture of compound heterozygosity was compatible with moderate Hb H disease. In patient 2 (– –LOD/–α3.7), no additional symptoms were present despite the heterozygous deletion of seven known genes, three non coding RNAs (ncRNAs), four unknown genes and two pseudo genes. Further analysis of more patients with α-thal deletions will have implications for genetic counseling and appropriate therapy.
    Hemoglobin 09/2014; · 0.89 Impact Factor
  • Joanne Yacobovich, Hannah Tamary
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    ABSTRACT: The increased longevity of patients with thalassemia and sickle cell disease (SCD) introduces new clinical challenges due to the accumulation of disease-related morbidity, psychosocial issues and health care adjustments. Patients with thalassemia major now live into adulthood without suffering heart failure but must confront delayed puberty, impaired fertility and progressive bone disease. The increased survival in SCD brings to the front previously unrecognized complications including pulmonary hypertension, silent cerebral infarcts and also reproductive dysfunction. Adolescents and young adults (AYAs) have age-related psychosocial needs in their transition from the pediatric health care environment to the adult system. In this review we present the uniquely age-related medical issues facing the AYA thalassemia and SCD cohort in their transition into adulthood. © 2014 S. Karger AG, Basel.
    Acta haematologica. 01/2014; 132(3-4):340-7.
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    ABSTRACT: Hemophagocytic lymphohistiocytosis (HLH) is caused by an excessive activation of nonmalignant macrophages. Renal lesions have been described in association with, but always after, HLH diagnosis. We describe a previously healthy 26-month-old girl who presented originally with steroid-responsive nephrotic syndrome (NS), but after 4 months, on the first NS relapse, experienced numerous complications (many of them reported to accompany NS as single events). Clinical and laboratory signs of HLH evolved with time and led to deterioration of her condition and death, within 5 months of her original presentation. To our knowledge, this is the first report of NS antedating the presentation of HLH.
    Pediatric Nephrology 08/2013; · 2.94 Impact Factor
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    ABSTRACT: The congenital dyserythropoietic anemias (CDAs) are hereditary disorders characterized by distinct morphological abnormalities of marrow erythroblasts. The unveiling of the genes mutated in the major CDA subgroups (I-CDAN1, II-SEC23B) has now been completed with the recent identification of the CDA III gene (KIF23). KIF23 encodes mitotic kinesin-like protein 1 which plays a critical role in cytokinesis, while the cellular role of the proteins encoded by CDAN1 and SEC23B is still unknown. CDA variants with mutations in erythroid transcription factors genes (KLF1, GATA-1) have been recently identified. Molecular diagnosis of CDA is now possible in most patients.
    Blood 08/2013; · 9.78 Impact Factor
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    ABSTRACT: To evaluate the predictive value of clinical features at diagnosis of immune thrombocytopenia (ITP) for resolution of disease. Hospital records of 472 consecutive children (<18 years old) with ITP cared for at 2 participating centers were reviewed retrospectively and data related to the initial presentation were recorded. Logistic regression analysis was used for calculating prediction of resolution at 3, 6, and 12 months from diagnosis. The most significant predictors for resolution of ITP at 3, 6, and 12 months were age at onset <10 years and abrupt onset (history of <2 weeks of bleeding). We designed a prediction rule for ITP chronicity based on these criteria. The rate of developing chronic ITP for low, intermediate, and high risk children at diagnosis of ITP was 11%, 39%, and 63%, respectively. Recovery rate at 3 months for low, intermediate, and high risk children was 72%, 43% and 30%, respectively. We present a simple rule to predict recovery from ITP at 3, 6, and 12 months from diagnosis. For prediction of resolution at 3 months, our rule was in agreement with the more complex, previously described Nordic score. Prediction of resolution of ITP may enable practitioners to better inform children and parents at the time of diagnosis, resulting in reduced anxiety and improved quality of life.
    The Journal of pediatrics 07/2013; · 4.02 Impact Factor
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    ABSTRACT: We describe the clinical and laboratory features of a family of Arab ancestry and consanguinity. Five affected individuals were diagnosed in two sibships. All affected members have small platelets, severe to moderate thrombocytopenia of neonatal onset, increased bleeding tendency and bleeding complications such as: life-threatening massive hemoperitoneum due to corpus luteum rupture during ovulation and severe mucosal bleeding. The familial involvement and early onset of the disease support the presence of a congenital genetic disorder with an autosomal recessive inheritance pattern. This does not fit the clinical spectrum of any of the currently known thrombocytopenia disorders. Pediatr Blood Cancer 2013;9999:XX-XX. © 2013 Wiley Periodicals, Inc.
    Pediatric Blood & Cancer 05/2013; · 2.35 Impact Factor
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    ABSTRACT: Thrombocytosis is a common finding and is a frequent cause of referral for further investigation. The MPL Baltimore (Lys39Asn) mutation has been reported as a cause of thrombocytosis in 7% of African Americans. We describe an 11-month-old Ethiopian Jewish boy referred for evaluation of thrombocytosis who was found to be homozygous for MPL Baltimore. So far, there is no indication whether patients with thrombocytosis who have this mutation, particularly homozygotes, are at increased risk of thrombotic or hemorrhagic complications. Nevertheless, this entity should be considered in the differential diagnosis of every patient with thrombocytosis, particularly those of African origin.
    Journal of Pediatric Hematology/Oncology 04/2013; 35(3):e112-4. · 0.97 Impact Factor
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    ABSTRACT: Although the majority of children with immune thrombocytopenia (ITP) have a short duration of the disease, the very rare but significant complications of the disease often cause fear and anxiety among families of children with ITP. Added to the reduced quality of life (QoL) of those children are restrictions imposed on daily activities to avoid trauma. Treatment decisions in chronic ITP and especially regarding splenectomy are hampered by the inability to predict when recovery will take place. Identification of predictors of recovery would be beneficial for improving treatment decisions and QoL of both children and families. This literature review focuses on clinical parameters and emerging genetic biomarkers for prediction of duration of childhood ITP. Higher recovery rates were found among infants with newly diagnosed ITP. In contrast onset of the disease at adolescence was associated with worse recovery rates. Six clinical features were found to be associated with short duration of disease; the most prominent ones were abrupt onset of bleeding symptoms (<2 weeks) and age at onset≤10 years. Two genetic biomarkers have been suggested as predictors of chronic disease: overexpression of vanin-1 (VNN-1), an oxidative stress sensor, and the Q63R missense variant of the gene encoding the cannabinoid receptor type 2. To be clinically useful each of those predictors requires further validation in larger studies. Genetic biomarkers will potentially offer direct and early prognosis estimation.
    Seminars in Hematology 01/2013; 50 Suppl 1:S71-4. · 3.36 Impact Factor
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    ABSTRACT: : We constructed an animal model to examine the possibility that erythrophagocytosis may contribute to decreased hemoglobin (Hgb) levels in acute infection in mice. : BALB/c mice weighing 20 to 25 g were injected (intraperitoneally) with lipopolysaccharide (LPS) (Escherichia coli serotype) of some concentrations. Control mice were injected intraperitoneally with saline (0.5 mL). Two and 4 hours after LPS administration, mice were bled (0.25 mL) for complete blood count measures and tumor necrosis factor-α and interleukin-6 levels. The mice were then killed, and their spleen, liver, and bone marrow were examined microscopically for erythrophagocytosis. : After LPS administration, mouse Hgb and hematocrit levels dropped significantly. At 4 hours after LPS injection, all Hgb and hematocrit concentrations were found to be significantly lower compared with that of controls (P=0.002 and 0.001, respectively). Significantly increased concentrations of tumor necrosis factor-α and interleukin-6 were evident after LPS injection. Prominent hepatic erythrophagocytosis was observed in the LPS-injected mice compared with controls. A significant across-group difference was observed at 4 hours, driven by significantly higher values in group 500 mcg versus controls (P=0.005) and 100 mcg (P=0.025). A significant increase in erythrophagocytes was observed at 2 to 4 hours in the 500 mcg LPS group (P=0.044). : Erythrophagocytosis may play a role in anemia associated with acute infection in mice.
    Journal of Pediatric Hematology/Oncology 01/2013; 35(1):14-7. · 0.97 Impact Factor
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    ABSTRACT: OBJECTIVE: The epsilon gamma delta beta (εγδβ) thalassemias are rare sporadic disorders caused by deletion of the β-globin gene cluster. The main clinical feature is marked prenatal and neonatal anemia that resolves spontaneously within a few months. Reports originating mainly from Europe have so far identified 30 such deletions The aim of the present work was to describe a novel 1.78Mb deletion, the longest ever reported, and to detail the clinical features in 12 members of an extended Bedouin family. METHODS: The deletion was identified by globin gene multiplex ligation-dependent probe amplification (MLPA) of the β-globin cluster and further characterized by comparative genomic hybridization. Past and present clinical and laboratory data of 10 symptomatic and 2 asymptomatic patients were collected. RESULTS: A 1.78 Mb εγδβ deletions the largest ever described was identified in all patients. Although other genes were included in the deletion, no other symptoms were observed. Of the 10 symptomatic fetuses and neonates, 3 died of the disease. The remainder required packed cell transfusions during the first months of life. Pregnancy complications included intrauterine growth restriction and oligohydramnios, as well as, additional neonatal complications including prematurity and persistent pulmonary hypertension of the neonate CONCLUSIONS: We suggest that εγδβ thalassemia be added to the list of hemoglobinopathies that can cause neonatal anemia and that MLPA of the β-globin cluster be used to confirm its diagnosis. Careful surveillance during pregnancy is important to reduce neonatal mortality and morbidity, especially given the dramatic improvement that occurs later. © 2012 John Wiley & Sons A/S.
    European Journal Of Haematology 12/2012; · 2.55 Impact Factor
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    ABSTRACT: OBJECTIVE: Congenital dyserythropoietic anemia (CDA) is a rare group of red blood cell disorders with ineffective erythropoiesis and secondary hemochromatosis. Inappropriate suppression of hepcidin and high levels of growth differentiation factor 15 (GDF15) have been described in CDA I and II patients, probably contributing to secondary hemochromatosis. Hemojuvelin (HJV) is an important regulator of serum hepcidin while soluble form of HJV (s-HJV) competitively down-regulates hepcidin. METHODS: We determined the soluble hemojuvelin (s-HJV) levels in 17 patients with CDA I and in 17 healthy volunteers (HV) and looked for correlations with other parameters of iron overload and erythropoiesis. RESULTS: Significantly higher levels of s-HJV were found in patients (2.32±1.40 mg/L) compared to healthy volunteers (0. 69±0.44 mg/L) (p= 0.001). Western blot analysis confirmed the presence of high levels of s-HJV in CDA I patients. s-HJV positively correlated with serum ferritin, erythropoietin, soluble transferrin receptor, GDF-15, and negatively correlated with hepcidin to ferritin ratios. CONCLUSIONS: We for the first time documented high levels of serum s-HJV in CDA I patients suggesting that it may contribute to iron loading pathology in CDA I and eventually in other anemias with ineffective erythropoiesis. © 2012 John Wiley & Sons A/S.
    European Journal Of Haematology 10/2012; · 2.55 Impact Factor
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    ABSTRACT: Neutral lipid storage disease (Chanarin-Dorfman syndrome) is a rare autosomal recessive disorder of lipid metabolism, characterized by systemic accumulation of neutral lipids in multiple tissues. We report a case of a 14-year-old girl with generalized ichthyosis, liver cirrhosis, and a hearing impairment. A peripheral blood smear demonstrated marked cytoplasmatic vacuoles in most polymorphonuclear cells (Jordan's anomaly). Bone marrow examination revealed vacuoles in myeloid precursors. Genetic analysis showed that the patient was homozygous for the p.Arg312Ter mutation in the CGI-58 gene, a key enzyme in lipid metabolism. The peripheral blood smear is diagnostic, and should be performed in any patient with ichthyosis.
    Journal of Pediatric Hematology/Oncology 10/2012; · 0.97 Impact Factor
  • Shraga Aviner, Ehud Even-Or, Hannah Tamary
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    ABSTRACT: Essential thrombocytosis (ET) is rare in children, sometimes difficult to be distinguished from secondary thrombocytosis. This report concerns 2 children with extreme thrombocytosis of 4100 × 10(9)/L and 1644 × 10(9)/L with partial and complete remission at 3 months and 4 years from diagnosis, with a follow-up of 4 and 17 years, respectively, with no cytoreduction therapy. Diagnosis of ET was suggested according to accepted criteria. However, spontaneous remission of the thrombocytosis argues for the diagnosis of secondary thrombocytosis. These patients highlight the complexity of distinguishing childhood ET from secondary thrombocytosis and the need for cautious personalized decision on cytoreduction therapy.
    Pediatric Hematology and Oncology 05/2012; 29(4):372-7. · 0.90 Impact Factor
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    ABSTRACT: The diagnosis, treatment, and prognosis of immune trombocytopenic purpura (ITP) have been extensively studied, but data on its effect on health-related quality of life in children remain sparse. To shed more light on this issue, we administered the Kids' ITP Tools (KIT) questionnaire to 17 children with ITP attending a tertiary pediatric medical center and their parents (n=34). The mean KIT score was significantly lower in the parents' group than in the children's group (P=0.000). The main domains of concern for the parents were disease side effects and their child's future; the children were mostly concerned about the need to restrict physical activities. The presence of acute versus chronic disease had no impact on the KIT score in either group. These findings stress the need to develop different interventional programs for children with ITP and their parents to provide appropriate support to each.
    Journal of Pediatric Hematology/Oncology 01/2012; 34(1):2-5. · 0.97 Impact Factor
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    ABSTRACT: Congenital Dyserythropoietic Anemia type II is an autosomal recessive disorder characterized by unique abnormalities in the differentiation of cells of the erythroid lineage. The vast majority of CDA II cases result from mutations in the SEC23B gene. To date, 53 different causative mutations have been reported in 86 unrelated cases (from the CDA II European Registry), 47 of them Italian. We have now identified SEC23B mutations in 23 additional patients, 17 Italians and 6 non-Italian Europeans. The relative allelic frequency of the mutations was then reassessed in a total of 64 Italian and 45 non-Italian unrelated patients. Two mutations, E109K and R14W, account for over one-half of the cases of CDA II in Italy. Whereas the relative frequency of E109K is similar in Italy and in the rest of Europe (and is also prevalent in Moroccan Jews), the relative frequency of R14W is significantly higher in Italy (26.3% vs. 10.7%). By haplotype analysis we demonstrated that both are founder mutations in the Italian population. By using the DMLE+ program our estimate for the age of the E109K mutation in Italian population is ≈2,200 years; whereas for the R14W mutation it is ≈3,000 years. We hypothesize that E109K may have originated in the Middle East and may have spread in the heyday of the Roman Empire. Instead, R14W may have originated in Southern Italy. The relatively high frequency of the R14W mutation may account for the known increased prevalence of CDA II in Italy.
    American Journal of Hematology 09/2011; 86(9):727-32. · 4.00 Impact Factor
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    ABSTRACT: Primary immune thrombocytopenia is a bleeding diathesis with an unknown etiology in predisposed individuals with immune disturbances. Although it is claimed that children and adults differ in clinical and laboratory aspects, few data exist to corroborate this observation. Our objective was to assess comparative data from children and adults with newly diagnosed immune thrombocytopenia. Clinical and laboratory data of 1,784 children and 340 adults were extracted from the Pediatric and Adult Registry on Chronic Immune Thrombocytopenia. The registry represents a prospective cohort of children and adults with newly diagnosed immune thrombocytopenia. Participating investigators registered their patients immediately after the diagnosis using a web based data transfer. Children aged under 16 years were compared with adults aged 16 years and over with descriptive statistical analyses. The presenting mean platelet count of children and adults was 18.1 and 25.4 × 10(9)/L. Signs of bleeding were reported in 24% of children and in 23% of adults, and intracranial hemorrhage in 10 of 1,784 children and in 6 of 340 adults. Co-morbidity was observed in 3.9% of children and in 30% of adults. Bone marrow aspiration and laboratory tests (antinuclear antibodies, human immunodeficiency and hepatitis C virus) were performed more frequently in adults. Children and adults were followed with a 'watch and wait' strategy in 20% and in 29%, respectively. Immunoglobulins were used more frequently in children and corticosteroids in adults. Comparative data of children and adults with newly diagnosed immune thrombocytopenia revealed similarities in presenting platelet counts and in bleeding, whereas differences occurred in co-morbidity, diagnostic procedures and therapy.
    Haematologica 08/2011; 96(12):1831-7. · 5.94 Impact Factor
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    ABSTRACT: For many recessive genetic syndromes, carrier frequencies have been assessed through screening studies in founder populations but remain unclear in heterogeneous populations. One such syndrome is Fanconi Anemia (FA). FA is a model disease in cancer research, yet there are no contemporary data on carrier frequency or prevalence in the general United States (US) population or elsewhere. We inferred carrier frequency from birth incidence using the Hardy-Weinberg law. We estimated prevalence using birth incidence and survival data. We defined "plausible ranges" to incorporate uncertainty about completeness of case ascertainment. We made estimates for the US and Israel using demographic data from the Fanconi Anemia Research Fund and Israeli Fanconi Anemia Registry. In the US, a plausible range for the carrier frequency is 1:156-1:209 [midpoint 1:181]; we estimate that 550-975 persons were living with FA in 2010. For Israel, a plausible range for the carrier frequency is 1:66-1:128 [midpoint 1:93] in line with founder screening studies; we estimate that 40-135 Israelis were living with FA in 2008. The estimated US FA carrier frequency of 1:181 is significantly higher than the historical estimate of 1:300; hence, the gap may be narrower than previously recognized between the US carrier frequency and higher carrier frequencies of around 1:100 in several founder groups including Ashkenazi Jews. Assessment of cancer risks in heterozygous carriers merits further study. Clinical trials in FA will require co-ordination and innovative design because the number of living US patients is probably less than 1,000.
    American Journal of Medical Genetics Part A 08/2011; 155A(8):1877-83. · 2.30 Impact Factor
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    ABSTRACT: The course of hereditary spherocytosis (HS) may be subject to hemolytic episodes, sometimes requiring blood transfusion. The aim of this study was to evaluate the efficacy of a short course of steroid therapy in elevating hemoglobin levels during hemolytic crisis. The files of all patients followed for HS from 1968 to 2009 at our hospital were reviewed. Outcome of hemolytic crises was compared between steroid-treated and untreated patients; patients given packed red blood cell transfusion(s) or erythropoietin treatment were excluded. A good outcome was defined as an increase of at least 20% in hemoglobin level from the nadir within 1 week. Of the 118 patients with HS who attended our hospital during the study period, 20 were treated with steroids and 9 received no treatment. Mean nadir hemoglobin level in both groups was 6.9 g/dl. The study group had a total of 50 steroid-treated hemolytic crises of which 37 (74%) responded favorably to treatment. Treatment failure was significantly associated with a low dose (<1 mg/kg/day) or short duration (<1 week) of treatment. The nine untreated patients had 16 hemolytic crises, of which 25% had a good outcome. Steroid therapy was significantly more effective than no therapy in increasing hemoglobin level (P = 0.015) in these hemolytic crises. Steroid therapy may be effective in augmenting hemoglobin levels during hemolytic crises in patients with moderate HS and eventually will result in a reduced need for RBC transfusion.
    Pediatric Blood & Cancer 08/2011; 57(2):303-5. · 2.35 Impact Factor
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    ABSTRACT: Acknowledgments: we thank all patients who continue to partici-pate in the PARC-ITP Registry and the staff of the participating institutions. We are indebted to Verena Stahel, Caroline Asal Martin and Monika Imbach for data administration and secretar-ial work. We thank all investiga-tors of the PARC-ITP Registry who support ICIS and generously pro-vided us with their patient data.
    Hematologica. 07/2011; 22.
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    ABSTRACT: Thrombotic thrombocytopenic purpura is caused by an imbalance of von Willebrand factor and its cleaving protease, which leads to the formation of microthrombi in end-organs. It rarely occurs in the pediatric population. Plasma exchange can significantly reduce mortality and morbidity. We present a 14-month-old infant in whom clinical and laboratory abnormalities compatible with thrombotic thrombocytopenic purpura were noted several days after resection of a large pelvic tumor. Treatment with double volume plasma exchange on postoperative day 5 led to complete resolution of the renal failure, thrombocytopenia, anemia, and neurological manifestations. ADAMTS13 inhibitors were negative and no mutations were found in factor H, factor I, membrane cofactor protein, and thrombomodulin to account for genetic predisposition to thrombotic thrombocytopenic purpura or atypical hemolytic uremic syndrome. Postoperative anemia, thrombocytopenia, fever, and neurological deficits in children should raise the suspicion of thrombotic thrombocytopenic purpura. Early diagnosis is important because the disorder is readily and efficiently treated with plasma exchange.
    Journal of Pediatric Surgery 04/2011; 46(4):764-6. · 1.38 Impact Factor

Publication Stats

2k Citations
349.02 Total Impact Points

Institutions

  • 2013
    • Biotecnologie Avanzate
      Napoli, Campania, Italy
    • Hebrew University of Jerusalem
      Yerushalayim, Jerusalem District, Israel
  • 2004–2013
    • Tel Aviv University
      • Department of Pediatrics
      Tell Afif, Tel Aviv, Israel
  • 2012
    • Barzilai Medical Center Ashkelon
      Majdal, Southern District, Israel
  • 2001–2012
    • Ben-Gurion University of the Negev
      • Division of Pediatrics
      Be'er Sheva`, Southern District, Israel
  • 2000–2012
    • Soroka Medical Center
      • Division of Pediatrics
      Be'er Sheva`, Southern District, Israel
    • Rabin Medical Center
      Tell Afif, Tel Aviv, Israel
  • 1994–2012
    • Schneider Children's Medical Center of Israel
      Petah Tikva, Central District, Israel
    • The Children's Hospital of Philadelphia
      • Division of Hematology
      Philadelphia, Pennsylvania, United States
  • 2011
    • Edith Wolfson Medical Center, Holon
      Yerushalayim, Jerusalem District, Israel
    • National Institutes of Health
      • Division of Cancer Epidemiology and Genetics
      Bethesda, MD, United States
  • 2008
    • CLALIT
      Tell Afif, Tel Aviv, Israel
  • 2003–2007
    • Hôpital Bicêtre (Hôpitaux Universitaires Paris-Sud)
      Lutetia Parisorum, Île-de-France, France