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)

A case of liver glycogen storage disease with amylo 1,6-glucosidase deficiency is reported. Enlarged liver was found at birth, and it is now accompanied by splenomegaly, low fasting blood glucose with ketonuria, elevation of transaminase values and glycogen accumulation with connective periportal tissue in liver histological study. In this glucogenosis results of functional tests on carbohidrate metabolism and glycogen enzymatic assay showed a direct relationship between functional and biochemical behaviour of liver cells. Amylo 1,6-glucosidase deficiency is accompanied by absence of glucogenolysis when glucagon is administrated after a long fast, and an increase of blood glucose when glucagon is administrated after food ingestion. Glycolisis tests show blood lactate elevation when some hexose or alanine are administrated; glyconeogenesis tests show blood glucose elevation when hexose, alanine or glycerol are administrated.
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PMID:[Glycogen storage disease by amylo 1,6-glucosidase deficiency (author's transl)]. 693 53

The purpose of this study was to evaluate the efficacy and toxicity of recombinant human granulocyte colony-stimulating factor (rhG-CSF) therapy in patients with neutropenia and/or neutrophil dysfunction secondary to glycogen storage disease (GSD) type 1b. Thirteen patients with neutropenia and/or neutrophil dysfunction secondary to GSD type 1b were treated with rhG-CSF. The effects of therapy on neutrophil numbers and in vitro neutrophil function and on bone marrow cellularity and morphology were studied. The clinical status of the patients and the occurrence of adverse events associated with rhG-CSF use were monitored. Use of rhG-CSF therapy was associated with a significant increase in circulating neutrophil numbers (P <. 01) and an improvement in neutrophil function as assessed in vitro. In addition, rhG-CSF therapy produced a significant increase in marrow cellularity and an increase in myeloid:erythroid (M:E) ratio, indicating stimulation of granulopoeisis. No adverse effects on marrow function were noted; in particular, no myelodysplasia or marrow exhaustion was seen. Use of rhG-CSF therapy was associated with objective and subjective improvements in infection-related morbidity. The therapy was well tolerated, although all patients developed splenomegaly, and 5 patients developed mild hypersplenism that did not require any specific treatment. rhG-CSF therapy is efficacious in the management of neutropenia and neutrophil dysfunction associated with GSD type 1b. Patients on this therapy need to be monitored for hypersplenism. Continued follow-up will be necessary to confirm long-term safety; however, no significant short-term toxicity was noted.
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PMID:Recombinant human granulocyte colony-stimulating factor therapy for patients with neutropenia and/or neutrophil dysfunction secondary to glycogen storage disease type 1b. 1115 11

Mutations in the gene for muscle phosphofructo-1-kinase (PFKM), a key regulatory enzyme of glycolysis, cause Type VII glycogen storage disease (GSDVII). Clinical manifestations of the disease span from the severe infantile form, leading to death during childhood, to the classical form, which presents mainly with exercise intolerance. PFKM deficiency is considered as a skeletal muscle glycogenosis, but the relative contribution of altered glucose metabolism in other tissues to the pathogenesis of the disease is not fully understood. To elucidate this issue, we have generated mice deficient for PFKM (Pfkm(-/-)). Here, we show that Pfkm(-/-) mice had high lethality around weaning and reduced lifespan, because of the metabolic alterations. In skeletal muscle, including respiratory muscles, the lack of PFK activity blocked glycolysis and resulted in considerable glycogen storage and low ATP content. Although erythrocytes of Pfkm(-/-) mice preserved 50% of PFK activity, they showed strong reduction of 2,3-biphosphoglycerate concentrations and hemolysis, which was associated with compensatory reticulocytosis and splenomegaly. As a consequence of these haematological alterations, and of reduced PFK activity in the heart, Pfkm(-/-) mice developed cardiac hypertrophy with age. Taken together, these alterations resulted in muscle hypoxia and hypervascularization, impaired oxidative metabolism, fiber necrosis, and exercise intolerance. These results indicate that, in GSDVII, marked alterations in muscle bioenergetics and erythrocyte metabolism interact to produce a complex systemic disorder. Therefore, GSDVII is not simply a muscle glycogenosis, and Pfkm(-/-) mice constitute a unique model of GSDVII which may be useful for the design and assessment of new therapies.
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PMID:Phosphofructo-1-kinase deficiency leads to a severe cardiac and hematological disorder in addition to skeletal muscle glycogenosis. 1969 89

Glycogen storage disease type I (GSD-I) is a group of autosomal recessive disorders that include types Ia and Ib. GSD-Ib is caused by a deficiency in the glucose-6-phosphate transporter (G6PT) caused by a mutation in the SLC37A4 gene coding for G6PT. Glycogen storage disease is characterized by poor tolerance to fasting, growth retardation and hepatomegaly resulting from accumulation of glycogen and fat in the liver and chronic neutropenia. Herein we describe a 4-month-old Turkish patient with early onset and severe typical clinical features of GSD-1b in which a novel mutation in the SLC37A4 gene was detected. After the bone marrow examination parenteral antibiotic therapy and subcutaneous granulocyte colony-stimulating factor (G-CSF) were started. Due to the severe neutropenia the patient had developed nosocomial sepsis and the dose of G-CSF was increased. After 2 months later from the initial treatment of the G-CSF he developed splenomegaly and urinary complications. Despite maximal therapy he had an extremely poor quality of life and life-threatening complications due to impaired bone marrow function. As the patient required continual hospitalization he was schedule for bone marrow transplantation.
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PMID:Glycogen storage disease type 1b: an early onset severe phenotype associated with a novel mutation (IVS4) in the glucose 6-phosphate translocase (SLC37A4) gene in a Turkish patient. 2580 16

Liver cirrhosis represents a state of end-stage failure that is usually fatal. The condition results in liver dysfunction, recurrent ascites, encephalopathy, renal failure, splenomegaly, bleeding, and a poor quality of life in general. With the current severe shortage of donated organs, the only available treatment in the developing countries remains palliative care. We report a case of congenital metabolic liver cirrhosis due to glycogen storage disease diagnosed at age eight. The patient, a male, received bone marrow derived mononuclear cells (BMMC) at age 16 and again at age 17 with significant improvement of his biochemical liver function tests, ascites build-up, asthenia, splenomegaly and quality of life. Furthermore, liver biopsies showed clear reduction of the inflammation and fibrosis from Ishak score dropped from 3 to 1 paralleling the symptomatic improvement of the patient.
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PMID:A case report of congenital glycogen storage liver cirrhosis treated with bone marrow derived stem cells. 2905 45