1/77. priapism caused by glucose phosphate isomerase deficiency.A case of congenital non-spherocytic hemolytic anemia of unknown etiology is described. The patient had priapism and further hematologic evaluation revealed a glucose phosphate isomerase deficiency. This is the first report of priapism secondary to a defect of erythrocyte metabolism.- - - - - - - - - - ranking = 1keywords = hemolytic (Clic here for more details about this article) |
2/77. Two new glucose 6-phosphate dehydrogenase variants associated with congenital nonspherocytic hemolytic anemia found in japan: GD(-) Tokushima and GD(-) tokyo.Two new variants of glucose 6-phosphate dehydrogenase (G6PD) deficiency associated with chronic nonspherocytic hemolytic anemia were discovered in japan. Gd(-) Tokushima was found in a 17-years-old male whose erythrocytes contained 4.4% of normal enzyme activity. Partially purified enzyme revealed a main band of normal electrophoretic mobility with additional two minor bands of different mobility; normal Km G6P, and Km nadp five-to sixfold higher than normal; normal utilization of 2-deoxy-G6P, galactose-6P, and deamino-nadp; marked thermal instability; a normal pH curve; and normal Ki NADPH. The hemolytic anemia was moderate to severe. Gd(-) tokyo was characterized from a 15-year-old male who had chronic nonspherocytic hemolytic anemia of mild degree. The erythrocytes contained 3% of normal enzyme activity, and partially purified enzyme revealed slow electrophoretic mobility (90% of normal for both a tris-hydrochloride buffer system and a tris-EDTA-borate buffer system, and 70% of normal for a phosphate buffer system); normal Km G6P and Km nadp; normal utilization of 2-deoxy-G6P, galactose-6P, and deamino-nadp; greatly increased thermal instability; a normal pH curve; and normal Ki NADPH. These two variants are clearly different from hitherto described G6PD variants, including the Japanese variants Gd(-) Heian and Gd(-) Kyoto. The mothers of both Gd(-) Tokushima and Gd(-) Tokoyo were found to be heterozygote by an ascorbate-cyanide test.- - - - - - - - - - ranking = 7keywords = hemolytic (Clic here for more details about this article) |
3/77. Several mutations including two novel mutations of the glucose-6-phosphate dehydrogenase gene in Polish G6PD deficient subjects with chronic nonspherocytic hemolytic anemia, acute hemolytic anemia, and favism.dna sequencing revealed seven different glucose-6-phosphate dehydrogenase (G6PD) mutations in G6PD deficient subjects from 10 Polish families. Among them we found two novel mutations: 679C-->T (G6PD Radlowo, class 2) and a 1006A-->G (G6PD Torun, class 1). Variant G6PD Radlowo was characterized biochemically. Both novel mutations were analyzed using a model of the tertiary structure of the human enzyme. The main chain of G6PD Torun is different from the wild-type G6PD. The remaining mutations identified by us in deficient Polish patients were: 542A-->T (G6PD Malaga), 1160G-->A (G6PD Beverly Hills), 1178G-->A (G6PD Nashville), 1192G-->A (G6PD Puerto Limon), and 1246G-->A (G6PD tokyo). Variant tokyo was found in four families. In one of them favism was the first clinical sign of G6PD deficiency and chronic nonspherocytic hemolytic anemia (CNSHA) was diagnosed later. Variants G6PD Nashville and G6PD Puerto Limon were accompanied by the silent mutation 1311C-->T of the G6PD gene.- - - - - - - - - - ranking = 9keywords = hemolytic (Clic here for more details about this article) |
4/77. glucose-6-phosphate dehydrogenase aveiro: a de novo mutation associated with chronic nonspherocytic hemolytic anemia.glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common X-linked enzyme abnormality. The clinical phenotype is variable but often predictable from the molecular lesion. Class I variants (the most severe forms of the disease) cluster within exon 10, in a region that, at the protein level, is believed to be involved in dimerization. Here we describe a de novo mutation (C269Y) of a new class I variant (G6PD Aveiro) that maps to exon 8. Mutant and normal alleles were found in both hematopoietic and buccal cells, indicating the presence of mosaicism. The available model of the protein predicts that this lesion lies in proximity to the dimer interface of the molecule. A possible mechanism to explain the severity of the defect is proposed. (Blood. 2000;95:1499-1501)- - - - - - - - - - ranking = 4keywords = hemolytic (Clic here for more details about this article) |
5/77. Triosephosphate isomerase deficiency with elevated sweat chloride test: report of a case.A 15-month-old girl with severe hemolytic anemia and progressive respiratory failure is presented. She was well until the age of six months when she developed a pulmonary infection. During the next six months, she had frequent respiratory infections and her paleness became evident. At the age of 12 months, she was observed to have easy fatigability and muscle weakness, and she received her first blood transfusion. She was referred to our hospital at the age of 15 months. The physical examination revealed a malnourished girl with hypotonia, nystagmus, generalized muscle weakness and severe breathing difficulty requiring ventilatory support The hemoglobin (Hb) was 9.7 g/dl; hematocrit (Hct) 29%, mean corpuscular volume (MCV) 101 fl and reticulocyte count 15%. Peripheral blood smear revealed macrocytosis and stomatocytosis (30% of the red cells) and polychromasia. sweat chloride test was 90 and 94 mEq/L on two separate occasions. The serum vitamin e level was 0.26 mg/dl (N: 0.44-0.68). She was found to be heterozygous for factor v Leiden mutation. Although malnutrition, low serum vitamin e and elevated sweat chloride test were suggestive of cystic fibrosis, this diagnosis failed to account for all the findings in the patient. A search for a red cell enzyme deficiency revealed that the red cell triosephosphate isomerase (TPI) activity was low. dna analysis showed the 315 G-C (105 Glu-Asp) TPI mutation, thus confirming the diagnosis of TPI deficiency.- - - - - - - - - - ranking = 1keywords = hemolytic (Clic here for more details about this article) |
6/77. Cardiac dysfunction because of secondary hemochromatosis caused by congenital non-spherocytic hemolytic anemia.Most patients diagnosed with secondary hemochromatosis have had repeated blood transfusions. Cardiac failure accounts for approximately one-third of the deaths associated with hemochromatosis. liver dysfunction or hormonal disorders such as diabetes generally precede cardiac failure. A 23-year-old woman with hemochromatosis had, despite significant left ventricular dysfunction, liver function within the normal range on biochemical evaluation. She was treated for congestive heart failure and given desferoxamine intravenously. She did not have primary hemochromatosis, and had not received multiple blood transfusions or iron supplement. As a child the patient had been diagnosed with congenital non-spherocytic hemolytic anemia not requiring transfusion; thus, this is a unique case of secondary hemochromatosis.- - - - - - - - - - ranking = 5keywords = hemolytic (Clic here for more details about this article) |
7/77. Direct antiglobulin test negative, non spherocytic autoimmune haemolytic anaemia.We report a case of direct antiglobulin test (DAT) negative warm autoimmune haemolytic anaemia (AIHA). At initial presentation our patient had compensated haemolysis and was DAT positive for complement only. Severe haemolytic anaemia developed some years later with a negative DAT. spherocytes were not a feature of the blood film and osmotic fragility studies were negative. Immune mediated haemolysis was confirmed by fluorescent activated cell sorter (FACS) analysis using antihuman IgG immunoglobulin. Response to immunosuppression was transient but a good response was achieved following splenectomy. Repeat FACS analysis post splenectomy demonstrated a marked rise in IgG coated red cells. Techniques used in establishing the diagnosis and possible mechanisms for this presentation are discussed.- - - - - - - - - - ranking = 0.52132923051701keywords = anaemia (Clic here for more details about this article) |
8/77. Recurrent thromboembolic disease following splenectomy for pyruvate kinase deficiency.We report a case of recurrent thromboembolic disease and chronic pulmonary hypertension in an adult patient with pyruvate kinase deficiency who underwent splenectomy as a child. thromboembolism has been reported as a complication following splenectomy for various hereditary chronic hemolytic anemias. To our knowledge, this association has not been described in patients specifically with pyruvate kinase deficiency. Our patient presented at age 37 with recurrent pulmonary emboli, 36 years after splenectomy for severe hemolytic anemia. work-up for other hypercoagulable states was negative. The mechanism for hypercoagulability in this condition is unclear but may involve a quantitative or qualitative change in disrupted thrombogenic red blood cell membranes that would normally be removed by the spleen. Clinicians should have a high index of suspicion for thrombotic events in these patients, as early diagnosis and treatment can reduce morbidity and mortality, and chronic anticoagulation may help prevent the sequelae of repeated thromboembolic events.- - - - - - - - - - ranking = 2keywords = hemolytic (Clic here for more details about this article) |
9/77. HK Utrecht: missense mutation in the active site of human hexokinase associated with hexokinase deficiency and severe nonspherocytic hemolytic anemia.hexokinase deficiency is a rare autosomal recessive disease with a clinical phenotype of severe hemolysis. We report a novel homozygous missense mutation in exon 15 (c.2039C>G, HK [hexokinase] Utrecht) of HK1, the gene that encodes red blood cell-specific hexokinase-R, in a patient previously diagnosed with hexokinase deficiency. The Thr680Ser substitution predicted by this mutation affects a highly conserved residue in the enzyme's active site that interacts with phosphate moieties of adenosine diphosphate, adenosine triphosphate (ATP), and inhibitor glucose-6-phosphate. We correlated the molecular data to the severe clinical phenotype of the patient by means of altered enzymatic properties of partially purified hexokinase from the patient, notably with respect to Mg(2 )-ATP binding. These kinetic properties contradict those obtained from a recombinant mutant brain hexokinase-I with the same Thr680Ser substitution. This contradiction thereby stresses the valuable contribution of studying patients with hexokinase deficiency to achieve a better understanding of hexokinase's key role in glycolysis.- - - - - - - - - - ranking = 4keywords = hemolytic (Clic here for more details about this article) |
10/77. G-6-PD Long Prairie: a new glucose-6-phosphate dehydrogenase mutant exhibiting normal sensitivity to inhibition by NADPH and accompanied by nonspherocytic hemolytic anemia.The enzymatic properties of a new glucose-6-phosphate dehydrogenase (G-6-PD) variant (G-6-PD Long Prairie) were studied in a white patient with chronic nonspherocytic hemolysis. The red cells were found to have 2.3%-7.7% normal enzymatic activity. The mutant enzyme exhibited marked heat instability, an increased pH optimum, a moderately decreased Km for G-6-P, and increased utilization of 2-deoxyglucose-6-phosphate and deamino nadp. The Km for nadp and Ki for NADPH were both normal. G-6-PD Long Prairie is an interesting new G-6-PD variant that demonstrates that chronic hemolysis can be associated with modestly decreased G-6-PD activity despite normal sensitivity to inhibition by NADPH. Although increased sensitivity to inhibition by NADPH has been postulated to decrease intracellular enzyme activity, resulting in enhanced susceptibility to hemolysis in certain G-6-PD variants with only moderately decreased enzymatic activity, an alternative mechanism of hemolysis, possibly enzyme thermolability, exists in G-6-PD Long Prairie.- - - - - - - - - - ranking = 4keywords = hemolytic (Clic here for more details about this article) |
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