Biomedical subjects
Publications and source records attributed to E M Kimura.
Hemoglobin (Hb) Indianapolis [beta112 (G14) Cys-->Arg] is a rare and slightly unstable beta-globin variant. All carriers described to date were clinically normal with only mild reticulocytosis. We report here a case of a Brazilian patient in whom hemolytic anemia and acute renal failure were probably caused by the presence of this variant.
We report here a new frameshift mutation in exon 3 of the beta-globin gene, a single nucleotide deletion (-C) in between codons 140/141 (GCC/CTG-->GCC/TG), found in an 8-year-old Argentinean girl with clinical picture of thalassemia intermedia. It leads to a beta-chain that is elongated to 156 amino acids [(141)Trp-Pro-Thr-Ser-Ile-Thr-Lys-Leu-Ala-Phe-Leu-Leu-Ser-Asn-Phe-(156)Tyr-COOH]. The resulting hemoglobin, which we named Hb Florida, was not detected in peripheral blood; however, erythroid hyperplasia and dyserythropoiesis with large inclusion bodies on methyl violet staining were observed in bone marrow, suggesting that this is a hyperunstable variant producing a dominant beta-thalassemia phenotype, since the other beta-allele was completely normal.
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We report a case in which the interaction of heterozygosis for both the 0-IVS-II-1 (G->A) mutation and the alpha alpha alpha anti-3,7 allele was the probable cause for the clinical occurrence of thalassemia intermedia. The propositus, a 6-year-old Caucasian Brazilian boy of Portuguese descent, showed a moderately severe chronic anemia in spite of having the -thalassemia trait. Investigation of the alpha-globin gene status revealed heterozygosis for alpha-gene triplication (alpha alpha alpha / alpha alpha). The patient's father, also presenting mild microcytic and hypochromic anemia, had the same alpha and genotypes as his son, while the mother, not related to the father and hematologically normal, was also a carrier of the alpha alpha alpha anti-3,7 allele. The present case emphasizes the need for considering the possibility of alpha-gene triplication in -thalassemia heterozygotes who display an unexpected severe phenotype. The -thalassemia mutation found here is being described for the first time in Brazil.
A patient with Hb H disease resulting from the association of the - alpha 3.7 rightward deletion with the rare (alpha alpha)MM deletion, which removes the entire alpha-major regulatory element (MRE), is reported. This is the first description of an alpha-thalassemic mutation resulting from deletion of the locus-controlling sequences in the South-American population.
In order to determine the contribution of alpha-thalassemia to microcytosis and hypochromia, 339 adult outpatients seen at Unicamp University Hospital (with the exception of the Clinical Hematology outpatient clinics), who showed normal hemoglobin (Hb) levels and reduced mean corpuscular volume and mean corpuscular hemoglobin, were analyzed. Ninety-eight were Blacks (28.9%) and 241 were Caucasians (71.1%). In all cases, Hb A2 and F levels were either normal or low. The most common deletional and nondeletional forms of alpha-thalassemia [-alpha3.7, -alpha4.2, --MED, -(alpha)20.5, alphaHphIalpha, alphaNcoIalpha, alphaalphaNcoI and alphaTSAUDI] were investigated by PCR and restriction enzyme analyses. A total of 169 individuals (49.9%) presented alpha-thalassemia: 145 (42.8%) were heterozygous for the -alpha3.7 deletion (-alpha3.7/alphaalpha) and 18 (5.3%) homozygous (-alpha3.7/-alpha3.7), 5 (1.5%) were heterozygous for the nondeletional form alphaHphIalpha (alphaHphIalpha/alphaalpha), and 1 (0.3%) was a --MED carrier (--MED/alphaalpha). Among the Blacks, 56 (57.1%) showed the -alpha3.7/alphaalpha genotype, whereas 12 (12.2%) were -alpha3.7/-alpha3.7 and 1 (1.0%) was an alphaHphIalpha carrier; among the Caucasians, 89 (36.9%) were -alpha3.7/alphaalpha, 6 (2.5%) had the -alpha3.7/-alpha3.7 genotype, 4 (1.7%) presented the nondeletional form (alphaHphIalpha/alphaalpha), and 1 (0.4%) was a --MED carrier. These results demonstrate that alpha-thalassemia, mainly through the -alpha3.7 deletion, is an important cause of microcytosis and hypochromia in individuals without anemia. These data are of clinical relevance since these hematological alterations are often interpreted as indicators of iron deficiency.
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Seven unrelated patients with hemoglobin (Hb) H disease and 27 individuals with alpha-chain structural alterations were studied to identify the alpha-globin gene mutations present in the population of Southeast Brazil. The -alpha3.7, --MED and -(alpha)20.5 deletions were investigated by PCR, whereas non-deletional alpha-thalassemia (alphaHphalpha, alphaNcoIalpha, alphaalphaNcoI, alphaIcalpha and alphaTSaudialpha) was screened with restriction enzymes and by nested PCR. Structural alterations were identified by direct DNA sequencing. Of the seven patients with Hb H disease, all of Italian descent, two had the -(alpha)20.5/-alpha3.7 genotype, one had the --MED/-alpha3.7 genotype, one had the --MED/alphaHphalpha genotype and three showed interaction of the -alpha3.7 deletion with an unusual, unidentified form of non-deletional alpha-thalassemia [-alpha3.7/(alphaalpha)T]. Among the 27 patients with structural alterations, 15 (of Italian descent) had Hb Hasharon (alpha47Asp-->His) associated with the -alpha3.7 deletion, 4 (of Italian descent) were heterozygous for Hb J-Rovigo (alpha53Ala-->Asp), 4 (3 Blacks and 1 Caucasian) were heterozygous for Hb Stanleyville-II (alpha78Asn-->Lys) associated with the alpha+-thalassemia, 1 (Black) was heterozygous for Hb G-Pest (alpha74Asp-->Asn), 1 (Caucasian) was heterozygous for Hb Kurosaki (alpha7Lys-->Glu), 1 (Caucasian) was heterozygous for Hb Westmead (alpha122His-->Gln), and 1 (Caucasian) was the carrier of a novel silent variant (Hb Campinas, alpha26Ala-->Val). Most of the mutations found reflected the Mediterranean and African origins of the population. Hbs G-Pest and Kurosaki, very rare, and Hb Westmead, common in southern China, were initially described in individuals of ethnic origin differing from those of the carriers reported in the present study and are the first cases to be reported in the Brazilian population.
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OBJECTIVE: To correlate spleen function with soluble transferrin receptor (sTfR) levels and red cell ferritin (RCF) values in patients with sickle cell diseases. DESIGN: Prospective study. LOCATION: University Hospital, School of Medical Sciences, State University of Campinas; a tertiary hospital. PARTICIPANTS: 60 patients with sickle cell diseases, in a steady state, who had not received blood transfusions for 3 months; 28 normal individuals with no clinical or laboratory signs of anemia. MEASUREMENTS: Determination of serum iron, transferrin iron-binding capacity, serum ferritin, RCF and sTfR. Evaluation of spleen function: erythrocytes with pits were quantified. RESULTS: Patients with sickle cell anemia had sTfR levels significantly higher than in normal individuals or those with HbSC (p=0.0001) and there was an inverse correlation between sTfR and fetal Hb (p=0.0016). RCF values were significantly higher in sickle cell anemia patients than in normal individuals or those with HbSC (p=0.0001), and there was a correlation between RCF and pitted erythrocytes (p=0.0512). CONCLUSION: The association between sTfR and fetal Hb confirms the contribution of fetal Hb to improving the hemolytic state by minimizing the consequent reactive erythrocyte expansion. High sTfR levels are not related to the degree of spleen function deficiency seen in sickle cell disease patients. The deficiency in the exocytosis process of the spleen occurring in sickle cell anemia patients may contribute to their accumulation of RCF.
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Clinical, laboratory features and restriction enzyme DNA analysis are reported for a black Brazilian woman with HbH disease. The patient presented a thalassemic blood picture with HbH and Hb Bart's. Gene mapping demonstrated the compound heterozygous state for the --MED and -alpha 3.7 deletions.
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