Secondary thrombocytosis is a frequent secondary finding in childhood infection and inflammation.... more Secondary thrombocytosis is a frequent secondary finding in childhood infection and inflammation. Primary hereditary thrombocytosis may be caused by germline mutations within the genes encoding key regulators of thrombopoiesis, i.e., thrombopoietin (THPO) and its receptor c-MPL (MPL) or the receptor’s effector kinase Januskinase2 (JAK2). Furthermore, somatic mutations in JAK2, MPL, and in the gene-encoding calreticulin (CALR) have been described to act as driver mutations within the so-called Philadelphia-negative myeloproliferative neoplasms (MPNs), namely essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF). Increasing knowledge on the molecular mechanisms and on the clinical complications of these diseases is reflected by the WHO diagnostic criteria and European LeukemiaNet (ELN) recommendations on the management of adult MPN. However, data on childhood thrombocytosis are rare, and no consensus guidelines for pediatric thrombocytosis exist. Curr...
ZusammenfassungDie Sichelzellkrankheit ist global gesehen eine der häufigsten Erbkrankheiten über... more ZusammenfassungDie Sichelzellkrankheit ist global gesehen eine der häufigsten Erbkrankheiten überhaupt. Betroffen sind überwiegend Menschen aus dem subsaharischen West- und Zentralafrika; aber auch in bestimmten Mittelmeeranrainerstaaten, im Nahen Osten und in Teilen Indiens leben viele Erkrankte. Durch Migration nehmen die Patientenzahlen auch in Mittel- und Nordeuropa kontinuierlich zu. Die Sichelzellkrankheit ist eine extrem komplexe Erkrankung. Für die meisten Komplikationen stehen nur symptomatische Therapien zur Verfügung. Die einzige kurative, aber nur sehr zurückhal-tend angewendete Behandlungsoption ist die Stammzelltransplantation.Dieser Artikel fasst die wichtigsten Informationen über die Sichelzellkrankheit zusammen, die der niedergelassene Kinderarzt für seinen Praxisalltag benötigt.
ZusammenfassungDie Option der Behandlung von Kindern mit einer Eisenmangelanämie mit dem Eisen(II... more ZusammenfassungDie Option der Behandlung von Kindern mit einer Eisenmangelanämie mit dem Eisen(III)-hydroxid-Polymaltose-Komplex (EPK) wird in aktuellen Übersichtsartikeln und Leitlinien kaum berücksichtigt. Ziel: Basierend auf Behandlungsdaten aus einer hämatologischen Ambulanz soll die Wirksamkeit des EPK bei der Therapie der Eisenmangelanämie mit aktuellen Ergebnissen unterstrichen werden. Patienten, Methode: Es erfolgte eine retrospektive Analyse von 57 Patienten (Alter: 5–185 Monaten) mit der Diagnose Eisenmangelanämie, die mit EPK behandelt wurden. Ergebnisse: Die EPK-Therapie führte zu signifikanten Veränderungen von Hämoglobin, Hämatokrit, MCV, Serumferritin und löslichem Transferrinrezeptor (sTFR) sowie des sTFR-Index. Bis auf zwei Fälle von Obstipation traten keine unerwünschten Arzneimittelwirkungen auf. Schlussfolgerung: Die Therapie der Eisenmangelanämie mit EPK ist im Alltag der pädiatrischen Praxis erfolgreich und gut verträglich. Sie bietet eine effektive therapeutis...
Introduction: Hepatic siderosis, a result of chronic transfusion therapy, leads to hepatocellular... more Introduction: Hepatic siderosis, a result of chronic transfusion therapy, leads to hepatocellular injury and progression to chronic liver disease. Increases in serum transaminase levels are indicative of progressive liver damage. The effect of deferasirox (Exjade®, ICL670), a novel, once-daily oral chelator, on liver iron content and pathology in chronically transfused patients has been assessed in Phase II and III clinical studies. A sub-analysis of pooled data from the planned 4-year extension of two pivotal studies sought to correlate the long-term changes in serum ALT levels with those of serum ferritin in iron-overloaded patients during treatment with deferasirox. Methods: In these two clinical studies, 480 patients with β-thalassemia (β-thal), myelodysplastic syndromes (MDS), Diamond-Blackfan anemia (DBA), and other transfusion-dependent anemias received deferasirox at 5, 10, 20 or 30 mg/kg/day according to baseline liver iron concentrations for 12 months. In the extension pha...
Erythrocytosis is a rare disorder characterized by increased red cell mass and elevated hemoglobi... more Erythrocytosis is a rare disorder characterized by increased red cell mass and elevated hemoglobin concentration and hematocrit. Several genetic variants have been identified as causes for erythrocytosis in genes belonging to different pathways including oxygen sensing, erythropoiesis and oxygen transport. However, despite clinical investigation and screening for these mutations, the cause of disease cannot be found in a considerable number of patients, who are classified as having idiopathic erythrocytosis. In this study, we developed a targeted next generation sequencing panel encompassing the exonic regions of 21 genes from relevant pathways (~79Kb) and sequenced 125 patients with idiopathic erythrocytosis. The panel effectively screened 97% of coding regions of these genes, with an average coverage of 450X. It identified 51 different rare variants, all leading to alteration of protein sequence, with 57 out of 125 cases (45.6%) having at least 1 of these variants. Ten of these we...
Concurrent emergence of nephroblastoma (Wilms Tumor; WT) and neuroblastoma (NB) is rare and mostl... more Concurrent emergence of nephroblastoma (Wilms Tumor; WT) and neuroblastoma (NB) is rare and mostly observed in patients with severe subtypes of Fanconi anemia (FA) with or without VACTER-L association (VL). We investigated the hypothesis that early consequences of genomic instability result in shared regions with copy number variation in different precursor cells that originate distinct embryonal tumors. We observed a newborn girl with FA and VL (aplasia of the thumbs, cloacal atresia (urogenital sinus), tethered cord at L3/L4, muscular ventricular septum defect, and horseshoe-kidney with a single ureter) who simultaneously acquired an epithelial-type WT in the left portion of the kidney and a poorly differentiated adrenal NB in infancy. A novel homozygous germline frameshift mutation in PALB2 (c.1676_c1677delAAinsG) leading to protein truncation (pGln526ArgfsX1) inherited from consanguineous parents formed the genetic basis of FA-N. Spontaneous and induced chromosomal instability w...
At present, about 300 patients with thalassemia major are living in Germany. Starting in 1991, a ... more At present, about 300 patients with thalassemia major are living in Germany. Starting in 1991, a multicenter study in Germany has concentrated on identifying all patients suffering from thalassemia as well as on establishing a uniform therapy protocol including follow-up diagnostic procedures. After six years of study, the data of 198 patients suffering from thalassaemia major were analysed. The majority of these patients originate from endemic regions around the Mediterranean Sea. The patient's median age is 13.8 years (range 1-37.5 yrs.). At present, about 20% of patients are older than 21 years. Regarding transfusion therapy, a shortening of the average transfusion interval to 3 weeks in most cases occurred. Throughout the entire period, median baseline haemoglobin concentrations of 10.0 g/dl could be observed. The evaluation of serum ferritin levels revealed considerable differences depending on patients age. 60% of patients in the first decade of life showed good therapeuti...
Secondary thrombocytosis is a frequent secondary finding in childhood infection and inflammation.... more Secondary thrombocytosis is a frequent secondary finding in childhood infection and inflammation. Primary hereditary thrombocytosis may be caused by germline mutations within the genes encoding key regulators of thrombopoiesis, i.e., thrombopoietin (THPO) and its receptor c-MPL (MPL) or the receptor’s effector kinase Januskinase2 (JAK2). Furthermore, somatic mutations in JAK2, MPL, and in the gene-encoding calreticulin (CALR) have been described to act as driver mutations within the so-called Philadelphia-negative myeloproliferative neoplasms (MPNs), namely essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF). Increasing knowledge on the molecular mechanisms and on the clinical complications of these diseases is reflected by the WHO diagnostic criteria and European LeukemiaNet (ELN) recommendations on the management of adult MPN. However, data on childhood thrombocytosis are rare, and no consensus guidelines for pediatric thrombocytosis exist. Curr...
ZusammenfassungDie Sichelzellkrankheit ist global gesehen eine der häufigsten Erbkrankheiten über... more ZusammenfassungDie Sichelzellkrankheit ist global gesehen eine der häufigsten Erbkrankheiten überhaupt. Betroffen sind überwiegend Menschen aus dem subsaharischen West- und Zentralafrika; aber auch in bestimmten Mittelmeeranrainerstaaten, im Nahen Osten und in Teilen Indiens leben viele Erkrankte. Durch Migration nehmen die Patientenzahlen auch in Mittel- und Nordeuropa kontinuierlich zu. Die Sichelzellkrankheit ist eine extrem komplexe Erkrankung. Für die meisten Komplikationen stehen nur symptomatische Therapien zur Verfügung. Die einzige kurative, aber nur sehr zurückhal-tend angewendete Behandlungsoption ist die Stammzelltransplantation.Dieser Artikel fasst die wichtigsten Informationen über die Sichelzellkrankheit zusammen, die der niedergelassene Kinderarzt für seinen Praxisalltag benötigt.
ZusammenfassungDie Option der Behandlung von Kindern mit einer Eisenmangelanämie mit dem Eisen(II... more ZusammenfassungDie Option der Behandlung von Kindern mit einer Eisenmangelanämie mit dem Eisen(III)-hydroxid-Polymaltose-Komplex (EPK) wird in aktuellen Übersichtsartikeln und Leitlinien kaum berücksichtigt. Ziel: Basierend auf Behandlungsdaten aus einer hämatologischen Ambulanz soll die Wirksamkeit des EPK bei der Therapie der Eisenmangelanämie mit aktuellen Ergebnissen unterstrichen werden. Patienten, Methode: Es erfolgte eine retrospektive Analyse von 57 Patienten (Alter: 5–185 Monaten) mit der Diagnose Eisenmangelanämie, die mit EPK behandelt wurden. Ergebnisse: Die EPK-Therapie führte zu signifikanten Veränderungen von Hämoglobin, Hämatokrit, MCV, Serumferritin und löslichem Transferrinrezeptor (sTFR) sowie des sTFR-Index. Bis auf zwei Fälle von Obstipation traten keine unerwünschten Arzneimittelwirkungen auf. Schlussfolgerung: Die Therapie der Eisenmangelanämie mit EPK ist im Alltag der pädiatrischen Praxis erfolgreich und gut verträglich. Sie bietet eine effektive therapeutis...
Introduction: Hepatic siderosis, a result of chronic transfusion therapy, leads to hepatocellular... more Introduction: Hepatic siderosis, a result of chronic transfusion therapy, leads to hepatocellular injury and progression to chronic liver disease. Increases in serum transaminase levels are indicative of progressive liver damage. The effect of deferasirox (Exjade®, ICL670), a novel, once-daily oral chelator, on liver iron content and pathology in chronically transfused patients has been assessed in Phase II and III clinical studies. A sub-analysis of pooled data from the planned 4-year extension of two pivotal studies sought to correlate the long-term changes in serum ALT levels with those of serum ferritin in iron-overloaded patients during treatment with deferasirox. Methods: In these two clinical studies, 480 patients with β-thalassemia (β-thal), myelodysplastic syndromes (MDS), Diamond-Blackfan anemia (DBA), and other transfusion-dependent anemias received deferasirox at 5, 10, 20 or 30 mg/kg/day according to baseline liver iron concentrations for 12 months. In the extension pha...
Erythrocytosis is a rare disorder characterized by increased red cell mass and elevated hemoglobi... more Erythrocytosis is a rare disorder characterized by increased red cell mass and elevated hemoglobin concentration and hematocrit. Several genetic variants have been identified as causes for erythrocytosis in genes belonging to different pathways including oxygen sensing, erythropoiesis and oxygen transport. However, despite clinical investigation and screening for these mutations, the cause of disease cannot be found in a considerable number of patients, who are classified as having idiopathic erythrocytosis. In this study, we developed a targeted next generation sequencing panel encompassing the exonic regions of 21 genes from relevant pathways (~79Kb) and sequenced 125 patients with idiopathic erythrocytosis. The panel effectively screened 97% of coding regions of these genes, with an average coverage of 450X. It identified 51 different rare variants, all leading to alteration of protein sequence, with 57 out of 125 cases (45.6%) having at least 1 of these variants. Ten of these we...
Concurrent emergence of nephroblastoma (Wilms Tumor; WT) and neuroblastoma (NB) is rare and mostl... more Concurrent emergence of nephroblastoma (Wilms Tumor; WT) and neuroblastoma (NB) is rare and mostly observed in patients with severe subtypes of Fanconi anemia (FA) with or without VACTER-L association (VL). We investigated the hypothesis that early consequences of genomic instability result in shared regions with copy number variation in different precursor cells that originate distinct embryonal tumors. We observed a newborn girl with FA and VL (aplasia of the thumbs, cloacal atresia (urogenital sinus), tethered cord at L3/L4, muscular ventricular septum defect, and horseshoe-kidney with a single ureter) who simultaneously acquired an epithelial-type WT in the left portion of the kidney and a poorly differentiated adrenal NB in infancy. A novel homozygous germline frameshift mutation in PALB2 (c.1676_c1677delAAinsG) leading to protein truncation (pGln526ArgfsX1) inherited from consanguineous parents formed the genetic basis of FA-N. Spontaneous and induced chromosomal instability w...
At present, about 300 patients with thalassemia major are living in Germany. Starting in 1991, a ... more At present, about 300 patients with thalassemia major are living in Germany. Starting in 1991, a multicenter study in Germany has concentrated on identifying all patients suffering from thalassemia as well as on establishing a uniform therapy protocol including follow-up diagnostic procedures. After six years of study, the data of 198 patients suffering from thalassaemia major were analysed. The majority of these patients originate from endemic regions around the Mediterranean Sea. The patient's median age is 13.8 years (range 1-37.5 yrs.). At present, about 20% of patients are older than 21 years. Regarding transfusion therapy, a shortening of the average transfusion interval to 3 weeks in most cases occurred. Throughout the entire period, median baseline haemoglobin concentrations of 10.0 g/dl could be observed. The evaluation of serum ferritin levels revealed considerable differences depending on patients age. 60% of patients in the first decade of life showed good therapeuti...
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