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)

We have investigated two unrelated patients with congenital haemolytic anaemia in both of whom we found a combination of hereditary spherocytosis (HS) and glucose-6-phosphate dehydrogenase (G6PD) deficiency. Segregation of the two defects was documented in both families, who had different molecular abnormalities for both HS and G6PD deficiency. In one family the propositus had a reduced level of spectrin and G6PD Seattle (282Asp-->His). In the other family the propositus had a band 3 abnormality and was heterozygous for G6PD Mediterranean (188Ser-->Phe). From a comparison of clinical and haematological findings in family members with either or both abnormalities we conclude that in one case the two defects exhibited a synergistic effect, resulting in a severe chronic haemolytic anaemia; whereas in the other the association was simply additive.
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PMID:Glucose 6-phosphate dehydrogenase deficiency and red cell membrane defects: additive or synergistic interaction in producing chronic haemolytic anaemia. 794 39

More than 80 variants of glucose-6-phosphate dehydrogenase (G6PD) are associated with chronic nonspherocytic haemolytic anaemia (CNSHA); however, the molecular basis of this association is not fully understood. We have used the polymerase chain reaction and nucleotide sequence analysis to characterize a new G6PD variant, which we designate as G6PD Bari, in a G6PD-deficient boy affected by CNSHA. A single mutation leading to an amino-acid substitution was detected in the G6PD coding region, viz. a C->T transition at position 1187 predicting leucine at residue 396 in the enzyme; proline is invariably present in evolutionary distant G6PD molecules at this position. Inheritance in the patient's family was demonstrated by the polymerase chain reaction followed by diagnostic restriction enzyme analysis. The C->T transition responsible for G6PD Bari maps close to several other mutations previously identified in G6PD variants associated with CNSHA.
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PMID:A novel single-base mutation in the glucose 6-phosphate dehydrogenase gene is associated with chronic non-spherocytic haemolytic anaemia. 795 95

Volatile nitrites are illegally marketed compounds that have been inhaled by persons who believe that they cause sexual arousal. These substances have been associated with significant hemolysis of red blood cells in patients with decreased or normal glucose-6-phosphate dehydrogenase levels because such nitrites act as cell-membrane oxidants. We report herein a case of hemolysis in a patient with an underlying glucose-6-phosphate dehydrogenase deficiency associated with the use of volatile nitrites, and we also review the literature of volatile nitrite-induced hemolytic anemia.
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PMID:Rush hemolysis. A 'bite-cell' hemolytic anemia associated with volatile liquid nitrite use. 808 34

In a 81-year-old woman, who for many years had been treated with iron and vitamin B12 injections because of a 'tendency to anaemia', congenital haemolytic anaemia on the basis of glucose-6-phosphate dehydrogenase (G6PD) deficiency was diagnosed. The iron and vitamin medication was discontinued and after a blood transfusion because of signs of heart failure, the patient could leave the hospital in good condition. After instruction with regard to provocative factors, like eating of broad beans, no more haemolytic events occurred. Of her children and grandchildren, 2 sons and 1 granddaughter were G6PD deficient.
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PMID:[Glucose-6-phosphate dehydrogenase deficiency in an 81-year-old]. 809 Feb 51

Chronic nonspherocytic hemolytic anemia has been observed in a recently described glucose-6-phosphate dehydrogenase (G6PD) variant, G6PDWayne. The mechanical properties of these erythrocytes and other G6PD variants were examined. The deformability of G6PD-deficient erythrocytes was normal, as determined by osmotic scan ektacytometry, and was not significantly affected by hemolytic crisis. In the common varieties of G6PD deficiency, the mechanical stability of the red blood cell (RBC) membrane was greater than normal, but G6PDWayne membranes were abnormally susceptible to shear-induced fragmentation. There was no evidence for a concurrent genetic defect in spectrin, because self-association constants and tryptic digests were normal. The fragility of G6PDWayne membranes appeared to be a consequence of oxidative damage to membrane thiol groups associated with a low glutathione (GSH) level in these RBCs. Associations among GSH level, thiol oxidation, and membrane instability were also found when a larger group of G6PD-deficient RBCs were examined. In normal erythrocytes, 1-chloro-2,4-dinitrobenzene was used to reduce GSH levels by 50%. Membrane thiol oxidation and membrane fragility both increased when these cells were kept at 4 degrees C for 3 to 5 days. Our findings suggest that chronic depletion of GSH leads to the destabilization of membrane skeleton through oxidation of membrane protein thiols.
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PMID:Oxidant damage to erythrocyte membrane in glucose-6-phosphate dehydrogenase deficiency: correlation with in vivo reduced glutathione concentration and membrane protein oxidation. 811 Oct 51

In the course of molecular studies on Japanese glucose-6-phosphate dehydrogenase (G6PD) variants using single-strand conformation polymorphisms (SSCP) analysis, we found an unusual class 1 G6PD variant that had nucleotide deletion in exon 9. The patient showed chronic nonspherocytic hemolytic anemia associated with frequent episodes of severe hemolytic attack. The hemolysate exhibited no measurable activity. Although the partially purified enzyme had detectable activity, we could not perform kinetic studies because of its extreme instability. Nucleotide sequencing showed a unique 24 bp deletion at nucleotide 953-976 that predicts an eight amino acid deletion of TKGYLDDP at residue 319-326. While this is one of the most drastic structural alterations found in G6PD variants, the region with the amino acid deletion was distant from both the G6P and NADP+ binding sites and was located in a domain with low sequence homology among species. The comparatively low functional importance of the deleted region may have saved the patient from lethal tissue dysfunction.
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PMID:G6PD Nara: a new class 1 glucose-6-phosphate dehydrogenase variant with an eight amino acid deletion. 824 97

Standard treatment of P. ovale and P. vivax malaria is 1500 mg of chloroquine base given over three days followed by 15 mg of primaquine base daily for 14 days. At the Department of Infectious Diseases, Rigshospitalet, Copenhagen an increasing number of cases of relative by primaquine-resistant malaria have been observed. The side effects of primaquine are mainly gastrointestinal. Primaquine may also cause serious toxic side effects, including methaemoglobin formation and haemolytic anaemia, especially in individuals with erythrocyte glucose-6-phosphate dehydrogenase (G-6-PD) deficiency. We present six patients who developed relapses of P. vivax after taking standard doses of primaquine. When increasing primaquine dosage, patients must be informed about the possibility of more severe side effects.
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PMID:[Recurrence problems with preventive primaquine treatment in patients with malaria]. 827 93

A previously healthy 17-year-old Greek boy suddenly developed jaundice of sclerae and skin. In addition, physical examination revealed a pale appearance. He also reported feeling tired and weak. The haemoglobin level was 9.6 g/dl, lactate dehydrogenase activity 335 U/l, bilirubin concentration 3.2 mg/dl (direct bilirubin 0.7 mg/dl, indirect bilirubin 2.5 mg/dl), haptoglobin concentration 48.8 mg/dl. As haemolytic anaemia was assumed, direct questioning elicited the fact that the patient had, for the first time in his life, eaten 300 g of broad beans (Vicia faba) on each of two days, namely 3 and 2 days before the appearance of jaundice. Absence of glucose-6-phosphate dehydrogenase activity in the red blood corpuscles confirmed the diagnosis of favism. On symptomatic treatment both the enzyme activities and the bilirubin level fell to normal within one week, and the haemoglobin level was 15.7 g/dl after 4 weeks.
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PMID:[Broad beans as a cause of acute hemolytic anemia]. 851 17

X-chromosome inactivation in mammals is regarded as an essentially random process, but the resulting somatic-cell mosaicism creates the opportunity for cell selection. In most people with red-blood-cell glucose-6-phosphate dehydrogenase (G6PD) deficiency, the enzyme-deficient phenotype is only moderately expressed in nucleated cells. However, in a small subset of hemizygous males who suffer from chronic nonspherocytic hemolytic anemia, the underlying mutations (designated class I) cause more-severe G6PD deficiency, and this might provide an opportunity for selection in heterozygous females during development. In order to test this possibility we have analyzed four heterozygotes for class I G6PD mutations: two with G6PD Portici (1178G-->A) and two with G6PD Bari (1187C-->T). We found that in fractionated blood cell types (including erythroid, myeloid, and lymphoid cell lineages) there was a significant excess of G6PD-normal cells. The significant concordance that we have observed in the degree of imbalance in the different blood-cell lineages indicates that a selective mechanism is likely to operate at the level of pluripotent blood stem cells. Thus, it appears that severe G6PD deficiency affects adversely the proliferation or the survival of nucleated blood cells and that this phenotypic characteristic is critical during hematopoiesis.
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PMID:Somatic-cell selection is a major determinant of the blood-cell phenotype in heterozygotes for glucose-6-phosphate dehydrogenase mutations causing severe enzyme deficiency. 880 5

Recent progress in the molecular analysis of red cell enzymopathies showed over 160 mutations in the 10 distinct genes which were essential in red cell metabolisms. In addition, since three-dimensional structure of several enzymes including pyruvate kinase (PK) and glucose-6-phosphate dehydrogenase (G6PD) have been elucidated from X-ray crystallographic studies, the effect of amino acid substitutions on enzyme activity became predictable in some extent. On the contrary, the mechanism of hemolysis remains still unclear. To clarify the pathophysiology of red cell enzymopathies, establishment of an animal model have been long awaited. Recently we discovered the novel mice model of PK deficiency. The mutant mice with splenomegaly and nonspherocytic hemolytic anemia in an inbred colony of the CBA strain were enzymatically diagnosed as PK deficiency. A homozygous missense mutation was identified in the red cell (R)-type PKcDNA sequence of the mutant, and it caused a single amino acid substitution near the substrate binding site of PK. The erythroid-progenitor cell number increased in spleen of the mutant mice to a level approximately 66 times higher than in normal CBA mice, suggesting that compensatory extramedullary erythropoiesis in the spleen of the mutant mice might partly compensate the anemia. The mutant mice will be useful as an experimental model for understanding the pathophysiology of this disorder.
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PMID:[Molecular basis and pathophysiology of red cell enzymopathies]. 889 May 66


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