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)

Numerous enzyme defects-deficiency of pyruvate kinase, phosphofructo-kinase, glocosephosphate isomerase, adenylate kinase, 2,3-diphosphoglycerate mutase and glutathione reductase--in red blood cells have been described to be connected with dyserythropoietic or refractory anemias and panmyelopathies of different origin. These enzyme deficiencies also have been demonstrated in red cells of patients with acute leukemia. Most likely the enzyme deficiencies are acquired and are not important for the origin of anemia or bone marrow insufficiency. Partial derepression of fetal genes, qualitative and quantitative perturbations of genetic expression, and posttranslational variations of the enzyme protein by low molecular factors from plasma, erythrocytes or leukemic cells have been discussed as a reason of enzyme deficiency. The decrease of glutathione reductase deficiency is dependent of FAD deficiency.
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PMID:[Enzyme deficiencies of blood cells in bone marrow insufficiency (author's transl]. 14 42

Blood samples from 722 unrelated patients with anemia and/or reticulocytosis were submitted to our laboratory for red cell enzyme assay during the past 7 years. Among these 722 cases, we found 82 cases of 7 different red cell enzyme deficiencies and 2 of unstable hemoglobin. Abnormalities of pyruvate kinase (PK) were found to cause hemolysis in 55 patients. Although their average PK activity was about 35% of the normal level, 5 showed normal and 2 demonstrated high PK activity. Among 17 patients in whom pyruvate kinase assays or screening tests had been carried out in routine laboratories, the correct diagnoses had been made in only 4. Glucose-6-phosphate dehydrogenase (G6PD) deficiency was found in 15 patients, pyrimidine 5'-nucleotidase deficiency in 5, glucose phosphate isomerase deficiency in 3, adenylate kinase deficiency in 2, phosphoglycerate kinase deficiency in 1, and glutathione synthetase deficiency in 1 patient. Even after we performed a panel of over 20 different red cell enzyme assays, 519 patients still remained undiagnosed.
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PMID:Enzymatic diagnosis in non-spherocytic hemolytic anemia. 335 12

Phosphoglucose isomerase (PGI) and 16 other biochemical genetic markers were studied in an Israeli-Arab family previously described for hereditary deficiency of adenylate kinase (AK) and glucose 6-phosphate dehydrogenase (G6PD). In this inbred family a rare PGI*3 allele was observed in 11 of 32 members tested, indicating an autosomal codominant inheritance. The electrophoretic mobility of this allele is similar to that of the PGI*3 allele found in Indian populations, but unlike the Indian allele, it has a very low specific activity and heat stability. This PGI*3 allele, designated PGI*3 (Israel), seems to be a different unstable mutation and along with AK and G6PD deficiencies seems to be associated with severe anaemia.
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PMID:PGI*3(Israel), a new, unstable allele in the phosphoglucose isomerase system. 347 58

A number of non-glycolytic metabolic abnormalities may occur in erythrocytes without significantly altering cell function or life span. They include deficiencies of adenine or hypoxanthine-guanine phosphoribosyltransferases, adenosine deaminase, nucleoside phosphorylase, and hyperactivity of ribosephosphate pyrophosphokinase. Three principal enzyme defects are causally associated with hemolytic anemia: hyperactive adenosine deaminase and deficiencies of adenylate kinase and pyrimidine nucleotidase. These produce hemolytic syndromes of variable severity ranging from mild or subclinical in the adenosine deaminase defect to severe in adenylate kinase deficiency. Pyrimidine nucleotidase deficiency is much more common and is associated with intermediate degrees of anemia. Acquired nucleotidase deficiency may occur secondary to lead toxicity and produces a syndrome virtually identical to the hereditary deficiency states.
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PMID:Hereditary disorders of erythrocyte enzymes in non-glycolytic metabolic pathways. 718 78

Red cell hemolysis is classically diagnosed by a combination of nonspecific laboratory tests, including serum bilirubin, LDH, and the reticulocyte count. None of these tests alone or in combination has the specificity to reliably ascertain the presence of hemolysis. We have previously demonstrated that erythrocyte adenylate kinase (EAK) is a red cell specific enzyme released from damaged red cells. Its activity can be measured in serum by rapid electrophoresis or immunological methods and correlates linearly with the degree of hemolysis in vitro. We now report on a clinical study comparing EAK levels in patients with and without hemolysis. The clinical diagnosis of hemolysis was established in hospitalized patients with anemia by the combined elevation of the bilirubin, LDH, and reticulocyte count in the absence of liver disease and demonstrable blood loss. The normal range of serum EAK was determined in 30 healthy nonanemic voluntary blood donors and was 0-3.5 Units (mean = 0.5). In 25 patients with hemolytic anemia due to sickle cell disease, hemolytic transfusion reactions, or TTP, the mean EAK level was 62.4 with a range 0-298 Units (P < 0.001 compared to normals). Levels of EAK exceeded the normal range in 24 of 25 patients (96%). In a control group of 44 hospitalized patients with liver disease or myocardial infarction and no clinical evidence of hemolysis, the mean EAK level was 0.12 with a range of 0-3.2 (P = 0.1, NS compared to normals and P < 0.001 compared to patients with hemolysis). None of the control patients had EAK levels that exceeded the normal range. The diagnostic sensitivity of the EAK assay for hemolysis, as calculated according to Baye's algorithm, was 96%, with a specificity and accuracy of 97%. Measurement of serum EAK represents a highly sensitive and specific test for the diagnosis of hemolytic anemia.
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PMID:Diagnosis of the hemolytic state using serum levels of erythrocyte adenylate kinase. 1086 13

We report here 2 patients with chronic nonspherocytic hemolytic anemia (CNSHA) and severe red blood cell (RBC) adenylate kinase (AK) deficiency. One of these patients, a boy of Spanish origin, exhibited a neonatal icterus and splenomegaly and required blood transfusions until the age of 2 years. The other patient was a white, American infant born to parents who were first cousins; he also presented with neonatal icterus and anemia. In neither case was psychomotor impairment observed. The first patient was found to be a compound heterozygote for 2 different missense mutations, 118G>A(Gly40Arg) and 190G>A(Gly64Arg) (cDNA sequence first described by Matsuura et al, 1989). The second patient was homozygous for an in-frame deletion (GAC) from nucleotide (nt) 498 to 500 or nt 501 to 503 of the cDNA sequence, predicting deletion of either aspartic acid (Asp) 140 or 141. The crystal structure of porcine cytosolic AK was used as a molecular model to investigate how these mutations may affect enzyme structure and function.
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PMID:Red cell adenylate kinase deficiency: molecular study of 3 new mutations (118G>A, 190G>A, and GAC deletion) associated with hereditary nonspherocytic hemolytic anemia. 1264 62

We report the hematological, biochemical, and molecular characteristics of a new defective adenylate kinase (AK) variant associated with chronic hemolytic anemia. The propositus was a 3-year-old girl of southern Italian origin with a history of severe anemia and occasional need for blood transfusion. The study of the most important red cell enzymes revealed low AK activity (22% of normal) in the propositus and intermediate values in the parents. The sequence of erythrocyte AK-1 gene showed a new homozygous mutation (delG138) determining a frameshift and a premature stop at codon 91.
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PMID:A new variant of adenylate kinase (delG138) associated with severe hemolytic anemia. 1531 93

Most patients with anemia are diagnosed through clinical phenotype and basic laboratory testing. Nonetheless, in cases of rare congenital anemias, some patients remain undiagnosed despite undergoing an exhaustive workup. Genetic testing is complicated by the large number of genes that are involved in rare anemias, due to similarities in the clinical presentation. We sought to enhance the diagnosis of patients with congenital anemias by using targeted next-generation sequencing. The genetic diagnosis was performed by gene capture followed by next-generation sequencing of 76 genes known to cause anemia syndromes. Genetic diagnosis was achieved in 17 of 21 transfusion-dependent patients and undiagnosed by conventional workup. Four cases were diagnosed with red cell membrane protein defects, four patients were diagnosed with pyruvate kinase deficiency, one case of adenylate kinase deficiency, one case of glucose phosphate isomerase deficiency, one case of hereditary xerocytosis, three cases having combined membrane and enzyme defect, two cases with Diamond-Blackfan anemia (DBA) and 1 with CDA type II with 26 different mutations, of which 21 are novel. Earlier incorporation of this NGS method into the workup of patients with congenital anemia may improve patient care and enable genetic counselling.
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PMID:Study of pathophysiology and molecular characterization of congenital anemia in India using targeted next-generation sequencing approach. 3140 66