Intracranial Extramedullary Hematopoiesis in Beta-Thalassemia

Extramedullary hematopoiesis (EMH) represents tumor-like proliferation of hemopoietic tissue which complicates chronic hemoglobinopathy. Intracranial EMH is an extremely rare occurrence. Magnetic resonance imaging (MRI) offers a precise diagnosis. It is essential to distinguish EMH from other extradural central nervous system tumors, because treatment and prognosis are totally different. Herein, we report the imaging findings of beta-thalassemia in a 13-year-old boy complaining of weakness of left side of the body and gait disturbance; CT and MRI revealed an extradural mass in the right temporoparietal region.     

Compliance and satisfaction with deferasirox (Exjade®) compared with deferoxamine in patients with transfusion-dependent beta-thalassemia

Objective

The current standard option for iron chelation therapy (ICT) in transfusion-dependent patients with beta-thalassemia is deferoxamine (DFO). We aimed to compare the compliance with DFO vs. deferasirox (Exjade^®), a novel oral iron chelator, in patients with transfusion-dependent beta-thalassemia.

Methods

In this cross-sectional study, 220 patients from Southern Iran who were receiving DFO or Exjade^® for the last 2 years were investigated in 2012. Satisfaction, compliance, convenience, and life disturbances of the patients with ICT were evaluated. Assessments were performed at four different occasions during 1 year.

Results

According to the results, 114 patients received treatment with DFO and 106 patients were treated with Exjade^®. In comparison with the patients who were treated with DFO, those receiving Exjade^® reported a significantly higher rate of compliance and convenience (P < 0.05). However, no significant difference was observed between the two groups regarding their satisfaction (P > 0.05). In the DFO group, 44.9% of the patients reported irritation and pain at the injection site.

Conclusions

Considering higher rate of compliance and convenience with Exjade^® and the comparable efficacy of these two modalities of ICT documented in previous studies, Exjade^® can be used as a preferable choice of ICT in iron-overload patients with beta-thalassemia.     

Haptoglobin genotypes polymorphism as a risk factor for subclinical atherosclerosis in beta-thalassemia major children; a single center Egyptian study

Abstract

Background/Objectives

Haptoglobin (Hp) is an antioxidant protein. Its genotypic polymorphism had been proposed to influence vascular complications among diabetics, but no data are available about this association among thalassemia patients so far. We have investigated the assumption of an association between Hp genotypes and subclinical atherosclerosis among beta-thalassemia major (TM) children.

Methods

One hundred beta-TM children and 70 matched healthy controls were included. Serum ferritin level and fasting lipid profile were assayed. Haptoglobin genotyping was determined by amplification gel electrophoresis. Carotid intima media thickness (cIMT) was measured using high resolution ultrasound.

Results

The relative distribution of the three Hp genotypes among thalassemia group and the control group were 18 and 14.3% for Hp1-1; 38 and 37.1% for Hp2-1; and 44 and 48.6% for Hp2-2 respectively. There was no significant difference between patients and controls regarding Hp genotypes distribution. Hp2-2 genotype TM children had significantly higher cIMT compared to other genotypes (P < 0.0001). Elevated cIMT was significantly represented in Hp2-2 genotype patients (P < 0.0001) who had higher serum ferritin compared to their counterparts (P < 0.05). Hp2-2 patients were five times more likely to suffer from subclinical atherosclerosis than Hp1-1 and six times than Hp2-1 genotype patients (P = 0.008 and 0.001, respectively); a difference that persisted significant after adjustment for some risk factors compared to Hp2-1 patients (OR 3.96; P = 0.02).

Conclusions

Hp2-2 genotype is a significant predictor for premature atherosclerosis in TM children and confers them an increased risk for iron overload.     

重型β地中海贫血患儿生长发育异常及其与铁超负荷的关系

目的：探讨重型β-地中海贫血患儿生长发育状态及其与铁超负荷的关系。方法：于2007年7~8月对50例长期在该院儿科定期输血的重型β 地中海贫血患儿进行身高、体重和性发育评价，并与1995年中国0~18岁儿童体重、身高百分位数参考值比较，同时检测输血前血常规、肝功能和血清铁蛋白水平。结果：24例（48%）重型β-地中海贫血患儿表现身材矮小，其中15例同时伴体重低下。≥10岁者21例，仅7例出现自发性青春期发育，Tanner II~III期；≥14岁者8例，其中4例尚无性征发育。身高低于第10百分位者（n=31）与身高高于第10百分位者(n=19)分组比较，前者血清铁蛋白水平显著增高（8 239.2±5 865.5 vs 5 028.1±3 885.7 mg/L, P<0.05），输血前Hb水平显著降低(68.2±12.3 vs 79.7±14.5 g/L, P<0.05) ，肝脏显著增大(P<0.05)。而体重低于第10百分位者（n=20）与体重高于第10百分位者（n=30）分组比较，前者仅血清铁蛋白水平差异具有显著意义（9 165.5±6 042.5 vs 5 567.3±4 447.3 mg/L, P<0.05）。结论：接受中等量输血和不正规除铁治疗的重型β-地中海贫血患儿常伴有身材矮小、体重低下和性发育迟缓，其生长发育异常与体内铁严重超负荷有关。     

Pycnodysostosis with heterozygous beta-thalassemia

A 6-year follow-up of a Greek girl with pycnodysostosis associated with heterozygous beta-thalassemia is reported. Active rickets in infancy was superimposed on pycnodysostosis. In the family the autosomal recessive disease, pycnodysostosis, appeared in two of three siblings in combination with the autosomal dominant disease, thalassemia minor.     

Sickle beta-thalassemia presenting as orbital compression syndrome

Orbital compression syndrome is caused by disorders of varying etiologies involving the orbit and presents with ocular and extraocular dysfunction. Ocular involvement of sickle cell disease is uncommon. A 17-year-old male presented with low backache and proptosis of both eyes of 5 days duration without past history of pain crisis or transfusion. Examination revealed pallor, icterus, bilateral proptosis, conjuctival chemosis, and symmetrical restriction of ocular movements with preserved visual acuity. He was drowsy with no other focal deficits. The fundus showed macular edema, venous engorgement, and no hemorrhage. His peripheral smear showed presence of sickle cells. Computed tomography (CT) scan of the orbit revealed orbital subperiosteal hematomas. CT head images showed epidural hematoma in the frontal lobe. High-performance liquid chromatography (HPLC) and mutation studies revealed sickle beta-thalassemia in the patient. He was managed with supportive care, transfusions to keep hemoglobin above 10 g/dl, and hydroxyurea. The patient recovered fully and remained well during follow-up of 12 months. Our case was unique for presenting as orbital compression syndrome without any history of vaso-occlusive crisis.     

地中海贫血羊水及脐血产前基因诊断的临床研究

目的:研究检测α-地中海贫血及β-地中海贫血在产前基因诊断中的临床应用价值.方法:对48例地中海贫血的风险胎儿的羊水(或脐血)应用单管多重PCR体系和反向点杂交法检测α-地中海贫血和β-地中海贫血基因诊断.结果:共有38例胎儿检测出携有地中海贫血.其中α-地贫14例,包括东南亚缺失型杂合子(--SEA/αα)2例,东南亚缺失型纯合子(--SEA--SEA)8例;左缺失型杂合子(-α4.2/αα)1例,右缺失型杂合子(-α3.7/αα)2例,非缺失型点突变(ααT/αα)1例;β-地中海贫血24例,包括CD 41～42杂合子16例,-28(A-G)杂合子3例,双重杂合子3例(ⅣS2nt654/CD41-42,-28(A-G)/CD71-72( A),-α3.7/CD41-42).其中10例重型地贫儿引产,1例重型地贫儿产后新生儿死亡.所有病例经引产或正常分娩后均留取脐带血作地贫基因诊断证实产前诊断.结论:应用单管多重PCR体系及反向点杂交法能快速、准确进行α和β-地中海贫血产前羊水基因检测,这对于有效预防重型地中海贫血胎儿出生具有重大临床意义.     

地中海贫血基因携带者产前筛查及实验室指标的评价

目的：调查本地区围产期妇女地中海贫血（简称“地贫”）基因携带率和基因突变类型，探讨多项实验室指标在产前地中海贫血基因携带者筛查中的临床应用价值。方法：对产前检查的孕妇，作地中海贫血基因分析、血常规红细胞参数检测、血红蛋白电泳HbA2定量以及铁代谢指标血清铁（SI）、血清铁蛋白（SF）测定。对已明确诊断的α地贫组84例、β地贫组85例以及缺铁性贫血（IDA）组76例，进行红细胞参数（RBC、Hb、HCT、MCV、MCH、MCHC、RDW、RET）以及铁代谢指标SF、SI结果的比较；并将各方法检测结果与地中海贫血基因诊断结果比较，分析各筛查方法的敏感性和特异性。结果：3750例孕妇共检出α地贫202例，基因携带率为5．4％；β地贫135例，基因携带率为3．6％。地贫组与IDA组比较，地贫组和IDA组Hb、HCT、MCV、MCH和MCHC均减低，RDW和RET均增高，与健康对照组比较，差异均有统计学意义（P〈0．01）。地贫组MCV减低较IDA组明显，两者之间差异有统计学意义（P〈0．05和P〈0．01）。IDA组SF降低而地贫组SF增高，两者之间差异有统计学意义（P〈0．01）。对照基因检测结果，MCV诊断地贫基因携带者的敏感性为97．6％，特异性为54．5％，若联合SF检测，特异性可达97．0％。HbA2定量对B地贫基因携带者的敏感性为96．8％，特异性为97．4％。结论：MCV结合SF检测可作为产前地贫携带者筛查的简便而有价值的指标。HbA2定量是β地贫携带者筛查可靠的血液学指标。基因诊断的优点是可确定基因突变类型，更可诊断α和β复合型地贫。     

Novel Βeta (β)-Thalassemia Mutation in Turkish Children

Beta (β)-thalassemia is the most frequently observed hereditary blood disorder in the world. It is characterized by deficiency of hemoglobin β-globin gene and is also a profoundly heterogeneous both at the molecular and clinical level. In the case of β-thalassemia, there is reduced (β⁺ type) or absent (β^o type) synthesis of the beta chains of hemoglobin. β-Thalassemia clinically occurs in three main forms: major, intermedia and minor according to requirement of transfusion. The objective of this study was to evaluate β-thalassemia mutations in 89 patients ranging from 2 months to 16 years of age, who enrolled to Medical School Research and Training Hospital, Gaziantep University. The direct DNA sequence analysis was performed for mutation scanning of β-globin gene. 89 children with β-Thalassemia including all types were analyzed, 16 different β-thalassemia mutations were detected. We have also identified a novel mutation (HBB.c.-80delT, rs397509430) in the promoter region (−30 TATA box) of β-globin gene, and clinical data of patient having novel mutation was given. The β-Thalassemia mutations were determined as β-Thalassemia major type in 42 patients (47.19 %), β-Thalassemia intermedia in 4 (4.49 %), β-Thalassemia minor in 43, (48.31 %) patients. The most frequent mutation was IVS I-110 G>A, followed by IVS I-1 G>A, IVS I-6 T>C, IVS II-1 G>A, respectively.     

贵州从江侗族和江口土家族人群β-地中海贫血基因突变型的研究

目的了解β-地中海贫血在贵州从江县侗族、江口县土家族中的基因类型特点、基因型频率及分布规律。方法采用抗碱血红蛋白(HbF)和血红蛋白A2(HbA2)定量测定对人群进行β-地中海贫血初筛,同时应用全自动血细胞分析仪进行RBC、Hb、HCT、MCV、MCH、MCHC、RDW等7项血液学指标分析,用常规酚-氯仿抽提法提取筛查阳性受检者DNA,经PCR-反向点杂交法对β珠蛋白基因进行突变分析。结果受检982人中,共检出52例β-地中海贫血携带者,总检出率为5.27%,其中侗族、土家族检出率分别为7.85%、2.68%;经β珠蛋白突变基因分析,在这两个民族中检出中国人常见3种突变类型:CD17(A→T)无义突变(39例,75.00%),CD41-42(TCTT)移码突变(12例,23.07%)和βE(Codon26)(1例,1.92%)。结论在贵州省少数民族中β-地中海贫血有很高的发病率,基因突变类型具有显著的民族特征,β珠蛋白基因变异情况很独特,可能与族内婚配、家族发病聚集性和通婚地域半径狭小有关。