Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A previous study revealed that DQ-2511, a new gastroprokinetic drug, induced hemolytic anemia together with increased Heinz body formation, preceded by a marked decrease in erythrocyte reduced glutathione (GSH) content, after 2 weeks of dosing onward in dogs. In this study, the effect of DQ-2511 on erythrocytes in the early period of dosing, in comparison with that of beta-acetylphenylhydrazine (APHZ), was investigated to confirm the difference between this drug and APHZ in the mechanism of increased Heinz body formation. DQ-2511 and APHZ were administered orally to beagle dogs for 1 week at dose levels of 600 and 4 mg/ kg, respectively. Dogs receiving APHZ showed anemia after dosing for 7 days, together with an increase in methemoglobin and Heinz body formation after 3 days of dosing. In contrast, blood GSH, glutathione reductase, and gamma-glutamylcysteine synthetase were only slightly decreased after dosing for 7 days. In dogs treated with DQ-2511, erythrocyte GSH began to decrease after 1 day of treatment and was about 25% of the control value after 7 days; however, no changes were seen in blood glutathione reductase, GSH peroxidase, or gamma-glutamylcysteine synthetase level. Hepatic GSH was decreased slightly. In another experiment, SD rats were administered DQ-2511 and APHZ orally for 1 week at dose levels of 1600 and 15 mg/kg, respectively. Rats receiving DQ-2511 showed no anemia or any changes in erythrocyte GSH and Heinz body formation. In contrast, rats treated with APHZ showed a marked anemia and increases in Heinz body formation and erythrocyte GSH. These results demonstrate that DQ-2511 causes a marked decrease in GSH in dogs, resulting in Heinz body anemia, whereas APHZ induces Heinz body formation after a significant increase in methemoglobin, and suggest that impairment of the GSH redox cycle and synthetases of GSH are not involved in the decreased GSH after DQ-2511 treatment. This difference in effects on GSH content may indicate the existence of a species difference in the anemia induced by DQ-2511.
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PMID:A possible mechanism of heinz body hemolytic anemia induced by DQ-2511, a new gastroprokinetic drug, in dogs. 892 30

A previously undescribed mutation of hereditary gamma-glutamylcysteine synthetase (GCS) deficiency was found in a 5 year old boy of Moroccan origin. He presented with chronic haemolytic anaemia, delayed psychomotor development and progressive motor sensitive neuropathy of lower extremities. The parents were third degree relatives. The activity of glycolytic enzymes were found to be normal in the propositus, his parents and a sister, but and a complete lack of GSH was found in the propositus. Accordingly, the measurement of de novo GSH synthetic enzymes was undertaken, and severe GCS deficiency was found in the propositus. Both parents and his sister presented GCS activity ranging from 69% to 90% of normal. GCS gene sequencing showed that the propositus was homozygous for a 1241C>T mutation in exon 11 and both parents and his sister were heterozygous. This mutation predicts a Pro414Leu amino acid substitution. Even though the homology between GCS and crystallographically solved, functionally related proteins is not very high, a three-dimensional model of GCS was derived using Modeller Software. GCS deficiency is a very rare autosomal recessive disorder reported so far in only 8 unrelated probands with severe haemolytic anaemia. In only 3 of these was the anaemia associated with severe neurological dysfunction. We report here the fourth case of GCS deficiency presenting neuropathy, giving further support to the eventual relationship between this enzymopathy and neurological damage.
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PMID:Chronic non-spherocytic hemolytic anemia associated with severe neurological disease due to gamma-glutamylcysteine synthetase deficiency in a patient of Moroccan origin. 1802 85

Glutathione (gamma-glutamylcysteinylglycine) has diverse functions including free radicals scavenging and modulating many critical cellular processes. Glutathione is synthesized by the consecutive action of the enzymes glutamate-cysteine ligase (GCL) and glutathione synthetase. GCL is composed of a catalytic subunit encoded by the GCLC gene and a regulatory subunit encoded by the GCLM gene. GCL deficiency due to homozygous mutations in GCLC has been reported in 6 individuals from 4 independent families. All presented with hemolytic anemia and 4 had additional neurological manifestations including cognitive impairment, neuropathy, ataxia, and myopathy. In this report, we present additional 6 children from 2 independent consanguineous families with GCL deficiency. All the children presented with neonatal hemolytic anemia. Beyond the neonatal period, they did not have jaundice or hemolysis, but continued to have mild anemia. They all had normal development and neurological examination. The affected children from the first family had the homozygous mutation c.1772G>A (p.S591N) and the second family had the homozygous mutation c.514T>A (p.S172T) in GCLC. GCL deficiency can have a mild non-neurological phenotype or a more severe phenotype with neurological manifestations. GCL deficiency can be an underdiagnosed cause of hemolytic anemia, thus awareness may aid in early diagnosis, appropriate genetic counseling, and management.
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PMID:Clinical and molecular characterization of 6 children with glutamate-cysteine ligase deficiency causing hemolytic anemia. 2857 79