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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In patients with hereditary haematologic diseases risk of repetition of these anomalies in brothers and sisters of probands and their progenies was assessed. In haemiphilia and Wiskott-Aldrich's. thrombocytopenia, both caused by a mutant gene in an X chromosome, prenatal pole determination was consulted in order to have a pregnancy with a male fetus interrupted due to high risk. Dominantly hereditary spherocytosis, eliptocytosis, chronic benign neutropenia are the diseases which do not appear in such a severe form that ceasation of further pregnancies should be consulted, instead, an early postnatal diagnosis is suggested to the families with increased risk of these anomalies. In the recessive hereditary beta thalassemia and in Fanconi's anemia in which prenatal diagnosis can not be made for the time being, level of risk for the further children is told to the parents after the child has been born. The parents are then left to decide whether to take a risk and have other children who might suffer of these severe haemolitic diseases. In the haemolitic diseases with often occurrence in certain families, but in which the manner of inheritance is not clear, as for example in the Kasebach-Meritt's syndrome, risk for the following children is uncertainly increased so that the genetic counsel is uncertain and unprecise. In the hereditary haemolitic diseases which appear sporadically, either of known or unknown etiology, such as congenital teleangiectasis of capillary vessels or Sturge-Weber's syndrome with severe vascular and nerval disorders, the parents are stimulated to further pregnancies as they are not followed by increased risk.
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PMID:[Genetic counseling in hematologic diseases]. 61 9

Congenital thrombocytopenia may occur in isolation or accompanied by eczema and immunodeficiency, as part of the X-linked hereditary Wiskott-Aldrich syndrome (WAS). Because the clinical and immunologic picture of WAS is variable, particularly early in life, definite diagnosis cannot always be made in cases with a negative family history. Two unrelated males with sporadic congenital thrombocytopenia had only questionable immunologic abnormalities as infants, making them clinically indistinguishable from cases of isolated thrombocytopenia, although one developed episodic neutropenia and the other began to manifest a multisystem autoimmune disease at 2 years of age. Evaluation of X chromosome inactivation in the T cells of both patients' mothers showed each of these women to have the same highly skewed X chromosome inactivation pattern seen in carriers of typical familial WAS. A T-cell defect was subsequently directly demonstrated in the second patient, whose lymphocytes failed to proliferate to periodate and anti-CD43. Taken together, these data suggest the presence of T cell immunodeficiency consistent with WAS in these patients. Furthermore, their mothers were found to have a very high likelihood of being carriers, lending support to the diagnosis of a hereditary disease in these boys and making possible genetic prediction in other family members and subsequent pregnancies.
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PMID:Atypical presentation of Wiskott-Aldrich syndrome: diagnosis in two unrelated males based on studies of maternal T cell X chromosome inactivation. 199 98

Ninety-one congenitally immunodeficient patients treated from 1972 to 1981 were reviewed to assess the incidence and nature of gastrointestinal complications. Thirty-three of these patients (36%) developed 59 complications. Patients with immunodeficiencies characterized by neutrophil dysfunction--chronic granulomatous disease (20 patients) and cyclic neutropenia (eight patients)--developed 22 surgical infections, 22 of which required operation. In patients with neutrophil defects, postoperative morbidity was frequent and severe. Gastrointestinal symptoms were common in patients with isolated defects of B or T lymphocytes. Ten of forty-one patients with congenital hypogammaglobulinemia developed gastrointestinal complications, as did one of four patients with DiGeorge Syndrome, and the single patient with secretory IgA deficiency. However, operation was not required for these patients with isolated disorders of lymphocyte function. Patients with combined B and T cell disorders developed gastrointestinal disease, requiring operative therapy at intermediate rates. Gastrointestinal symptoms developed in four of nine patients with severe combined immunodeficiency and three of eight with Wiskott-Aldrich syndrome. Operative therapy was required in two of these seven symptomatic patients.
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PMID:Gastrointestinal complications of congenital immunodeficiency states. The surgeon's role. 660 28

A 2 3/4 year old male with thrombocytopenia secondary to Wiskott-Aldrich Syndrome (WAS) and a history of two intracranial hemorrhages as well as hemolytic anemia and neutropenia received a placental blood infusion from an HLA-identical female sibling born by caesarian section at 35 weeks gestation. The patient was prepared with Thiotepa and Cytoxan and received a nucleated cell dose of 3.0 x 10(7)/kg. Cyclosporin A and Methylprednisolone was given for graft versus host disease (GVHD) prophylaxis. An ANC of 0.5 x 10(9)/L and 1.0 x 10(9)/L were achieved on post-transplant days 18 and 28, respectively. Platelet recovery was rapid with a platelet count > or = 100 x 10(9)/L on day +39. On posttransplant day +11, the patient developed an erythematous rash consistent with grade I acute GVHD that resolved without therapy. He was discharged day on +60 and has remained free of infections with a normal platelet count off all immunosuppression therapy 30+ months post-transplantation. Chimerism studies performed on peripheral blood mononuclear cells by fluorescent in situ hybridization indicated that the percentage of donor cells ranged between 55 and 80%. The phenotype and function of peripheral blood lymphocytes are completely normal and the patient has responded in vivo with production of antibodies to both diphtheria and tetanus immunizations. This study demonstrates the feasibility of collecting placental blood after a multiple birth delivery and the ability of umbilical cord blood to provide complete hematopoietic and immunologic reconstitution in a patient with WAS.
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PMID:Umbilical cord blood infusion in a patient for correction of Wiskott-Aldrich syndrome. 774 1

A 7-month-old patient with Wiskott-Aldrich syndrome (WAS) developed pneumatosis intestinalis (PI) in the immediate post-transplant period after receiving paternal human leucocyte antigen (HLA) phenotypically matched bone marrow (BM). PI has been described in patients with congenital or acquired immunodeficiency states and after bone marrow transplantation (BMT). To our knowledge, the condition has not been described in WAS. The underlying bowel mucosa damage as a result of the history of massive rectal bleeding, the effects of the conditioning regimen, immunosuppression, neutropenia, and infection, may all have contributed to the development of PI. Although the condition resolved by conservative management alone, the patient developed Klebsiella pneumonia sepsis, interstitial pneumonitis, failed to engraft, and died on day +66 following a second infusion of stem cells mobilized from his father's peripheral blood.
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PMID:Pneumatosis intestinalis in an infant undergoing bone marrow transplantation for Wiskott-Aldrich syndrome. 1156 Jul 58

Mutations of the WASP gene have been previously shown to be responsible for classical Wiskott-Aldrich syndrome, isolated X-linked thrombocytopenia, and severe, congenital X-linked neutropenia. We report herewith 2 families in which affected males had a history of intermittent thrombocytopenia with consistently reduced platelet volume, in the absence of other major clinical features, and carried missense mutations of the WASP gene that allowed substantial protein expression. This observation broadens the spectrum of clinical phenotypes associated with WASP gene defects, and it indicates the need for molecular analysis in males with reduced platelet volume, regardless of the platelet number.
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PMID:Missense mutations of the WASP gene cause intermittent X-linked thrombocytopenia. 1187 12

There have been many recent advances in our understanding of the molecular basis of neutropenia disorders, primarily through advances in genetic analysis of inherited disorders. Molecular and cellular studies now suggest that accelerated apoptosis of neutrophil precursors in the bone marrow is the common pathophysiologic mechanism. Severe congenital neutropenia and cyclic neutropenia, both usually inherited as autosomal-dominant disorders, are caused by mutations in the neutrophil elastase gene. Myelokathexis is attributed to the downregulation of the bcl-x protein, but the genetic basis is not yet known. The genes for several diseases with more complex phenotypes (eg, glycogen storage disease type 1b, Chediak-Higashi syndrome, Shwachman-Diamond syndrome, dyskeratosis congenita, Griscelli syndrome, Barth syndrome, and Wiskott-Aldrich syndrome) have all been identified recently. The molecular mechanisms for most acquired disorders causing neutropenia (eg, idiopathic neutropenia, pure white-cell aplasia, myelodysplasia, and aplastic anemia) are not yet known. Granulocyte colony stimulating factor (G-CSF) is effective treatment for several of these conditions. Through better understanding of these disorders, we anticipate that better treatments will be found in the future.
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PMID:Molecular basis and therapy of disorders associated with chronic neutropenia. 1290 73

The identification of chemokines has profoundly changed the way we interpret the immune response, elucidating the mechanism by which inflammatory cells are recruited to the site of infection by local secretion of chemoattractants such as CXC chemokine ligand 8 (CXCL8)/interleukin-8, chemokine ligand 2 (CCL2)/monocyte chemoattractant protein 1. This novel view of the immune response has been remodeled further following observations that lymphoid tissue development derives from the coordinated secretion of homeostatic chemokines such as CCL19, CCL21, and CXCL13, which mediate recruitment and clustering of the cells involved in lymphoid organogenesis. The study of primary immunodeficiencies has demonstrated that the number of circulating leukocytes is dependent on migration amongst bone marrow, blood circulation, and inflamed tissues. Defects of leukocyte adhesion and chemotaxis as a result of mutations of beta2-integrins lead to abnormal leukocytosis and susceptibility to skin infections, as observed in leukocyte adhesion deficiency. Conversely, neutropenia in children with myelokathexis is a result of leukocyte retention in the bone marrow because of the mutations of CXC chemokine receptor 4, which affect the capacity of cells to recirculate between blood and bone marrow. Moreover, the identification of the genetic basis of primary immunodeficiencies has shown that many primary immunodeficiencies such as Wiskott-Aldrich syndrome and common variable immunodeficiencies are characterized by altered migration of leukocytes and/or disregulation of cellular response to chemokines. This paper will be focused on the interpretation of primary immunodeficiencies as defects in leukocyte circulation between blood and primary and secondary organs.
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PMID:Leukocyte circulation: one-way or round-trip? Lessons from primary immunodeficiency patients. 1507 52

The Wiskott-Aldrich syndrome (WAS) is a rare X-linked disorder with variable clinical phenotypes that correlate with the type of mutations in the WAS protein (WASP) gene. WASP, a key regulator of actin polymerization in hematopoietic cells, has 5 well-defined domains that are involved in signaling, cell locomotion, and immune synapse formation. WASP facilitates the nuclear translocation of nuclear factor kappaB and was shown to play an important role in lymphoid development and in the maturation and function of myeloid monocytic cells. Mutations of WASP are located throughout the gene and either inhibit or dysregulate normal WASP function. Analysis of a large patient population demonstrates a phenotype-genotype correlation: classic WAS occurs when WASP is absent, X-linked thrombocytopenia when mutated WASP is expressed, and X-linked neutropenia when missense mutations occur in the Cdc42-binding site. The progress made in dissecting the function of WASP has provided new diagnostic possibilities and has propelled our therapeutic strategies from conservative symptomatic treatment to curative hematopoietic stem cell transplantation and toward gene therapy.
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PMID:The Wiskott-Aldrich syndrome. 1663 Sep 28

Severe congenital neutropenia (SCN) is characterized by neutropenia, recurrent bacterial infections, and maturation arrest in the bone marrow. Although many cases have mutations in the ELA2 gene encoding neutrophil elastase, a significant proportion remain undefined at a molecular level. A mutation (Leu270Pro) in the gene encoding the Wiskott-Aldrich syndrome protein (WASp) resulting in an X-linked SCN kindred has been reported. We therefore screened the WAS gene in 14 young SCN males with wild-type ELA2 and identified 2 with novel mutations, one who presented with myelodysplasia (Ile294Thr) and the other with classic SCN (Ser270Pro). Both patients had defects of immunologic function including a generalized reduction of lymphoid and natural killer cell numbers, reduced lymphocyte proliferation, and abrogated phagocyte activity. In vitro culture of bone marrow progenitors demonstrated a profound reduction in neutrophil production and increased levels of apoptosis, consistent with an intrinsic disturbance of normal myeloid differentiation as the cause of the neutropenia. Both mutations resulted in increased WASp activity and produced marked abnormalities of cytoskeletal structure and dynamics. Furthermore, these results also suggest a novel cause of myelodysplasia and that male children with myelodysplasia and disturbance of immunologic function should be screened for such mutations.
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PMID:Two novel activating mutations in the Wiskott-Aldrich syndrome protein result in congenital neutropenia. 1680 17


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