Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expanded lymphocyte population in large granular lymphocyte (LGL)-leukemia carries the phenotypic characteristics of either cytotoxic T lymphocytes (CD3+,CD8+) or natural killer (NK) cells (CD3-,CD15+). In the former subset, clonality has been demonstrated by T-cell receptor gene rearrangement studies. Since NK cells do not rearrange T-cell receptor genes, the neoplastic nature of chronic NK cell lymphocytosis has not been well defined. We used X-linked DNA analysis to study the clonal nature of an expanded NK cell population in a patient with a 3-year history of relative lymphocytosis associated with anemia and neutropenia. Southern blot analysis showed no clonal T-cell receptor gene rearrangement. The majority of the circulating lymphocytes had a NK cell phenotype and demonstrated both direct NK cell-mediated cytotoxicity and antibody-dependent cellular cytotoxicity. However, the in vitro growth characteristics of these cells did not suggest that they were polyclonal expansions of normal NK cells. To determine directly the clonal origin of these cells, we performed X-linked DNA analysis. Density gradient centrifugation methods were used to isolate mononuclear cells, and NK cells were positively selected by CD16-immunoconjugated magnetic beads. The DNA of these cells was analyzed by restriction fragment length polymorphism-methylation strategy and showed a monoclonal pattern of X-chromosome inactivation while a polyclonal pattern was obtained in corresponding skin tissue. Treatment of the patient with oral cyclophosphamide resulted in complete hematologic remission. We conclude that chronic NK lymphocytosis may be clonal and responsive to immunosuppressive therapy.
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PMID:Demonstration of clonality, by X-linked DNA analysis, in chronic natural killer cell lymphocytosis and successful therapy with oral cyclophosphamide. 135 Jun 51

A 60-year-old part Aboriginal woman was observed to develop severe neutropenia and a large granular lymphocyte (LGL) proliferation five years after the diagnosis of systemic lupus erythematosus (SLE). Monoclonality of the CD3+, CD4-, CD8+ LGL population was confirmed using the novel approach of X-linked restriction fragment length polymorphism (RFLP) analysis. Indeterminate HTLV-I serology was present. The patient responded to steroid therapy. LGL proliferation in the setting of SLE and the use of X-linked RFLP analysis to define LGL clonality have not previously been reported.
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PMID:Monoclonal large granular lymphocyte proliferation in SLE with HTLV-I seroreactivity. 158 Aug 66

Seven boys with an apparently X-linked syndrome of dilated cardiomyopathy, growth retardation, neutropenia, and persistently elevated urinary levels of 3-methylglutaconate, 3-methylglutarate, and 2-ethylhydracrylate were studied. The natural history of the disorder was characterized by severe or lethal cardiac disease and recurrent infections during infancy and early childhood but relative improvement in later childhood. The initial presentation of the syndrome varied from congenital dilated cardiomyopathy to infantile congestive heart failure to isolated neutropenia without clinical evidence of heart disease. The excretion of 3-methylglutaconate and 3-methylglutarate appeared to be independent of the metabolism of leucine, the presumed precursor of these organic acids in humans. Although the cause of the organic aciduria remains obscure, the constellation of biochemical and clinical abnormalities forms a distinct syndrome that may be a relatively common cause of dilated cardiomyopathy or neutropenia in boys during infancy and childhood.
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PMID:X-linked dilated cardiomyopathy with neutropenia, growth retardation, and 3-methylglutaconic aciduria. 171 74

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

X-linked cardioskeletal myopathy with neutropenia and abnormal mitochondria is clinically characterized by congenital dilated cardiomyopathy, skeletal myopathy, recurrent bacterial infections, and growth retardation. We analyzed linkage between the disease locus and X-chromosomal markers in a family with seven carriers, four patients, and eight unaffected sons of carriers. Highest lod scores obtained by two-point linkage analysis were 2.70 for St14.1 (DXS52, TaqI) at a recombination fraction of zero and 2.53 for cpX67 (DXS134) at a recombination fraction of zero. Multipoint linkage analysis resulted in a maximum lod score of 5.24 at the position of St35.691 (DXS305). The most distal recombination detected in this family was located between the markers II-10 (DXS466) and DX13 (DXS15). These data indicate the location of the mutated gene at Xq28.
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PMID:Mapping of the locus for X-linked cardioskeletal myopathy with neutropenia and abnormal mitochondria (Barth syndrome) to Xq28. 199 34

Hyper IgM with low IgG and IgA is a rare humoral immunodeficiency. We presently report 12 new observations which have been clinically and immunologically studied. On one occasion the syndrome was found to be associated with congenital rubella. Since 10/12 children were male, X-linked inheritance is suggested which has been confirmed in 2 cases. In most cases (9/12), the first infections occurred within the first year of life. The syndrome is causing upper and lower respiratory tract infections due to bacteria, as well as gut infections. Lymphoid organ hyperplasia has been noted in 11/12 patients. Polyclonal hyper IgM serum contrasts with low or absent IgG, IgA and IgE. In some instances, some IgM antibody response was detected. A dysfunction of cellular immunity was not detected. Autoimmunity was detected in 3 patients. Finally, transient neutropenia occurred in 50% of the patients. Intravenous immunoglobulin G substitution treatment resulted in a significant reduction in the occurrence of infections as well as in normalization of growth rate. Immunoglobulin infusion also frequently induced correction of hyper IgM and neutropenia.
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PMID:[Hypogammaglobulinemia G and A with hypergammaglobulinemia M. Apropos of 12 cases]. 236 67

A kindred is described in which neutropenia and low serum immunoglobulin A levels has occurred. The affected members have variable clinical courses which do not appear to relate to the degree of neutropenia. The bone marrows show a maturation delay in granulocyte production, with increased numbers of lymphocytes. In vitro cultures of the bone marrows failed to produce granulocyte colonies. Studies of peripheral blood and bone marrow lymphocyte subpopulations give inconsistent results, although a general increase in T suppressor lymphocytes compared with T helper lymphocytes emerges. A therapeutic trial of corticosteroid and then of lithium carbonate was without effect on one of the patients. The pathogenetic basis for this probably X-linked disorder remains unclear.
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PMID:Congenital neutropenia and low serum immunoglobulin A: description and investigation of a large kindred. 328 30

An X-linked recessive disease is reported in a large pedigree. The disease is characterised by a triad of dilated cardiomyopathy, neutropenia and skeletal myopathy. The untreated patients, all boys, died in infancy or early childhood from septicemia or cardiac decompensation. Ultrastructural abnormalities were observed in mitochondria in cardiac muscle cells, neutrophil bone marrow cells and to a lesser extent (0-9%) in skeletal muscle cells. Membrane-bound vacuoles were seen in neutrophil bone marrow cells. Intramuscular fat droplets were increased in type I skeletal muscle fibres. An affected patient had intermittent lactic acidemia, borderline low plasma carnitine, the latter decreasing during periods of illness, and low muscle carnitine (27% pretreatment; 35-40% posttreatment). While on treatment with oral carnitine he had less weakness and no cardiac complaints, but his neutropenia was not affected. Respiratory chain abnormalities were observed in this patient's isolated skeletal muscle mitochondria. These were: (1) diminished concentrations of cytochromes c1 + c, b and aa3 to 29, 47 and 64% of the averaged controls, and (2) a lowered P:0 ratio for oxidation of ascorbate + TMPD, with diminished uncoupler stimulated Mg2+-ATPase activity. Muscle AMP deaminase was deficient (5 resp. 17%). Only one previous report (Neustein et al. 1979) on X-linked mitochondrial cardiomyopathy exists, which probably refers to the same entity. Biochemical studies and haematological abnormalities (neutropenia) are reported for the first time.
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PMID:An X-linked mitochondrial disease affecting cardiac muscle, skeletal muscle and neutrophil leucocytes. 614 97

In a family of 5 boys and 6 girls, 3 brothers have clinical dyskeratosis congenita. Teeth from 2 of the patients were taurodent , and mineral density of the enamel was significantly different from normal. The haematopoietic marrow was hypocellular and there was striking prominence of plasma cells having normal morphology; no granulomata were demonstrated. The decreased erythroid precursors in the marrow correlated with quantitatively reduced erythropoiesis demonstrated on ferrokinetic studies. Recurrent infections occurred but could not be related to neutropenia, and granulocytes and monocytes retained normal function. No abnormality was demonstrated in humoral or cellular immune mechanisms. While superficially similar, dyskeratosis congenita and Fanconi's anaemia are genetically distinct, being X-linked in the former and inherited as an autosomal recessive in the latter.
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PMID:Dyskeratosis congenita. Haematologic, cytogenetic, and dermatologic studies. 653 99

Three distinct clinical syndromes occur in patients with increased numbers of circulating LGL. Patients with T-LGL leukemia have clonal proliferations of CD3+ LGL typically associated with chronic neutropenia and autoimmune features. NK-LGL leukemia is characterized by clonal CD3- LGL proliferation with an acute clinical presentation marked by massive hepatosplenomegaly and systemic illness. However, most patients with increased numbers of CD3- LGL do not have clinical features of NK-LGL leukemia and have a chronic clinical course. X-linked gene analyses have supported a polyclonal LGL lymphocytosis in this syndrome. Further studies are needed to determine whether clonal progression can occur in these patients.
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PMID:Clonal diseases of large granular lymphocytes. 827 46


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