The β-GLobin Gene Haplotypes Associated With Hb D-Los Angeles [β121(GH4)Glu→Gln] in Western Iran

Hb D-Los Angeles is characterized by the substitution of glutamine for glutamic acid at position 121 of the β-globin chain. The present investigation is the first study on the β-globin gene haplotypes associated with β-D-Los Angeles in Western Iran. Thirty two individuals from 11 unrelated families from Western Iran were studied. The Hb D-Los Angeles status of all cases was confirmed using polymerase chain reaction (PCR) followed by digestion with EcoRI. The haplotype of the β‐globin gene cluster was determined by a PCR-RFLP (restriction fragment length polymorphism) procedure. The haplotype background of the β^A chromosomes was also determined in 35 normal subjects from the same geographic region. The β-globin gene haplotype analysis demonstrated that all β-D-Los Angeles genes (23 genes) were in linkage disequilibrium with haplotype I [+????++]. Among the 70 β^A chromosomes, 30 chromosomes (42.9%) were associated with haplotype I. The present study indicates the unicentric origin of the β-D-Los Angeles gene in Western Iran. It seems that this mutation may have occurred at the same chromosomal background common in the local population.     

Hb Bleuland [α108(G15)Thr→Asn,ACC→AAC (α2)]: A New Abnormal Hemoglobin Associated with a Mild α-Thalassemia Phenotype

We report a new structural defect of the α2-globin chain, not detectable on high performance liquid chromatography (HPLC) or electrophoresis, characterized in a 12-year-old boy of Surinamese-Hindustani origin. The child was suspected to be a carrier of α-thalassemia (thal) because of microcytic hypochromic parameters in the absence of iron depletion. Gap-polymerase chain reaction (gap-PCR) revealed only normal fragments in the proband, and the pattern of a ?α^4.2 (leftward) deletion in his father and sister. Direct sequencing of the α-globin genes revealed an ACC→AAC transversion at codon 108 of the α2-globin gene in the proband, in his mother and in a younger sister. The new mutation predicts a Thr →Asn amino acid substitution at the corresponding residue. Threonine, a covalent binder with an R-active OH group, situated in the G helix of the α-globin chain, is involved in α1β1 contacts. Asparagine, being an equally covalent binder but with a different R-active H₂N-C=O group, could make the mutated chain less suitable for tetramer cooperation. Alternatively, an absent or reduced interaction with the α hemoglobin (Hb) stabilizing protein (AHSP) could lead to loss of α chains. Hb Bleuland is the first mutation described at codon 108 and is therefore interesting in regard to the possible effects and genetic risk. The nearest variant, Hb Suan-Dok [α109(G16)Leu →Arg, CTG→CGG (α2)] was originally observed in a Thai patient affected with Hb H, in combination with an α⁰-thal allele. The same Hb Suan-Dok mutation, recently described in our laboratory in a carrier of African ancestry, was also not detectable as a protein and presented with an α-thal phenotype similar to Hb Bleuland.     

HB Fannin-Lubbock-I with A Single GGC>GAC Mutation at β119(GH2)Gly→Asp in a Homozygous Mexican Patient

We studied a fast-moving, abnormal hemoglobin (Hb) identified as Fannin–Lubbock-I [β119(GH2)Gly→Asp] in a homozygous Mexican girl. To date, homozygosity for the Hb Fannin-Lubbock-I variant has not been reported. Her parents and five other relatives were heterozygotes. The 5′ β-globin haplotype analysis showed that the mutation was associated with haplotype 2 [? + + ? +]for the ε, ^Gγ, ^Aγ, 5′ and 3?′ψβ-globin sites, and also segregated with the TGTTC haplotype, which was constructed with five polymorphic sites of the β-globin gene [exon 1-nucleotide (nt) 6 (C>T) and IVS-II-16 (C>G), IVS-II-46 (T>C), IVS-II-74 (G>T), and IVS-II-81 (C>T). In 1994, a variant with an additional mutation at codon 111 [β111(G13)Val→Leu] was described in five Spanish families. This variant was termed Hb Fannin-Lubbock-II, and the question of the existence of Hb Fannin-Lubbock-I arose. However, based on our findings, we were able to confirm the existence of Hb Fannin-Lubbock-I and propose that this mutation has a different origin from the one identified in Spanish families.     

Haemoglobin Hallamshire (β146 HIS → TYR): a new high oxygen affinity haemoglobin responsible for familial erythrocytosis

Summary A new high oxygen affinity haemoglobin with the β chain mutation β146 HIS → TYR is described. This variant was detected in a fit 34-year-old man with true erythrocytosis. The abnormal haemoglobin was identified as an extra band on cellulose acetate electrophoresis at pH 6.3 and was later confirmed by β globin gene sequencing and oxygen dissociation studies. Whole blood containing Haemoglobin Hallamshire has a P50 of 18 mmHg. This newly described haemoglobin variant was also responsible for erythrocytosis in the mother and maternal half cousin of the index case. The identification of Haemoglobin Hallamshire provides confirmatory evidence of the important role of the C-terminal end of the chain in haemoglobin function.     

Sickle cell anemia with few painful crises is characterized by decreased red cell deformability and increased number of dense cells.

The frequency and severity of the painful sickle cell crisis vary greatly among affected patients. Aside from a high level of Hb F(greater than 20%) there is no established parameter which may modulate the clinical severity of the disease. In this paper we describe two groups of adult patients with homozygous SS and present their characteristics. The division into these two groups was on the basis of relatively low RBC deformability (less than or equal to 37% of control) and high RBC deformability (greater than 65% of control) in the steady state. None of the patients had alpha-gene deletion and all had Hb F level less than 6.0%. Each patient was followed for a minimum of 3 years. The number of dense cells was quantitated by centrifugation on discontinuous Stractan gradient. RBC deformability index in isotonic medium (DI 290) was determined by ektacytometry and expressed as % of control. The patients with low RBC deformability had significantly less painful crises and more leg ulcers than those patients with high RBC deformability. The average number of dense cells was 22.2% and 9.8% of total circulating cells in the first and second group respectively. Moreover, the group with high red cell deformability had 33% mortality during the study period whereas no deaths occurred in the group with low RBC deformability. The data indicate that there is a subset of patients with SS who have relatively few painful crises despite low Hb F level. We wish to designate these by the acronym MIDDD syndrome: Mild disease as far as painful crises are concerned, increased number of Dense cells, and Decreased red cell Deformability. In addition these patients have high incidence of leg ulcers, have low incidence of urinary tract infection, and less mortality. Cellular factors seem to contribute to the incidence of painful crises.     

Antioxidant system and serum trace elements in alpha-thalassaemia and Hb Lepore trait

Erythrocyte antioxidant enzymes, superoxide dismutase, catalase and glutathione peroxidase were found to be significantly high in subjects with alpha-thalassaemia and Hb Lepore trait, as a consequence of the increased oxidant stress which is known to exist in these conditions. Among the serum trace elements present in these enzymes, selenium was increased in subjects with Hb Lepore trait and significantly low in those with alpha-thalassaemia trait, while selenium erythrocyte content was significantly increased in alpha-thalassaemic subjects.     

癌性贫血时血清促红细胞生成素变化的相关研究

目的 分析癌性贫血患者血清促红细胞生成素（Epo）水平及其与血红蛋白（Hb）水平的关系。方法 对53例癌性贫血、71例癌症无贫血和21例正常对照的血清用ELISA法检测Epo值；并对53例癌性贫血患者的Hb和Epo值与缺铁性贫血（IDA）患者相比较，以及根据Hb值进行分层分析。结果 ①癌性贫血组、癌症无贫血组、对照组的血清Epo分别为（63．08±104，1）mu／ml、（13．73±9．96）mu／ml和（8．10±4．97）mu／ml。癌性贫血组与癌症无贫血组及与对照组相比较有统计学意义（分别为P〈0.01和P〈0.01）。癌症无贫血组与对照组无统计学意义（P〉0.05）。②癌性贫血患者的Epo水平与Hb水平存在负相关（r=-0．693，P〈0.001）。③癌性贫血患者的Epo水平低于同样程度贫血的IDA患者（P〈0.01）。④轻度癌性贫血患者的Epo水平明显低于中重度癌性贫血患者。结论癌性贫血患者的Epo值高于癌症无贫血患者和正常人，并与Hb值呈负相关；随着贫血的加重，Epo水平逐渐升高；但低于同样程度贫血的IDA患者。     

应用重组促红细胞生成素治疗长期血透患者的贫血

作者应用重组促红细胞生成素(rHuEPO)治疗68例依赖输血的透析患者(醋酸盐血透32例,碳酸氢盐血透24例,血液滤过12例)。治疗前 Hb 52.7±8.0g/L,Ht19.4±2.2%,血清铁蛋白>100μg/L。rHuEPO 治疗剂量150～300 u·kg~(-1)/周,静脉推注。当 Hb>100～120g/L,Ht>30%～35%时将 rHuEPO 减至维持量。疗程6.2±4.3个月。所有患者经 rHuEPO 治疗后不再输血,Hb 和 Ht 均有不同程度上升。其中39例 Hb 净增大于60g/L,Ht 增加大于10%,分别占治疗病例的57.4%。结果表明,rHuEPO 剂量为150～300 u·kg~(-1)/周是安全有效的,副作用远较国外报道为低。     

Intrathoracic extramedullary hematopoietic tumor in hemoglobin H disease.

We report a Chinese patient with hemoglobin H (Hb H) disease who developed intrathoracic extramedullary hematopoiesis (EMH) 17 years following splenectomy for a blunt abdominal injury. The patient initially presented with extreme hyperbilirubinemia and multiple intrathoracic tumors. Hb H disease was diagnosed after investigation, and the marked jaundice, which declined gradually after supportive treatment, was attributed to his chronic hemolysis superimposed on an acute hepatitis C virus infection. A biopsy of the intrathoracic tumors revealed an EMH. Intrathoracic EMH, which is usually encountered in patients with beta-thalassemia and hereditary spherocytosis, has never been reported in Hb H disease. In areas where thalassemia is prevalent, EMH should be considered in the differential diagnosis of patients who have chronic anemia with asymptomatic intrathoracic tumor to avoid unnecessary surgical interventions.