Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0002878 (hemolytic anemia)
7,530 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Paroxysmal nocturnal hemoglobinuria (PNH) is a hematopoietic stem cell (HSC) disorder in which an acquired somatic mutation of the X-linked PIGA gene results in a deficiency in GPI-anchored surface proteins. Clinically, PNH is dominated by a chronic hemolytic anemia, often associated with recurrent nocturnal exacerbations, neutropenia, thrombocytopenia, and thrombotic tendency. Allogenic bone marrow transplantation is the only potentially curative treatment for severe forms of PNH but is associated with a high treatment-related morbidity and mortality. HSC gene therapy could provide a new therapeutic option, especially when an HLA-matched donor is not available. To develop an efficient gene transfer approach, we have designed a new SIN lentiviral vector (TEPW) that contains the PIGA cDNA driven by the human elongation factor 1 alpha promoter, the central DNA flap of HIV-1, and the WPRE cassette. TEPW transduction led to a complete surface expression of the GPI anchor and CD59 in PIGA-deficient cell lines without any selection procedure. Moreover, efficient gene transfer was achieved in bone marrow and mobilized peripheral blood CD34(+) cells derived from two patients with severe PNH disease. This expression was stable during erythroid, myeloid, and megakaryocytic liquid culture differentiation. CD59 surface cell expression was fully restored during 5 weeks of long-term culture.
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PMID:A SIN lentiviral vector containing PIGA cDNA allows long-term phenotypic correction of CD34+-derived cells from patients with paroxysmal nocturnal hemoglobinuria. 1266 26

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the commonest red cell enzymopathy in humans and has an X-linked inheritance. It has been reported from India more than 30 years ago and the prevalence varies from 0-27% in different caste, ethnic and linguistic groups. The major clinical manifestations are drug induced hemolytic anemia, neonatal jaundice and chronic non-spherocytic hemolytic anemia. Individuals with G6PD deficiency have a selective advantage against falciparum malaria. Thirteen biochemically characterized variants have been reported from India. At the molecular level, G6PD Mediterranean is the most common deficient variant in the caste groups whereas, G6PD Orissa is more prevalent among the tribal of India. The third common variant seen in India is G6PD Kerala-Kalyan.
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PMID:Glucose-6-phosphate dehydrogenase deficiency in India. 1522 63

We retrospectively reviewed the clinical and immunological features as well as the outcome of children with a diagnosis of primary hypogammaglobulinemia, who were treated at the National Taiwan University Hospital between 1984 and 2001. A total of 33 patients were enrolled: seventeen patients with common variable immunodeficiency (CVID), six patients with selective immunoglobulin deficiencies (one subclass IgA and five IgG), four patients with severe combined immunodeficiency (SCID), three patients with transient hypogammaglobulinemia of infancy (THI) and three patients with X-linked (Bruton) agammaglobulinemia (XLA). In addition to recurrent sinopulmonary infections and prolonged fever, allergic diseases are noted in 76% of CVID patients and 100% of patients with selective immunodeficiencies. Immunoglobulin levels were extremely low in XLA and decreased in CVID patients. Three SCID patients had decreased mean absolute lymphocyte counts of 290/mm3. Long-term complications included bronchiectasis in 2 XLA patients, 2 CVID patients and 1 patient with selective immunodeficiency; short stature in one of each XLA, SCID, and CVID patients respectively; poor school performance in 2 SCID patients and 1 XLA patient; and hemolytic anemia in 1 CVID patient. We concluded that in addition to a thorough physical examination, a family history of early death from infection and past history of neonatal hyperbilirubinemia, are crucial in evaluating a patient with suspicious primary hypogammaglobulinemia. The associated symptoms of primary hypogammaglobulinemia, such as recurrent sinopulmonary infections, prolonged fever and allergic diseases, are also diagnostic clues. In the treatment of hypogammaglobulinemia, early and regular high doses of Intravenous immunoglobulin (IVIG) supplement may avoid the development or decrease the severity of bronchiectasis.
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PMID:Immunological and clinical features of pediatric patients with primary hypogammaglobulinemia in Taiwan. 1536 55

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked red blood cell enzymopathy common in malaria endemic areas. Individuals affected by this disease show a wide variety of clinical signs of acute hemolytic anemia. Mutations of the G6PD gene in the Malay population with G6PD deficiency in Kelantan, a state in North East Malaysia were studied. Ninety-three individuals with G6PD deficiency were subjected to mutation analysis of the G6PD gene using polymerase chain reaction based techniques of multiplex PCR. Of the ninety-three DNA samples studied, molecular defects were identified in 80 cases (86%). Variants were heterogeneous - 28.7% were found to have a G to A nucleotide change at nucleotide 871 of the G6PD gene (G871A), corresponding to G6PD Viangchan. The other major mutations were G6PD Mediterranean, G6PD Vanua Lava, G6PD Coimbra, G6PD Kaiping, G6PD Orissa, G6PD Mahidol, G6PD Canton and G6PD Chatham. These results showed that there are heterogeneous mutations of the G6PD gene associated with G6PD deficiency and that G6PD Viangchan and G6PD Mediterranean account for the main variants in G6PD deficiency among the Malay population in Malaysia.
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PMID:G6PD Viangchan and G6PD Mediterranean are the main variants in G6PD deficiency in the Malay population of Malaysia. 1590 17

Glucose 6-phosphate dehydrogenase is a highly polymorphic enzyme encoded by a human X-linked gene (Xq2.8). This enzyme catalyses the first step of pentose phosphate pathway, that converts glucose 6-phosphate to 6-phosphogluconate with production of NADPH2. G6PD deficiency is the most common human metabolic inborn error affecting more than 400 million people world wide. The main clinical manifestations are acute hemolytic anemia and jaundice, triggered by infection or ingestion of Fava beans or oxidative drugs. A predominant variant of G6PD named Mediterranean is often associated with favism. This has been evident in several countries including Northern coastal provinces of Iran. Other current variants are Chatham and Cosenza. Molecular identification of the most prevalent mutations in G6PD gene was carried out in 71 males and females with G6PD deficiency. They were from Iranian Northern province of Golestan. DNA was extracted from blood samples and analyzed for known G6PD mutation by PCR and restriction fragment length polymorphisms (RFLP) technique. Adapting this method, revealed that Mediterranean mutation at nt 563(C-->T) is predominant in the area (69%) and 26.7% of patients have Chatham mutation at nt 1003(G-->A). Findings indicate a higher prevalence of these mutations, in Golestan compared to Mazandaran (66.2% Mediterranean and 19% Chatham mutation) and Gilan (86.4% Mediterranean and 9.71% Chatham mutations). Cosenza mutation at nt 1376(G-->C), by PCR-RFLP technique was not found among other 3 samples (4.3%). The similarity of these results with mutations in Italy indicates probable existence of a common ancestral origin in the observed populations.
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PMID:Molecular identification of mutations in G6PD gene in patients with favism in Iran. 1595 46

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hematological disorder characterized by the clonal expansion and differentiation of a multi-potent hematopoietic stem cell carrying a somatic mutation in the X-linked PIG-A gene. As a consequence of this mutation, glycosylphosphatidylinositol (GPI)-anchored proteins are lacking on the surface of blood cells derived from the mutated stem cell. This may result clinically in hemolytic anemia and a tendency for venous thrombosis and serious infection. Bone marrow failure is a frequently observed phenomenon associated with PNH. Reliable diagnosis of PNH is currently best achieved by flow cytometric analysis of GPI-anchored proteins on peripheral blood cells. Both the clinically relevant size of the PNH clone and type of GPI deficiency (complete or partial) can be reproducibly determined by this method. Most patients will benefit from supportive measures, albeit that allogeneic hematopoietic stem cell transplantation is currently considered the only potentially curative therapy. The development of a new therapeutic monoclonal antibody that reduces intravascular hemolysis and progress in diagnostic flow cytometry using a new GPI-specific marker may provide further benefit for PNH patients in the future.
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PMID:[Paroxysmal nocturnal hemoglobinuria--consequences of a missing anchor]. 1645 Jul 36

Phosphoglycerate kinase (PGK) deficiency is a rare X-linked disease that is characterised by mild to severe haemolytic anaemia, rhabdomyolysis, and variable defects in the central nervous system. In a white American family, two sons presented with haemolytic anaemia, seizures, and developmental delay. The diagnosis of PGK deficiency was made based on the remarkably low (<5% of normal) erythrocyte PGK enzyme activity level and the identification of a missense (c. 491A --> T) PGK1 gene mutation. This mutation results in an Asp164Val amino acid substitution, which has previously been designated PGK-Amiens and PGK-New York. The two new patients have the full clinical syndrome of PGK deficiency including haemolytic anaemia, developmental delay and seizures, and in the proband, hemiplegic migraines, retinal dystrophy and muscle fatigue. The PGK-Amiens/New York mutation had previously been found in a French patient and also in a large Chinese-Australian kindred, indicating that either the c. 91A --> T mutation is a recurrent mutation or that there is shared ancestry between the patients that have been identified so far with the mutation. Haplotype analysis of the c. 91A --> T mutation indicated that this was a recurrent mutation.
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PMID:The identification of a recurrent phosphoglycerate kinase mutation associated with chronic haemolytic anaemia and neurological dysfunction in a family from USA. 1674 Jan 38

Paroxysmal nocturnal hemoglobinuria (PNH) is an uncommon intravascular hemolytic anemia that results from the clonal expansion of hematopoietic stem cells harboring somatic mutations in an X-linked gene, termed PIG-A. PIG-A mutations block glycosylphosphatidylinositol (GPI) anchor biosynthesis, resulting in a deficiency or absence of all GPI-anchored proteins on the cell surface. CD55 and CD59 are GPI-anchored complement regulatory proteins. Their absence on PNH red cells is responsible for the complement-mediated intravascular hemolysis. Intravascular hemolysis leads to release of free hemoglobin, which contributes to many of the clinical manifestations of PNH including fatigue, pain, esophageal spasm, erectile dysfunction and possibly thrombosis. Interestingly, rare PIG-A mutations can be found in virtually all healthy control subjects, leading to speculation that PIG-A mutations in hematopoietic stem cells are common benign events. However, negative selection of PIG-A mutant colony-forming cells with proaerolysin, a toxin that targets GPI-anchored proteins, reveals that most of these mutations are not derived from stem cells. Recently, a humanized monoclonal antibody directed against the terminal complement protein C5 has been shown to reduce hemolysis and greatly improve symptoms and quality of life for PNH patients.
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PMID:New insights into paroxysmal nocturnal hemoglobinuria. 1712 35

Phosphoglycerate kinase (PGK) deficiency is one of the relatively uncommon causes of hereditary non-spherocytic haemolytic anaemia (HNSHA). The gene encoding the erythrocyte enzyme PGK1, is X-linked. Mutations of this gene may cause chronic haemolysis with or without mental retardation and they may cause myopathies, often with episodes of myoglobinuria, or a combination of these clinical manifestations. Twenty-six families have been described and in 20 of these the mutations are known. The reason for different clinical manifestations of mutations of the same gene remains unknown.
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PMID:PGK deficiency. 1722 95

Deficiency of glucose-6-phosphate dehydrogenase is a very common X-linked genetic disorder though most deficient people are asymptomatic. A number of different G6PD variants have reached polymorphic frequencies in different parts of the world due to the relative protection they confer against malaria infection. People, usually males, with deficient alleles are susceptible to neonatal jaundice, and acute hemolytic anemia, usually during infection, after treatment with certain drugs or after eating fava beans. Very rarely de novo mutations can arise causing the more severe condition of chronic nonspherocytic hemolytic anemia. Altogether 160 different mutations have been described. The majority of mutations cause red cell enzyme deficiency by decreasing enzyme stability. The polymorphic mutations affect amino acid residues throughout the enzyme and decrease the stability of the enzyme in the red cell, possibly by disturbing protein folding. The severe mutations mostly affect residues at the dimer interface or those that interact with a structural NADP molecule that stabilizes the enzyme.
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PMID:G6PD deficiency: the genotype-phenotype association. 1761 Oct 6


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