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)

Hb Madrid, in which the alanine residue at beta115 (G17) is replaced by proline, results in a moderately severe hemolytic anemia due to the disruption of an alpha helical region and the weakening of an alpha1 beta1 contact (1,2). It was first discovered in a single Spanish patient, by protein structural analysis, whose parents did not carry the abnormality (1). The second observation of Hb Madrid was in an American Black teenager by DNA analysis, who had the family history of chronic hemolytic anemia, but none of family members were available for evaluation (3).
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PMID:Hb Madrid [beta115(G17)Ala-->Pro] in a Korean family with chronic hemolytic anemia. 1087 Aug 84

We describe three mutations of the red-cell anion exchangerband 3 (AE1, SLC4A1) gene associated with distalrenal tubular acidosis (dRTA) in families from Malaysia and Papua NewGuinea: Gly(701)-->Asp (G701D), Ala(858)-->Asp(A858D) and deletion of Val(850) (DeltaV850). The mutationsA858D and DeltaV850 are novel; all three mutations seem to berestricted to South-East Asian populations. South-East Asianovalocytosis (SAO), resulting from the band 3 deletion of residues400-408, occurred in many of the families but did not itselfresult in dRTA. Compound heterozygotes of each of the dRTA mutationswith SAO all had dRTA, evidence of haemolytic anaemia and abnormal red-cell properties. The A858D mutation showed dominant inheritance and therecessive DeltaV850 and G701D mutations showed a pseudo-dominantphenotype when the transport-inactive SAO allele was also present. Red-cell and Xenopus oocyte expression studies showed that theDeltaV850 and A858D mutant proteins have greatly decreased aniontransport when present as compound heterozygotes (DeltaV850/A858D,DeltaV850/SAO or A858D/SAO). Red cells with A858D/SAO had only 3% ofthe SO(4)(2-) efflux of normal cells, thelowest anion transport activity so far reported for human red cells. The results suggest dRTA might arise by a different mechanism for eachmutation. We confirm that the G701D mutant protein has an absoluterequirement for glycophorin A for movement to the cell surface. Wesuggest that the dominant A858D mutant protein is possibly mis-targetedto an inappropriate plasma membrane domain in the renal tubular cell,and that the recessive DeltaV850 mutation might give dRTA because ofits decreased anion transport activity.
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PMID:Band 3 mutations, renal tubular acidosis and South-East Asian ovalocytosis in Malaysia and Papua New Guinea: loss of up to 95% band 3 transport in red cells. 1092 24

Hb Mont Saint-Aignan [beta128(H6)Ala-->Pro] is a mildly unstable variant, associated with hemolytic anemia, marked microcytosis and increased alpha/beta biosynthetic ratio (1.55 versus 1.1 +/- 0.1 in the control). The abnormal chain was isolated by selective precipitation with isopropanol and the structural modification determined by protein chemistry methods (reversed phase high performance liquid chromatography and mass spectrometry). Possible mechanisms underlying the beta(+)-thalassemia-like expression of this variant are discussed.
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PMID:Hb Mont Saint Aignan [beta128(H6)Ala-->Pro]: a new unstable variant leading to chronic microcytic anemia. 1130 Mar 50

NZB mice spontaneously develop autoimmune haemolytic anaemia (AIHA) due to a T helper-dependent autoantibody response against the erythrocyte anion channel protein, Band 3. Here, we characterize the recognition of the Band 3 sequence 861-874, which carries the dominant, I-E(d)-restricted T cell epitope. The ability of N and C-terminal truncated versions of peptide 861-874 to elicit NZB splenic T-cell proliferation indicated that the core epitope spans residues 862-870. Next, a set of alanine substitution analogues was tested to determine which residues functioned either as MHC anchor or TCR contact residues. A combination of proliferation and MHC:peptide binding assays identified residues 862(L), 864(V), 865(L), and 869(K) as I-E(d) anchor residues, and 868(V) as the only TCR contact residue. The ability of the wild-type sequence 861-874 to compete with a high affinity reference peptide for binding to I-E(d) indicates that the escape of pathogenic NZB T cells from purging of the autoreactive repertoire cannot be attributed to ineffective presentation of peptide 861-874 by its restricting element. It will now be possible to design altered peptide ligands of Band 3 861-874, in order to further dissect the mechanisms responsible for the maintenance and loss of T cell tolerance to RBC autoantigens, and to modulate the immune response in AIHA.
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PMID:Characterization of the dominant autoreactive T-cell epitope in spontaneous autoimmune haemolytic anaemia of the NZB mouse. 1190 47

As many as one-third of mutations in a gene result in the corresponding enzyme having an increased Michaelis constant, or K(m), (decreased binding affinity) for a coenzyme, resulting in a lower rate of reaction. About 50 human genetic dis-eases due to defective enzymes can be remedied or ameliorated by the administration of high doses of the vitamin component of the corresponding coenzyme, which at least partially restores enzymatic activity. Several single-nucleotide polymorphisms, in which the variant amino acid reduces coenzyme binding and thus enzymatic activity, are likely to be remediable by raising cellular concentrations of the cofactor through high-dose vitamin therapy. Some examples include the alanine-to-valine substitution at codon 222 (Ala222-->Val) [DNA: C-to-T substitution at nucleo-tide 677 (677C-->T)] in methylenetetrahydrofolate reductase (NADPH) and the cofactor FAD (in relation to cardiovascular disease, migraines, and rages), the Pro187-->Ser (DNA: 609C-->T) mutation in NAD(P):quinone oxidoreductase 1 [NAD(P)H dehy-drogenase (quinone)] and FAD (in relation to cancer), the Ala44-->Gly (DNA: 131C-->G) mutation in glucose-6-phosphate 1-dehydrogenase and NADP (in relation to favism and hemolytic anemia), and the Glu487-->Lys mutation (present in one-half of Asians) in aldehyde dehydrogenase (NAD + ) and NAD (in relation to alcohol intolerance, Alzheimer disease, and cancer).
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PMID:High-dose vitamin therapy stimulates variant enzymes with decreased coenzyme binding affinity (increased K(m)): relevance to genetic disease and polymorphisms. 1191 49

We report the case of a 3-year-old Japanese boy with phosphoglycerate kinase 1 (PGK1) deficiency (Online Mendelian Inheritance in Man entry 311800). The patient had anaemia and jaundice at birth, necessitating exchange transfusions for 2 d. After one red blood cell transfusion at age 2 months, his Hb level was 8-9 g/dl, his reticulocyte counts were 300-500 x 109/l, and his total bilirubin level was 25.65-42.75 micro mol/l. The patient suffered two episodes of respiratory infection-associated haemolytic crisis and rhabdomyolysis during early infancy. At age 3.0 years, his developmental milestones (developmental quotients measured using the Tsumori-Inage methods) score was 49% (normal 74-131%), and his height was below average by -2.0 standard deviations. The diagnosis of PGK1 deficiency was made based on his remarkably low (< 10% of normal) erythrocyte PGK enzyme activity level and the identification of a novel missense (1060G-->C) PGK1 gene mutation. This mutation results in the Ala-353Pro amino acid substitution, which has been designated PGK Kyoto. The patient developed the full clinical symptoms of PGK1 deficiency including haemolytic anaemia, myopathy, central nervous system disorder and growth retardation, which is unusual.
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PMID:A novel missense mutation (1060G --> C) in the phosphoglycerate kinase gene in a Japanese boy with chronic haemolytic anaemia, developmental delay and rhabdomyolysis. 1295 73

We report a 13-year-old girl who presented with hepatic failure and hemolytic anemia. Laboratory findings showed a normal serum copper level (104 microg/dl), high urinary copper level (2370 microg/dl), and low serum ceruloplasmin level (14.3 microg/dl). Slit-lamp examination revealed Kayser-Fleischer rings on her cornea, and she was diagnosed with Wilson's disease. Plasma exchange and continuous hemodiafiltration relieved the serious condition, after that laparoscopic examination was performed. Administration of D-penicillamine and restriction of dietary copper (<1 mg/day) were started, leading to a normalized serum alanine amino transferase (ALT) level. After 3 years, she again underwent laparoscopic examination, and the laparoscopic and histological findings of her liver were obviously improved. Management of the copper level can reverse severe liver fibrosis in Wilson's disease.
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PMID:D-Penicillamine improved laparoscopic and histological findings of the liver in a patient with Wilson's disease: 3-year follow-up after diagnosis of Coombs-negative hemolytic anemia of Wilson's disease. 1600

We describe a new hyper-unstable beta chain variant (codons 137-139, -6 bp) in a 2-year-old Bulgarian boy. The abnormal hemoglobin (Hb) is associated with severe hemolytic anemia as a consequence of its hyper instability. The child was admitted to the Pediatric Clinic (Faculty of Medicine, Stara Zagora, Bulgaria) at the age of 2 months. Because of anemia (Hb 6.9 g/dL) and high serum iron level (58 microM/L) the child was transfused. However, a month later his Hb level had dropped to 7.5 g/dL, and since then he has been on a regular monthly blood transfusion regimen. Hemoglobin analysis of a blood sample collected 2 months after the last transfusion at the age of 2 years, revealed no abnormalities except for the presence of inclusion bodies after incubation of peripheral blood with brilliant cresyl blue. Sequencing of the beta-globin gene revealed heterozygosity for a 6 bp deletion (-TGGCTA) at codons 137 [the second and third base pair (bp)], 138 and 139 (the first bp), forming a new codon at position 137 (GAT). This event eliminates three amino acids (Val-Ala-Asn) and introduces a new residue (Asp). It creates a new restriction site for HphI. The parents and his dizygotic twin brother had no history of hemolysis. The paternity of the child was confirmed by DNA analysis.
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PMID:Hb Stara Zagora: a new hyper-unstable hemoglobin causing severe hemolytic anemia. 1637 Apr 84

We report a new hemoglobin (Hb) variant, Hb Marineo [beta70(E14)Ala --> Val], found in three generations of a family from West Sicily. The mutation is due to a GCC --> GTC substitution at codon 70 of the beta-globin gene. To date, three mutations at codon 70 of the beta-globin gene have been described, presenting with hemolytic anemia. In our case, no anemia or other alteration of hematological indices were found. Cation exchange high performance liquid chromatography (HPLC) showed a peak in the P2 window (VARIANT I), while a peak was detected by VARIANT II HPLC in the P3 window. Reversed phase HPLC analysis showed an abnormal chain amounting to about 40% of the total beta chains.
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PMID:Hb Marineo [beta70(E14)Ala-->Val]: a silent hemoglobin variant with a mutation within the heme pocket. 1679 37

Dominantly inherited beta-thalassemia (thal) or "inclusion body beta-thalassemias" are heterogeneous at the molecular level and are due to mutations at or near the beta-globin gene locus. Many of these involve mutations of exon 3 of the beta-globin gene. They include frameshifts, premature chain termination (nonsense) mutations, and complex rearrangements that lead to the synthesis of truncated or elongated and highly unstable beta-globin gene products. The resulting beta chain variants are very unstable, and in many cases, the products of the dominantly inherited beta-thal are not detectable. Hematological and clinical observations made in several families with comparable forms of beta-thal and with certain highly unstable hemoglobin (Hb) variants, have indicated a striking overlap; many subjects with detectable unstable Hb variants and with a dominant type of beta-thal without a detectable abnormal Hb, have similar phenotypes. Here, a review of dominantly inherited beta-thal is given, and new examples of hyperunstable Hbs (Hb Stara Zagora and Hb Jambol) are presented. The first example is a hyperunstable variant named Hb Stara Zagora that was found in a 2-year-old Bulgarian boy. The abnormal Hb is associated with severe hemolytic anemia as a consequence of its hyper instability. The anemia was noticed at the age of 2 months and since then he has been on a regular monthly blood transfusion regimen. Hemoglobin analysis revealed no abnormalities, except the presence of inclusion bodies. Sequencing of the beta-globin gene revealed a heterozygosity for a 6 bp deletion (-TGGCTA) at codons 137 (the second and third bp), 138 and 139 (the first bp), thus forming a new codon at position 139 (GAT). This event eliminates three amino acids (Val-Ala-Asn) and introduces a new residue (Asp). It creates a new restriction site for HphI. The parents and his twin brother had no history of hemolysis. The paternity of the child was confirmed by DNA analysis. The second example is a new hyperunstable variant named Hb Jambol, found as a de novo mutation in a 2-year-old Bulgarian girl with severe hemolytic anemia. The mutation was detected through RNA/DNA analysis. It represents a complex genomic rearrangement involving an insertion of 23 nucleotides (nts) after IVS-II-535, a deletion of 310 nts extending from IVS-II-550 to the first nt of codon 108, and an insertion of 28 nts at the deletion junctions (derived from inverted sequence between nts +3707 and +3734 3' to the beta-globin gene termination codon). At the protein level, this mutation leads to a deletion of four amino acid residues (Leu-Leu-Glu-Asn) at positions 105, 106, 107 and 108, and an insertion of nine residues (Val-Pro-Ser-Val-Thr-Leu-Phe-Phe-Asp) at the same location, creating an abnormal elongated beta chain of 151 amino acid residues. The parents had no history of hemolysis. The paternity of the child was confirmed by DNA analysis.
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PMID:Dominantly Inherited beta-Thalassemia. 1748 3


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