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

Among Ashkenazi-Jews, Gaucher' disease, an autosomal-recessive hereditary genetic defect of sphingolipid metabolism, occurs more frequently than in the general population. Because of lack of the specific b-glucosidase, glucocerebrosidase, there is increased deposition of glucocerebrosides in the reticulo-endothelial system, mostly in the spleen, liver, and bone-marrow. In the chronic adult form (type 1), in addition to the hematologic complications (which are mostly associated with a splenomegaly), a less known involvement of the skeletal system occurs, which can lead to significant rheumatologic and orthopedic problems. These are: nonspecific skeletal and joint pain, purulent osteomyelitis, pseudo-osteomyelitis, aseptic necrosis of the femoral head, pathologic fractures of the long bones, acutely occurring kyphosis secondary to pathologic vertebral fractures with or without spinal compression, bony deformities, growth disturbances, arthritis, and bursitis. One sees a wide variety of bone lesions which can be solitary or multiple. Various pathogenic mechanisms have been discussed: toxic reaction to the Gaucher cells, disturbance of the osteoblastic and osteoclastic function, compression of osseous blood vessels by pathological cells, pressure-induced atrophy of the surrounding osseous tissue, local hemorrhage, local thrombosis, invasion of the arterioles with subsequent occlusion, and bone infarcts. The therapy is purely symptomatic. For orthopedic problems there is a greater tendency towards conservative treatment. There is disagreement as to whether splenectomy, which is often performed for hematologic or mechanical reasons, accelerates involvement of the bone. The case of a patient with multiple fractures of the spine and a slight spinal compression is presented.
 ...
PMID:[Bone changes in Gaucher disease]. 262 78

Gaucher's disease is an autosomal recessive disorder caused by deficiency of beta glucocerebrosidase, resulting in an accumulation of glucocerebroside in the reticuloendothelial system. These patients have massive splenomegaly and bone pain, but may have normal life expectancy. Traditionally, splenectomy has been used to treat hypersplenism, but may be associated with a high incidence of postsplenectomy sepsis and accelerated hepatic and bone lipid deposition. Two children are reported who had partial splenectomy for symptoms of Gaucher's disease. Both patients had laboratory evidence of hypersplenism. A 90% splenectomy was performed, and the residual splenic fragment was wrapped in Vicryl mesh. Both patients are currently asymptomatic with normal hematologic parameters. Postoperative radionuclide scans demonstrate increase in the size of the residual splenic fragment. Partial splenectomy may benefit patients with Gaucher's disease, but long-term follow-up care is necessary.
 ...
PMID:Partial splenectomy for Gaucher's disease. 359 12

Two Nigerian sibling presented with progressive hepato-splenomegaly in infancy from which they subsequently died. Morphological investigations carried out showed that the children had Gaucher's disease. Leucocyte B-glucocerebrosidase activities from the parents of the two siblings and also from one surviving sibling were found to be only about 50% of the enzyme activities in control subjects while hexosaminidase and B-glucuronidase activities were within normal limits. There results showed that the three surviving relatives are heterozygotes and also provided a strong supporting evidence that the deceased children had Gaucher's disease. The occurence of this disease in African children living in Kenya, Uganda, the Congo and Nigeria, and in Black Americans suggest that this biochemical abnormality is not as rare in the Negroid race as has been believed hitherto, and may be widespread on the African continent.
 ...
PMID:Gaucher's disease: a clinical, morphological and biochemical study of a Nigerian family. 628 83

Concentrations of IgA, IgG, and IgM were measured in 25 patients with Gaucher's disease. The mean of each was significantly higher than that generally observed in healthy adults. A direct correlation was noted between IgA and IgG concentrations and age. Patients who underwent splenectomy had IgM concentrations significantly lower than those of persons who did not. In two of 25 patients, multiple myeloma of the nonsecretory type developed. The migration inhibition factor (MIF) test performed with the lymphocytes of our patients was positive to glucocerebroside in four of 17 patients, to glucocerebrosidase in four of 19 patients, and to the extracts of the spleen of a patient with Gaucher's disease in three of eight patients. The results of al MIF tests were negative in six control subjects with splenomegaly of other causes. Our results suggest that in Gaucher's disease there is chronic stimulation of the humoral immune system. The first expression of this stimulation is the production of polyclonal immunoglobulins and, in due time, the development of monoclonal immunoglobulin as well as multiple myeloma.
 ...
PMID:Gaucher's disease: a disease with chronic stimulation of the immune system. 704 16

Enzyme replacement therapy is highly effective for patients with Type 1 Gaucher disease. In order to estimate the quantity of enzyme that would be necessary for clinical benefit, we conducted a single-infusion, dose-response study in nonsplenectomized patients with Gaucher disease. Biochemical and histologic changes were compared in liver biopsy specimens obtained before and 44 h following the infusion of varying quantities of enzyme. Based on the information obtained from this investigation, patients in our initial clinical efficacy trial were given 60 IU of macrophage-targeted glucocerebrosidase/kg body wt every other week. All patients had significant improvement of their anemia and reduction of splenomegaly after 6 months of treatment. In a subsequent investigation, 10 moderately symptomatic patients with intact spleens were given 10 IU of glucocerebrosidase/kg body wt every other week. After 6 months of treatment, only a portion of these patients had beneficial responses. We concluded that the rate and extent of response to enzyme replacement therapy in patients with Gaucher disease are dependent upon the quantity of enzyme administered. When treatment is initiated in patients with mild to moderately severe disease, a lower dose of enzyme can be selected. Moreover, the maintenance dose of glucocerebrosidase has been shown to be much less than the amount initially required to reduce the accumulated lipid. Some patients require enzyme infusions on only a monthly basis, require enzyme infusions on only a monthly basis, and it is possible that even this frequency may eventually be reduced. These refinements in treatment strategy merit serious consideration for the long-term management of patients with Gaucher disease.
 ...
PMID:Enzyme replacement therapy for Gaucher disease: critical investigations beyond demonstration of clinical efficacy. 791 61

Gaucher disease, the most common form of lysosomal storage disease, is the result of autosomal recessive inheritance of a lysosomal enzyme glucocerebrosidase deficiency, which produces defective hydrolysis of glucosylceramide that accumulates in reticuloendothelial (tissue macrophage) cells. The current review focuses on Type 1 (the nonneuronopathic) or adult Gaucher disease and defines the clinical manifestations (splenomegaly, hepatomegaly, bony lesions, and clinical metabolic dysfunction) in relationship to the known enzymatic defect. The clinical diversity and variability in symptoms and signs, the age at onset of the clinical manifestations and their rate of progression, and the heterogeneity of the organs involved are reviewed. Extensive delineation of the nature of the enzyme defect and the recent molecular characterization of the enzyme mutants has not provided an explantation for the remarkable clinical phenotypic heterogeneity. Enzyme assays now provide an excellent method for diagnosis. Effective enzyme replacement therapy emphasizes the value of early diagnosis and has altered the costs and potential risks of older therapeutic indications for splenectomy or cytokine therapy. Enzyme efficacy raises questions about the specific indications for replacement treatment and the most desirable rate and duration of enzyme delivery.
 ...
PMID:Gaucher disease: a heterogeneous clinical complex for which effective enzyme replacement has come of age. 809 3

Gaucher disease is the most prevalent hereditary metabolic storage disorder, and the most common genetic disease in individuals of Ashkenazic Jewish ancestry. Patients with Gaucher disease have been classified into three clinical phenotypes. Patients with type 1 disease exhibit markedly variable hepatosplenomegaly, anemia, thrombocytopenia, skeletal, and, to a lesser extent, pulmonary and kidney involvement. The central nervous system does not appear to be involved. In patients with type 2 Gaucher disease, hepatosplenomegaly and extensive central nervous system damage are apparent in infancy. These patients usually die between 1 and 2 years of age. Patients with type 3 Gaucher disease have been subclassified into types 3a and 3b. Type 3a patients exhibit mild-to-moderate hepatosplenomegaly and slowly progressive neurologic deterioration. Recurrent myoclonic seizures are common. Patients with type 3b Gaucher disease exhibit splenomegaly along with extensive hepatomegaly that is frequently accompanied by esophageal varices. Horizontal supranuclear gaze paresis is the major neurologic sign. Excessive quantities of glucocerebroside accumulate in the organs of patients with Gaucher disease because of a deficiency of the enzyme glucocerebrosidase. In the vast majority of patients, the reduction of glucocerebrosidase activity is caused by mutations in the gene that codes for glucocerebrosidase. In a few instances, glucocerebroside accumulates due to a lack of saposin C, a cohydrolase that is required in addition to glucocerebrosidase for the catabolism of glucocerebroside. Mutations in the glucocerebrosidase gene are discussed in the context of the severity of disease and the presence or absence of nervous system involvement. Enzyme replacement therapy is highly beneficial for patients with type 1 Gaucher disease. Enzyme replacement is also being investigated for patients with type 3b Gaucher disease. Novel procedures must be developed to deliver glucocerebrosidase to the nervous system so that patients with type 2 and type 3a Gaucher disease can be helped. Exploration of gene therapy for Gaucher disease is under way.
 ...
PMID:The role of neurogenetics in Gaucher disease. 821 80

Gaucher's disease is a lipidosis caused by deficiency of the enzyme glucocerebrosidase (glucosylceramidase) with secondary accumulation of glucocerebrosides in macrophage lysosomes. Three clinical forms of the disease have been described with autosomal recessive genetic basis. They are caused by many different mutations in glucocerebrosidase gene which have been recently identified. The infantile (type III) and juvenile (type II) forms involve the central nervous system and are very rare. Type I is a non neuronopathic form and is the most common lysosomal storage disease, reaching an incidence of 1 in 2500 births among Ashkenazi jews. Clinical manifestations include splenomegaly and hypersplenism, while bone and lung involvement are less common. Most patients have a mild course and a normal life expectancy, but some others suffer for heavy bone pain that greatly inhabilitate them. A distinctive storage cell is present in bone marrow, but diagnostic confirmation is based upon leucocytes or fibroblasts enzyme assay. Total or partial splenectomy is the treatment of choice for correcting hematological abnormalities. Allogeneic bone marrow transplantation was successfully employed in some cases, while studies on retroviral-mediated gene transfer are undergoing. Promising clinical results were obtained in last two years by chronic infusion of purified macrophage-targeted glucocerebrosidase enzyme. New experience is required in selecting patients for this expensive regimen and establishing duration of therapy.
 ...
PMID:[Update on Gaucher's disease]. 849 69

A 33-year-old man was admitted to our hospital because of thrombocytopenia found on a periodic physical examination. Splenomegaly was recognized Peripheral blood showed WBC 4,510/microliters, Hb 12.5 g/dl, and Plt 40,000/microliters. Increased serum levels of acid phosphatase and angiotensin converting enzyme were observed on laboratory tests. Bone marrow aspirate revealed Gaucher cells. Decreased beta-glucosidase activity was demonstrated in blood leukocytes, cultured blood lymphocytes, and cultured bone marrow fubroblasts from the patient. His glucocerebrosidase genotype was T1448C/C1504T (L444P/R463C). Since neurological examination and skeletal X ray results were normal, Gaucher disease type 1 was diagnosed.
 ...
PMID:[Gaucher disease type 1, incidentally found on a periodic physical examination]. 868 74

A 26-year-old Bedouin with moderate thrombocytopenia and enlarged spleen and liver was diagnosed as having type I Gaucher disease based on the presence of Gaucher cells in the bone marrow biopsy and enzymatic determination of glucocerebrosidase activity. Molecular analysis excluded 10 common mutations in the glucocerebrosidase gene. Homozygosity for the C --> T mutation in nucleotide 259 of the cDNA (1763 genomic) was detected by digestion with restriction enzyme StyI after an amplification of a portion of exon 3 by mismatched primers. This is the first known case of homozygosity for this mutation. The fact that it produces a very mild phenotype, confirms a previous suggestion that 259T can be classified as a "mild" mutation. Association of the 259T mutation with the "Pv 1.1 +" haplotype is consistent with a common origin of the mutated alleles.
 ...
PMID:Type I Gaucher disease due to homozygosity for the 259T mutation in a Bedouin patient. 929 80


1 2 3 4 5 6 Next >>