Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038002 (splenomegaly)
 9,873 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Congenital neutropenia (CN) includes hematologic disorders characterized by severe neutropenia with an absolute neutrophil count (ANC) below 0.5 x 10(9)/L associated with severe systemic bacterial infections from early infancy. One subtype of CN, Kostmann syndrome, was originally described as an autosomal-recessive disorder, characterized by early-stage maturation arrest of myelopoiesis. Autosomal-dominant and sporadic cases have also been reported. Recent studies on the genetic bases of CN have detected different inherited or spontaneous point mutations in the neutrophil elastase gene. Development of additional genetic defects during the course of disease, such as granulocyte colony-stimulating factor (G-CSF)-receptor gene mutations and cytogenetic aberrations, indicates an underlying genetic instability. Data on more than 300 patients with CN collected by the Severe Chronic Neutropenia International Registry (SCNIR) since 1994 demonstrate that, independent of the CN subtype, more than 90% of patients respond to recombinant human (rHu)G-CSF with ANCs that can be maintained at approximately 1.0 x 10(9)/L. Adverse events include mild splenomegaly, moderate thrombocytopenia, osteoporosis, and malignant transformation into myelodysplasia (MDS)/leukemia. If and how rHuG-CSF treatment impacts on these adverse events remains unclear since there are no historical controls for comparison. Hematopoietic stem cell transplantation (HSCT) is still the only available treatment for patients refractory to rHuG-CSF treatment.
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PMID:Kostmann syndrome and severe congenital neutropenia. 1195 89

The term congenital neutropenia (CN) has been used for a group of hematologic disorders characterized by severe neutropenia with absolute neutrophil counts (ANC) below 0.5 x 10(9)/L associated with increased susceptibility to bacterial infections. This group of diseases includes primary bone marrow failure syndromes with isolated neutropenias and neutropenias associated with metabolic or immunologic disorders or with a complex syndrome. To avoid confusion, we prefer using the term CN only for the most severe disorder among this group: severe neutropenia characterized by an early stage maturation arrest of myelopoiesis leading to bacterial infections from early infancy. This disease has originally been described as Kostmann syndrome with an autosomal recessive inheritance. Recent pathogenetic investigations have demonstrated that this clinical phenotype includes also autosomal dominant and sporadic cases with different point mutations in the neutrophil elastase gene in a subgroup of patients. Data on over 400 patients with CN collected by the Severe Chronic Neutropenia International Registry demonstrate that independent from the CN-subtype more than 90% of these patients respond to recombinant human granulocyte-colony stimulating factor (rHuG-CSF filgrastim, lenograstim) with ANC that can be maintained around 1.0 x 10(9)/L. Adverse events include mild splenomegaly, moderate thrombocytopenia, osteoporosis and malignant transformation into myelodysplastic syndrome/leukemia. Development of additional genetic aberrations, e.g., G-CSF-receptor gene mutations, monosomy 7 or ras mutations during the course of the disease indicate an underlying genetic instability leading to an increased risk of malignant transformation. If and how G-CSF treatment impacts on these adverse events remains unclear since there are no historical controls for comparison. Hematopoietic stem cell transplantation is still the only available treatment for patients refractory to G-CSF treatment.
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PMID:Congenital neutropenias. 1469 35

Severe congenital neutropenia (CN) includes a variety of hematologic disorders characterized by severe neutropenia, with absolute neutrophil counts (ANC) below 0.5 x 10(9)/L, and associated with severe systemic bacterial infections from early infancy. One subtype of CN, Kostmann syndrome, is an autosomal recessive disorder, characterized histopathologically by early-stage maturation arrest of myeloid differentiation. CN with similar clinical features occurs as an autosomal dominant disorder and many sporadic cases also have been reported. This genetic heterogeneity suggests that several pathophysiological mechanisms may lead to this common clinical phenotype. Recent studies on the genetic bases of CN have detected inherited or spontaneous point mutations in the neutrophil elastase gene (ELA 2) in about 60% to 80% of patients and, less commonly, mutations in other genes. Acquisition of additional genetic defects during the course of the disease, for example, granulocyte colony-stimulating factor (G-CSF) receptor gene mutations and cytogenetic aberrations, indicates an underlying genetic instability as a common feature for all congenital neutropenia subtypes. Data on more than 600 patients with CN collected by the Severe Chronic Neutropenia International Registry (SCNIR) demonstrate that, regardless of the particular CN subtype, more than 95% of these patients respond to recombinant human (rHu)G-CSF with ANCs that can be maintained above 1.0 x 10(9)/L. Adverse events include mild splenomegaly, osteoporosis, and malignant transformation into myelodysplasia (MDS)/leukemia. If and how G-CSF treatment impacts on these adverse events is not fully understood. In recent analyses the influence of the G-CSF dose required to achieve neutrophil response (ANC >1,000/microL) in the risk of developing acute myeloid leukemia (AML) has been reported. Hematopoietic stem cell transplantation (HSCT) is still the only treatment available for patients who are refractory to G-CSF treatment.
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PMID:Severe congenital neutropenia. 1682 61