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)

A 16-month-old girl of Spanish origin with chronic hemolytic anemia and severe neuromuscular disease was found to have markedly reduced triosephosphate isomerase (TPI) activity in her erythrocytes, leukocytes, and plateletes. Both parents and some other family members had moderately reduced erythrocyte TPI activity in accordance with the autosomal recessive mode of inheritance in this enzymopathy. Latex ingestion and latex-stimulated histochemical NBT reduction by the patient's granulocytes were normal. Zymosan-stimulated superoxide radical (O-.2) formation, not previously studied in TPI-deficient granulocytes, was also within normal limits. Starchgel electrophoresis of TPI in both erythrocytes and leukocytes of the proposita and her parents was normal. Molecular studies of deficient TPI showed a normal kinetic pattern with markedly reduced heat instability. Immunologic studies demonstrated no cross reacting material in proposita leukocytes and a normal molecular specific activity. These studies suggest that molecular instability might cause both enzymatic and antigenic degradation of the TPI molecule and, therefore, TPI deficiency in our patient.
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PMID:Triosephosphate isomerase deficiency with hemolytic anemia and severe neuromuscular disease: familial and biochemical studies of a case found in Spain. 66 2

A 19-year-old girl fell ill with a high temperature and cervical lymphadenopathy. The detection of heterophile antibodies as well as Epstein-Barr-virus-specific antibodies confirmed the diagnosis of infectious mononucleosis. In the course of the infection, the patient developed severe hemolytic anemia with her hemoglobin falling from 14 to 8 g/dl. High-dose corticosteroid therapy did not stop hemolysis; this could only be achieved by seven plasmapheresis sessions. Antibodies against triosephosphate isomerase (TPI) and the blood group marker 'i' were found in the patient's serum. Anti-i cold agglutinins were not active at 37 degrees C, whereas antibodies against TPI caused increased 51Cr release from marked patient's erythrocytes in vitro. Plasmapheresis removed the autoantibodies effectively and stopped the hemolysis. After 8 weeks, the patient gradually recovered.
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PMID:Successful plasmapheresis in corticosteroid-resistant hemolysis in infectious mononucleosis: role of autoantibodies against triosephosphate isomerase. 146 97

A new triosephosphate isomerase (TPI) variant is described in an 8-year-old Turkish girl suffering from chronic haemolytic anaemia, myopathy and developmental retardation since early infancy. The enzyme activity profile revealed a generalized deficiency in erythrocytes, granulocytes, mononuclear blood cells, skeletal muscle tissue and cerebrospinal fluid. The concentration of enzyme substrate dihydroxyacetone phosphate was distinctly elevated. Biochemical examination showed accelerated enzyme deamidation, the first step in the normal catabolism of TPI during aging of the erythrocyte. The specific activity of the variant TPI, determined by antibody titration, was reduced to 61% of normal. Its heat stability was markedly decreased. Muscle biopsy and neuropsychological testing further clarified the pathogenesis of the disorder. A prevalent alteration of mitochondria similar to that seen in mitochondrial myopathy and an elevated amount of intracellular glycogen were found. The patient's retarded intellectual development was mainly due to impaired visual perception and sensory-motor co-ordination in addition to a lack of syllogistic reasoning. The findings indicate that the low TPI activity leads to a metabolic block of the glycolytic pathway and hence to a generalized impairment of cellular energy supply.
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PMID:Triosephosphate isomerase deficiency: haemolytic anaemia, myopathy with altered mitochondria and mental retardation due to a new variant with accelerated enzyme catabolism and diminished specific activity. 195 37

During the relatively recent period in which normal genes for most red cell enzymes have been isolated, the techniques of molecular biology have been applied to the studies of erythroenzymopathy. Single nucleotide substitutions have been identified in aldolase, triosephosphate isomerase, glucose 6-phosphate dehydrogenase, and adenylate kinase variants by the cloning and nucleotide sequence of the patients' genes. Up to now, all of the enzyme-deficient variants which have been investigated have been caused by point mutations. An exception is a hemolytic anemia secondary to increased adenosine deaminase (ADA) activity. Red cell ADA activity increases on the order of a hundred-fold in affected individuals. The basic abnormality appears to result from overproduction of structurally normal enzyme due to abnormal transcriptional or translational efficiency.
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PMID:Recent progress in the molecular genetic analysis of erythroenzymopathy. 216 22

Morphological changes are shown in the muscle biopsy specimens of an 8-year-old girl who suffered from a triosephosphate isomerase (TPI) deficiency, resulting in a chronic, nonspherocytic, hemolytic anemia, mental retardation and neuromuscular impairment. The newly introduced enzyme histochemical reaction for TPI demonstrated a total lack of histochemically detectable enzyme activity, whereas biochemical analysis of muscle tissue revealed less than 10% of the normal enzyme activity. Electron microscopy showed a degenerative myopathy with an increase in the amount of intracellular glycogen. Additionally, mitochondrial changes within the muscle fibers were observed to be similar to those in mitochondrial myopathies. The disturbed balance between glycerin-aldehyde phosphate and dihydroxyacetone phosphate, due to the deficiency of the TPI enzyme, is interpreted as the biochemical background of an impaired electron transport across the mitochondrial membrane, resulting in the coexistence of an impaired glycolytic pathway and an impaired mitochondrial metabolism of muscle cells.
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PMID:Myopathy with altered mitochondria due to a triosephosphate isomerase (TPI) deficiency. 233 91

Since the discovery of glucose-6-phosphate dehydrogenase (G6PD) deficiency and pyruvate kinase deficiency, erythroenzymopathies associated with hereditary hemolytic anemia have been extensively investigated. Kinetic and electrophoretic studies have shown that most erythroenzymopathies are caused by the production of a mutant enzyme. Single amino acid substitutions have been determined in G6PD and phosphoglycerate kinase variants by studies of the enzyme. Except for these two enzymes, it has been difficult to purify and to characterize the patient's enzyme because of the low protein contents in red blood cells. Recent advance in recombinant DNA technology has made possible the isolation of normal genomic DNA or cDNA for several enzymes. These results permit us to study the molecular basis of erythroenzymopathies at the nucleotide level. Single base substitutions have been identified in aldolase, triosephosphate isomerase, G6PD and adenylate kinase variants by the cloning and nucleotide sequence of the patients' genes. To date, all of the enzyme-deficient variants which have been investigated are caused by point mutations. An exception is a hemolytic anemia secondary to increased adenosine deaminase (ADA) activity. Red cell ADA activity increases on the order of a hundred-fold in affected individuals. The basic abnormality appears to result from overproduction of structurally normal enzyme due to abnormal translational efficiency.
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PMID:[Pathophysiology and laboratory tests of hemolytic anemia: with special reference to erythroenzymopathies]. 269 73

Triose-phosphate isomerase (TPI; D-glyceraldehyde-3-phosphate ketol-isomerase, EC 5.3.1.1) deficiency is a recessive disorder that results in hemolytic anemia and neuromuscular dysfunction. To determine the molecular basis of this disorder, a TPI allele from two unrelated patients homozygous for TPI deficiency was compared with an allele from a normal individual. Each disease-associated sequence harbors a G X C----C X G transversion in the codon for amino acid-104 and specifies a structurally altered protein in which a glutamate residue is replaced by an aspartate residue. The importance of glutamate-104 to enzyme structure and function is implicated by its conservation in the TPI protein of all species that have been characterized to date. The glutamate-to-aspartate substitution results in a thermolabile enzyme as demonstrated by assays of TPI activity in cultured fibroblasts of each patient and cultured Chinese hamster ovary (CHO) cells that were stably transformed with the mutant alleles. Although this substitution conserves the overall charge of amino acid-104, the x-ray crystal structure of chicken TPI indicates that the loss of a side-chain methylene group (-CH2CH2COO- ---- -CH2COO-) is sufficient to disrupt the counterbalancing of charges that normally exists within a hydrophobic pocket of the native enzyme.
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PMID:Human triose-phosphate isomerase deficiency: a single amino acid substitution results in a thermolabile enzyme. 287 30

Two siblings with hemolytic anemia caused by triosephosphate isomerase deficiency developed a progressive neurological syndrome featuring dystonic movements, tremor, pyramidal tract signs, and evidence of spinal motor neuron involvement. Intelligence was unaffected. The findings in these patients and in 14 previously published cases indicate that neurological manifestations are an integral part of the disorder and suggest that specific structures in the basal ganglia, brainstem, and spinal cord bear the brunt of the pathological process, which does not affect the cerebral cortex.
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PMID:Neurological findings in triosephosphate isomerase deficiency. 400 68

2 new cases of triosephosphate isomerase (TPI) deficiency associated with severe haemolytic anaemia in 2 unrelated Italian families are described. Only 1 case was extensively investigated. TPI deficiency was detectable in erythrocytes, leucocytes, platelets and plasma. The mutant enzyme showed normal Km for GAP and increased Km for DHAP, with an higher than normal equilibrium constant, decreased thermostability, and abnormal electrophoretic pattern due to the lack of the fastest moving component. The immunological characterization revealed a lower than normal inactivation by specific antiserum, while the double immunodiffusion pattern and the precipitin curve were normal. Lymphocyte, granulocyte and platelet functions were impaired.
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PMID:Triosephosphate isomerase deficiency: 2 new cases. 401 21

Seven new homozygous cases of hereditary triosephosphate isomerase (TPI) deficiency have been detected in five unrelated families. Two of the families originate in France, the others from Algeria, Yugoslavia, and Morocco. Only the parents coming from Algeria and Morocco were first cousins. In the other parents no evidence of consanguinity was found. All seven patients exhibited the same symptoms, i.e. hemolytic anemia appearing very early after birth associated with progressive neuromuscular symptoms. Expression of the deficiency is heterogeneous; this had previously been pointed out in the previously reported cases of TPI deficiency. Red cell TPI activity was 3 to 4% of the normal mean in the patients and 50 to 60% in the parents. The latter did not exhibit any clinical symptoms. The levels of red cell glycolytic intermediates and the characteristics of the mutated TPI could be studied in four of the patients only. Substantial increases of red cell dihydroxyacetone phosphate and of fructose 1,6-diphosphate, normal Km of TPI for glyceraldehyde phosphate, and thermoinstability of the enzyme were found. In addition the electrophoretic pattern showed no significant modification of the mobility of the TPI bands, but abnormal decreased staining of the two more anodal bands.
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PMID:Hereditary triose phosphate isomerase deficiency: seven new homozygous cases. 406 96


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