1/76. Hemoglobin Moabit: alpha 86 (F7) Leu leads to Arg: a new unstable abnormal hemoglobin.A new alpha chain abnormal hemoglobin variant was found in a Turkish patient with a mild Heinz body hemolytic anemia and splenomegaly. The substitution alpha 86 Leu leads to Arg, which is next to the heme binding proximal histidine, is responsible for a marked instability of the molecule. The oxygen affinity of the erythrocytes was found to be slightly decreased.- - - - - - - - - - ranking = 1keywords = oxygen (Clic here for more details about this article) |
2/76. Identification of an erythrocyte pyruvate kinase variant in a family from Latium with non-spherocytic congenital haemolytic anaemia.Erythrocyte PK deficiency was detected in a family from Latium in italy. This PK variant is characterized by normal or increased activity immediately after blood collection, instability to storage, to heat and to urea. Only in the propositus the mutant enzyme exhibited an increased Michaelis constant for PEP, slightly increased inhibition by ATP and an altered optimum pH value. The kinetic anomaly was only partially corrected by activation with F-1, 6-DP and by addition of 2-ME. From these results it can be concluded that in the family observed two distinct erythrocyte PK alterations were demonstrable: instability in the propositus and his father; low affinity for PEP and altered optimum pH value only in the propositus.- - - - - - - - - - ranking = 136.05744290462keywords = deficiency (Clic here for more details about this article) |
3/76. Hereditary non-spherocytic haemolytic anaemia due to red blood cell glutathione synthetase deficiency in four unrelated patients from spain: clinical and molecular studies.In four unrelated patients with chronic haemolysis and markedly reduced red blood cell (RBC) glutathione (49.5%, 12.6%, 11.5% and 15% of the normal concentration respectively), a severe glutathione synthetase (GSH-S, EC 6.3.2.3) deficiency was found. One case exhibited a neonatal haemolytic anaemia associated with oxoprolinuria, but without neurological manifestations. The family study revealed GSH-S activity in both parents to be around half the normal level, a finding consistent with the presumed autosomal recessive mode of inheritance of this enzymopathy. Two cases exhibited a well-compensated haemolytic syndrome without anaemia or splenomegaly at steady state. One of these cases was diagnosed after an episode of acute haemolytic anaemia after fava bean ingestion. The remaining patient suffered from moderate to severe chronic non-spherocytic haemolytic anaemia and splenomegaly, and required occasional blood transfusion for a haemolytic crisis associated with drug ingestion. In this patient, the anaemia was corrected by splenectomy. In addition to GSH-S, a panel of 16 other RBC enzyme activities was also studied in all the patients. hexokinase, aldolase, glucose-6-phosphate dehydrogenase and pyruvate kinase activities all increased; these increases were to be expected, given the rise in the number of circulating reticulocytes. In two patients, the incubation of RBCs with hydrogen peroxide revealed an enhanced production of malonyldialdehyde. dna analysis showed a homozygous state for 656 A-->G mutation in patients 2 and 3. The GSH-S gene of patient 1, studied elsewhere, revealed an 808 T-->C. The GSH-S gene of patient 4 was not available for study. The present study demonstrates that GSH-S deficiency is also present in spain and further supports the molecular and clinical heterogeneity of this enzymopathy- - - - - - - - - - ranking = 816.34465742771keywords = deficiency (Clic here for more details about this article) |
4/76. A new glucose-6-phosphate dehydrogenase variant G6PD Sugao (826C-->T) exhibiting chronic hemolytic anemia with episodes of hemolytic crisis immediately after birth.A case of glucose-6-phosphate dehydrogenase (G6PD) deficiency associated with chronic hemolysis with episodes of hemolytic crisis immediately after birth is reported. The propositus was a 1-month-old Japanese male infant. Molecular analysis of the G6PD gene revealed a novel missense mutation (826C-->4T) in exon 8 predicting a single amino acid substitution, Pro276Ser. The mother was confirmed to be heterozygous for this mutation. We designated this novel class 1 variant as G6PD Sugao. Pro276 is a phylogenetically conserved residue that may play a significant role in dimer formation.- - - - - - - - - - ranking = 136.05744290462keywords = deficiency (Clic here for more details about this article) |
5/76. Glucosephosphate isomerase deficiency in a Dutch family.A mentally retarded girl with severe hemolytic anemia due to glucosephosphate isomerase deficiency is described. The deficiency was detected in erythrocytes, leukocytes, thrombocytes, liver and muscle tissues. Besides the glucosephosphate isomerase deficiency, a glutathione instability of unknown origin was found in the erythrocytes of the propositus.- - - - - - - - - - ranking = 952.40210033233keywords = deficiency (Clic here for more details about this article) |
6/76. Severe jaundice in a patient with a previously undescribed glucose-6-phosphate dehydrogenase (G6PD) mutation and Gilbert syndrome.A patient with chronic hemolytic anemia and G6PD deficiency was noted to be severely jaundiced and to have a high serum ferritin level. Analysis of his dna revealed only heterozygosity for the c.187 C-->G (H63D) mutation of HFE, but showed that he was homozygous for the UDP glucuronosyltransferase promoter mutation of Gilbert's disease and that he had a previously undescribed mutation of G6PD, c.832 T-->C (Ser278Pro). The new variant was named G6PD La Jolla.- - - - - - - - - - ranking = 136.05744290462keywords = deficiency (Clic here for more details about this article) |
7/76. Chronic haemolytic anaemia and glucose-6 phosphate dehydrogenase deficiency. Case report and review of the literature.Deficiency in glucose-6-phosphate dehydrogenase (G6PD) is the most common enzymopathy, and more than 125 different mutations causing G6PD deficiency have been identified. Chronic haemolytic anaemia (CHA) associated with G6PD deficiency is rare, but there is a cluster of mutations causing CHA between amino acids 361-428 which are encoded by exon 10 of the G6PD gene. This region is involved in the dimer formation of the active G6PD enzyme and therefore plays an important role for enzyme stability and activity. Here, we report a 17-year-old patient with CHA, who carries a rare G --> A mutation at nucleotide 1160 which causes an R387H amino acid substitution. We review the reports of the seven previously described patients with this mutation, concluding that G6PD deficiency should be considered as a rare differential diagnosis of chronic haemolytic, non-spherocytic anaemia.- - - - - - - - - - ranking = 952.40210033233keywords = deficiency (Clic here for more details about this article) |
8/76. A family with red cell pyrimidine 5'-nucleotidase deficiency.Congenital hemolytic anemia associated with pyrimidine 5'-nucleotidase deficiency is reported in two siblings. Both have had moderate chronic hemolytic anemia, splenomegaly, and jaundice since early infancy. The peripheral blood smear is characterized by striking red cell basophilic stippling. As this feature has been found in all previously reported cases, it should be the clue to the diagnosis.- - - - - - - - - - ranking = 680.28721452309keywords = deficiency (Clic here for more details about this article) |
9/76. A novel missense mutation (1060G --> C) in the phosphoglycerate kinase gene in a Japanese boy with chronic haemolytic anaemia, developmental delay and rhabdomyolysis.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.- - - - - - - - - - ranking = 408.17232871386keywords = deficiency (Clic here for more details about this article) |
10/76. Hemolytic anemia and severe rhabdomyolysis caused by compound heterozygous mutations of the gene for erythrocyte/muscle isozyme of aldolase, ALDOA(Arg303X/Cys338Tyr).Aldolase (E.C. 4.1.2.13), a homotetrameric protein encoded by the ALDOA gene, converts fructose-1,6-bisphosphate to dihydroxyacetone phosphate and glyceraldehyde-3-phosphate. Three isozymes are encoded by distinct genes. The sole aldolase present in red blood cells and skeletal muscle is the A isozyme. We report here the case of a girl of Sicilian descent with aldolase A deficiency. Clinical manifestations included transfusion-dependent anemia until splenectomy at age 3 and increasing muscle weakness, with death at age 4 associated with rhabdomyolysis and hyperkalemia. sequence analysis of the ALDOA coding regions revealed 2 novel heterozygous ALDOA mutations in conserved regions of the protein. The paternal allele encoded a nonsense mutation, Arg303X, in the enzyme-active site. The maternal allele encoded a missense mutation, Cys338Tyr, predicted to cause enzyme instability. This is the most severely affected patient reported to date and only the second with both rhabdomyolysis and hemolysis.- - - - - - - - - - ranking = 136.05744290462keywords = deficiency (Clic here for more details about this article) |
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