Thalassaemia major(TM) and Friedreich's ataxia(FA) are autosomal recessive inherited diseases related to the proteins haemoglobin and frataxin respectively. In both diseases abnormalities in iron metabolism is the...Thalassaemia major(TM) and Friedreich's ataxia(FA) are autosomal recessive inherited diseases related to the proteins haemoglobin and frataxin respectively. In both diseases abnormalities in iron metabolism is the main cause of iron toxicity leading to increased morbidity and mortality. Major efforts are directed towards the prevention of these diseases and also in their treatment using iron chelation therapy. Both TM and FA are endemic in Cyprus, where the frequency per total population of asymptomatic heterozygote carriers and patients is the highest worldwide. Cyprus has been a pioneering nation in preventing and nearly eliminating the birth of TM and FA patients by introducing an organized health structure, including prenatal and antenatal diagnosis. Effective iron chelation therapy, improved diagnostic methods and transfusion techniques as well as supportive therapy from other clinical specializations have improved the survival and quality of life of TM patients.Despite the tiresome clinical management regimes many TM patients are successful in their professional lives, have families with children and some are now living well into their fifties. The introduction of deferiprone led to the elimination of cardiac failure induced by iron overload toxicity, which was the major cause of mortality in TM. Effective combinations of deferiprone with deferoxamine in TM patients caused the fall of body iron to normal physiological ranges. In FA different mechanisms of iron metabolism and toxicity apply to that of TM, which can be targeted with specific iron chelation protocols. Preliminary findings from the introduction of deferiprone in FA patients have increased the hopes for improved and effective therapy in this untreatable condition. New and personalised treatments are proposed in TM and FA. Overall, advances in treatments and in particular of chelation therapy using deferiprone are transforming TM and FA from fatal to chronic conditions. The paradigm of Cyprus in the prevention and treatment of TM can be used for application worldwide.展开更多
Endocrine dysfunction in thalassaemia is amongst the most common complication and is principally attributed to excessive iron overload and suboptimal chelation. The prevalence is quite high particularly in multiethnic...Endocrine dysfunction in thalassaemia is amongst the most common complication and is principally attributed to excessive iron overload and suboptimal chelation. The prevalence is quite high particularly in multiethnic populations but determining the prevalence is often difficult due to the widespread heterogeneity of the population and timing of exposure to chelation therapy. Disturbances in growth, pubertal development, abnormal gonadal functions, impaired thyroid, parathyroid and adrenal functions, diabetes and disorderly bone growth are commonly encountered. Early detection and institution of appropriate transfusion regimen and chelation therapy and treatment of complications are the keys to managing this population including regular follow. In this article, we review the literature in relation to the various endocrine complications encountered in thalassaemia.展开更多
Haemoglobinopathies are group of diseases characterized by abnormalities both quantitative and qualitative in the synthesis of haemoglobin. Haemoglobinopathies consist of sickle cell anaemia (SCA), thalassaemia (βT) ...Haemoglobinopathies are group of diseases characterized by abnormalities both quantitative and qualitative in the synthesis of haemoglobin. Haemoglobinopathies consist of sickle cell anaemia (SCA), thalassaemia (βT) and variant haemoglobins. In India, they are responsible for the largest number of genetic disorders and hence are of great public health hazardous. In India major concerned haemoglobinopathic disorders are sickle cell anaemia and β-thalassaemia. Of the several abnormal haemoglobin molecules, four which are widely prevalent in India include: HbS, HbβT, HbE and HbD. Examination of 6463 individuals showed high incidences for haemoglobin variants, HbS and HbβT in different ethnic groups, the frequency being varies from 0% - 20% and 0% - 9% respectively. The frequency of HbS in Brahmins is 4.17%, in Kalar 5.41%, in Rajput 2.04%, in Muslims 3.73% in Maratha 2.08% in Bania 9.09% while in Teli it is 3.65%. Among the Scheduled castes and Nomadic tribal groups HbS ranges from 1% - 12%;in backward caste categories it varies from 3% - 16%;while in Scheduled tribes it ranges from 0% - 20%. The high magnitude of sickle cell trait has been noticed in the Pardhan (20.31%) followed by the Marar (16.10%), the Dhiwar (11.90%), the Gond (11.89%), the Mahar (11.81%) and the Bania (9.90%). A considerable high frequency (9.27%) of β-thalassaemia has been observed among the Sindhi population. Sporadic occurrence of HbβT and HbD among other communities suggested the gradual spread of the genes into the region. The present findings in 11 communities with the thalassaemia syndrome suggest that the β-thalassaemia is accompanied by raised level of HbA2. Unusual greater mean RBC and WBC suggest the high concentration of hypochromic microcytosis in anaemia. The mean MCV and MCH in HbβT and HbD are much lower than the normal ranges compared to HbS. The mean MCHC is much lower in HbβT, HbDD and HbS than the normal range. The cumulative gene frequency of haemoglobinopathies in India is 4.2%. With a population of over 1 billion and a birth rate of 28 per 1000, there are over 42 million carriers and over 12,000 infants are born each year with a major and clinical significant haemoglobinopathy. Out of these, clinically significant sickle cell anaemia and β-thalassaemic disorders account for almost equal numbers.展开更多
The incidence of haemoglobinopathy is high in China,especially south of the Yangtze River.However,the exact status of haemoglobinopathy in Sichuan is unknown.To carry out a detailed research of haemoglobinopathy in in...The incidence of haemoglobinopathy is high in China,especially south of the Yangtze River.However,the exact status of haemoglobinopathy in Sichuan is unknown.To carry out a detailed research of haemoglobinopathy in individuals living in Sichuan,13,298 subjects without clinical symptoms who were living in Sichuan Province,with an age distribution of 5e73 years,were included in this study.Between March 2014 and July 2017,these subjects received examinations at the Medical Lab of Chengdu Women’s&Children’s Central Hospital.Mean corpuscular volume(MCV)<82 fL or mean corpuscular haemoglobin(MCH)<27 pg was used to indicate haemoglobinopathy carriers.Abnormal haemoglobin was screened by electrophoresis,and genes were sequenced to identify genotypes.Genotype diagnosis of alpha-and beta-thalassaemia was carried out by using PCR and shunt hybridization.There were 638 suspected haemoglobinopathy carriers(4.80%,638/13,298).DNA sequencing identified 6 subjects with abnormal haemoglobin genotypes and 15 subjects with Hb E.The frequency of heterozygosity for thalassaemia was 4.12%(1.48%for α-thalassaemia and 2.61%for β-thalassaemia)in Sichuan Province.The mutation spectrum of α-thalassaemia consisted of the five most common mutations:–^(SEA),-α^(3.7),-α^(4.2),α^(CS),and α^(QS).Seven types of β-thalassaemia mutation were found in this study:CD41-42(-TTCT)was the most frequent(28.47%),followed by 17(A>T),28(A>G),and IVS-Ⅱ-654(C>T).The main abnormal haemoglobin genotype(HbE)and thalassaemia genotype(–^(SEA),CD41-42(-TTCT))were consistent with those in other regions of China,but the carrier rate of β-thalassaemia in Sichuan was higher than that of α-thalassaemia.展开更多
目的通过比较7种红细胞参数计算公式对黔南地区儿童缺铁性贫血(IDA)和地中海贫血(TT)的鉴别诊断的效能,选择适合本地区的计算公式,并建立其最佳截断值。方法选取2022年5月至2024年2月在我院就诊的105例患儿为研究对象,根据诊断将其分为T...目的通过比较7种红细胞参数计算公式对黔南地区儿童缺铁性贫血(IDA)和地中海贫血(TT)的鉴别诊断的效能,选择适合本地区的计算公式,并建立其最佳截断值。方法选取2022年5月至2024年2月在我院就诊的105例患儿为研究对象,根据诊断将其分为TT组(55例)和IDA组(50例)。对两组患儿的7个红细胞参数结果和7个红细胞参数计算公式的敏感度(SEN)、特异度(SPE)、约登指数(YI)、阳性预测值、阴性预测值、受试者工作特征曲线下面积(AUC)、根据YI最大值确定的鉴别诊断最佳临界值进行回顾性比较分析。结果TT组的RBC、HBG和MCHC高于IDA组,而MCV、MCH和RDW低于IDA组(P<0.05);Green and King公式鉴别诊断效能最高,其AUC为0.893、SEN为80.0%、SPE为88.0%、YI为68.0%,其最佳截断值为75.9。结论Green and King公式对黔南地区儿童TT和IDA的鉴别诊断能力较好,建议在基层医院推广应用。展开更多
<b><span style="font-family:"">Objective: </span></b><span style="font-family:"">To understand the distribution of thalassemia in all districts under the jur...<b><span style="font-family:"">Objective: </span></b><span style="font-family:"">To understand the distribution of thalassemia in all districts under the jurisdiction of Chongzuo City. <b>Methods:</b> Collect blood routine indicators from May 2014 to 31 December 2020 in the districts of this city to screen out suspected Mediterranean patients for genetic diagnosis;GGAP-PCR and PCR-reverse dot hybridization were used to analyze the thalassemia gene in the specimens of suspected patients;compare the prevalence of thalassemia in the counties and cities within the jurisdiction of this city, and provide corresponding medical advice to the health authorities. <b>Results: </b>21,535 venous blood specimens from patients with suspected thalassemia were collected in the city. There were 14,215 positive cases of thalassemia, accounting for 66.01% of the total number of patients, among which 9455 cases (43.91%) were pure <i>α</i> gene positive. 3464 patients (16.09%) were positive for simple <i>β</i> gene. 1296 patients (6.02%) were positive for <i>αβ</i> double gene. The proportions of thalassemia gene testing for <i>α</i>-thalassaemia gene, <i>β</i>-thalassaemia gene, and <i>α</i>-<i>β</i> double gene in various counties and districts were different. According to the multiple rate or the chi-square test of the constituent ratio, the comparison of the distribution of the thalassaemia gene test results in each area, <i>χ</i><sup>2</sup> = 472.6917, P = 0.0000, the difference is statistically significant. <b>Conclusion:</b> Severe thalassemia is a tragedy for a family. It not only needs to spend a lot of money to prolong life, but it also cannot change the situation of losing life and financial emptiness in the end. It is suggested that timely screening, timely diagnosis and medical consultation should be carried out in <a name="OLE_LINK13"></a>married and unborn families and early pregnancy, so as to reduce the birth of children with severe thalassemia and avoid the occurrence of tragedies.展开更多
目的：综合评价地中海贫血对孕妇妊娠结局的影响,旨为临床决策提供依据。方法：检索Medline、Elsevier、Cochrane Library、ISI web of knowledge、EMBase、中国期刊全文数据库（CNKI）、维普中文科技期刊数据库（VIP）、万方数据库、...目的：综合评价地中海贫血对孕妇妊娠结局的影响,旨为临床决策提供依据。方法：检索Medline、Elsevier、Cochrane Library、ISI web of knowledge、EMBase、中国期刊全文数据库（CNKI）、维普中文科技期刊数据库（VIP）、万方数据库、中国生物医学文献数据库（CBM）从1980年1月至2014年10月发表的关于地中海贫血与孕妇妊娠结局的队列研究,经文献筛选和数据提取后采用Rev Man5.2软件进行Meta分析,采用亚组分析的方法分析异质性的来源,采用漏斗图分析发表偏倚。结果：地中海贫血是孕妇剖宫产、早产发生的危险因素（RR=1.35,95%CI=1.19~1.54,P=0.00;RR=2.06,95%CI=1.29~3.28,P=0.00）,但不是新生儿低体质量发生的危险因素（RR=1.56,95%CI=0.98~2.49,P=0.06）。经亚组分析后,α地中海贫血不是孕妇剖宫产、早产、新生儿低体质量发生的危险因素（RR=1.32,95%CI=0.92~1.91,P=0.14;RR=1.21,95%CI=0.51~2.86,P=0.67;RR=1.27,95%CI=0.52~3.10,P=0.59）;β地中海贫血是剖宫产、新生儿低体质量发生的危险因素,且发生风险分别是正常孕妇的1.54倍和2.31倍（RR=1.54,95%CI=1.20~1.97,P=0.00;RR=2.31,95%CI=1.04~5.14,P=0.04）,但β地中海贫血不是孕妇早产发生的危险因素（RR=2.53,95%CI=0.78~8.18,P=0.12）。结论：地中海贫血是孕妇剖宫产、早产发生的危险因素,β地中海贫血为剖宫产、新生儿低体质量发生的危险因素。展开更多
文摘Thalassaemia major(TM) and Friedreich's ataxia(FA) are autosomal recessive inherited diseases related to the proteins haemoglobin and frataxin respectively. In both diseases abnormalities in iron metabolism is the main cause of iron toxicity leading to increased morbidity and mortality. Major efforts are directed towards the prevention of these diseases and also in their treatment using iron chelation therapy. Both TM and FA are endemic in Cyprus, where the frequency per total population of asymptomatic heterozygote carriers and patients is the highest worldwide. Cyprus has been a pioneering nation in preventing and nearly eliminating the birth of TM and FA patients by introducing an organized health structure, including prenatal and antenatal diagnosis. Effective iron chelation therapy, improved diagnostic methods and transfusion techniques as well as supportive therapy from other clinical specializations have improved the survival and quality of life of TM patients.Despite the tiresome clinical management regimes many TM patients are successful in their professional lives, have families with children and some are now living well into their fifties. The introduction of deferiprone led to the elimination of cardiac failure induced by iron overload toxicity, which was the major cause of mortality in TM. Effective combinations of deferiprone with deferoxamine in TM patients caused the fall of body iron to normal physiological ranges. In FA different mechanisms of iron metabolism and toxicity apply to that of TM, which can be targeted with specific iron chelation protocols. Preliminary findings from the introduction of deferiprone in FA patients have increased the hopes for improved and effective therapy in this untreatable condition. New and personalised treatments are proposed in TM and FA. Overall, advances in treatments and in particular of chelation therapy using deferiprone are transforming TM and FA from fatal to chronic conditions. The paradigm of Cyprus in the prevention and treatment of TM can be used for application worldwide.
文摘Endocrine dysfunction in thalassaemia is amongst the most common complication and is principally attributed to excessive iron overload and suboptimal chelation. The prevalence is quite high particularly in multiethnic populations but determining the prevalence is often difficult due to the widespread heterogeneity of the population and timing of exposure to chelation therapy. Disturbances in growth, pubertal development, abnormal gonadal functions, impaired thyroid, parathyroid and adrenal functions, diabetes and disorderly bone growth are commonly encountered. Early detection and institution of appropriate transfusion regimen and chelation therapy and treatment of complications are the keys to managing this population including regular follow. In this article, we review the literature in relation to the various endocrine complications encountered in thalassaemia.
文摘Haemoglobinopathies are group of diseases characterized by abnormalities both quantitative and qualitative in the synthesis of haemoglobin. Haemoglobinopathies consist of sickle cell anaemia (SCA), thalassaemia (βT) and variant haemoglobins. In India, they are responsible for the largest number of genetic disorders and hence are of great public health hazardous. In India major concerned haemoglobinopathic disorders are sickle cell anaemia and β-thalassaemia. Of the several abnormal haemoglobin molecules, four which are widely prevalent in India include: HbS, HbβT, HbE and HbD. Examination of 6463 individuals showed high incidences for haemoglobin variants, HbS and HbβT in different ethnic groups, the frequency being varies from 0% - 20% and 0% - 9% respectively. The frequency of HbS in Brahmins is 4.17%, in Kalar 5.41%, in Rajput 2.04%, in Muslims 3.73% in Maratha 2.08% in Bania 9.09% while in Teli it is 3.65%. Among the Scheduled castes and Nomadic tribal groups HbS ranges from 1% - 12%;in backward caste categories it varies from 3% - 16%;while in Scheduled tribes it ranges from 0% - 20%. The high magnitude of sickle cell trait has been noticed in the Pardhan (20.31%) followed by the Marar (16.10%), the Dhiwar (11.90%), the Gond (11.89%), the Mahar (11.81%) and the Bania (9.90%). A considerable high frequency (9.27%) of β-thalassaemia has been observed among the Sindhi population. Sporadic occurrence of HbβT and HbD among other communities suggested the gradual spread of the genes into the region. The present findings in 11 communities with the thalassaemia syndrome suggest that the β-thalassaemia is accompanied by raised level of HbA2. Unusual greater mean RBC and WBC suggest the high concentration of hypochromic microcytosis in anaemia. The mean MCV and MCH in HbβT and HbD are much lower than the normal ranges compared to HbS. The mean MCHC is much lower in HbβT, HbDD and HbS than the normal range. The cumulative gene frequency of haemoglobinopathies in India is 4.2%. With a population of over 1 billion and a birth rate of 28 per 1000, there are over 42 million carriers and over 12,000 infants are born each year with a major and clinical significant haemoglobinopathy. Out of these, clinically significant sickle cell anaemia and β-thalassaemic disorders account for almost equal numbers.
基金This work was supported by the National Natural Science Foundation of China(grant number 81370261)the Committee of Health and Family Planning in Sichuan Province(grant number 17PJ521).
文摘The incidence of haemoglobinopathy is high in China,especially south of the Yangtze River.However,the exact status of haemoglobinopathy in Sichuan is unknown.To carry out a detailed research of haemoglobinopathy in individuals living in Sichuan,13,298 subjects without clinical symptoms who were living in Sichuan Province,with an age distribution of 5e73 years,were included in this study.Between March 2014 and July 2017,these subjects received examinations at the Medical Lab of Chengdu Women’s&Children’s Central Hospital.Mean corpuscular volume(MCV)<82 fL or mean corpuscular haemoglobin(MCH)<27 pg was used to indicate haemoglobinopathy carriers.Abnormal haemoglobin was screened by electrophoresis,and genes were sequenced to identify genotypes.Genotype diagnosis of alpha-and beta-thalassaemia was carried out by using PCR and shunt hybridization.There were 638 suspected haemoglobinopathy carriers(4.80%,638/13,298).DNA sequencing identified 6 subjects with abnormal haemoglobin genotypes and 15 subjects with Hb E.The frequency of heterozygosity for thalassaemia was 4.12%(1.48%for α-thalassaemia and 2.61%for β-thalassaemia)in Sichuan Province.The mutation spectrum of α-thalassaemia consisted of the five most common mutations:–^(SEA),-α^(3.7),-α^(4.2),α^(CS),and α^(QS).Seven types of β-thalassaemia mutation were found in this study:CD41-42(-TTCT)was the most frequent(28.47%),followed by 17(A>T),28(A>G),and IVS-Ⅱ-654(C>T).The main abnormal haemoglobin genotype(HbE)and thalassaemia genotype(–^(SEA),CD41-42(-TTCT))were consistent with those in other regions of China,but the carrier rate of β-thalassaemia in Sichuan was higher than that of α-thalassaemia.
文摘目的通过比较7种红细胞参数计算公式对黔南地区儿童缺铁性贫血(IDA)和地中海贫血(TT)的鉴别诊断的效能,选择适合本地区的计算公式,并建立其最佳截断值。方法选取2022年5月至2024年2月在我院就诊的105例患儿为研究对象,根据诊断将其分为TT组(55例)和IDA组(50例)。对两组患儿的7个红细胞参数结果和7个红细胞参数计算公式的敏感度(SEN)、特异度(SPE)、约登指数(YI)、阳性预测值、阴性预测值、受试者工作特征曲线下面积(AUC)、根据YI最大值确定的鉴别诊断最佳临界值进行回顾性比较分析。结果TT组的RBC、HBG和MCHC高于IDA组,而MCV、MCH和RDW低于IDA组(P<0.05);Green and King公式鉴别诊断效能最高,其AUC为0.893、SEN为80.0%、SPE为88.0%、YI为68.0%,其最佳截断值为75.9。结论Green and King公式对黔南地区儿童TT和IDA的鉴别诊断能力较好,建议在基层医院推广应用。
文摘<b><span style="font-family:"">Objective: </span></b><span style="font-family:"">To understand the distribution of thalassemia in all districts under the jurisdiction of Chongzuo City. <b>Methods:</b> Collect blood routine indicators from May 2014 to 31 December 2020 in the districts of this city to screen out suspected Mediterranean patients for genetic diagnosis;GGAP-PCR and PCR-reverse dot hybridization were used to analyze the thalassemia gene in the specimens of suspected patients;compare the prevalence of thalassemia in the counties and cities within the jurisdiction of this city, and provide corresponding medical advice to the health authorities. <b>Results: </b>21,535 venous blood specimens from patients with suspected thalassemia were collected in the city. There were 14,215 positive cases of thalassemia, accounting for 66.01% of the total number of patients, among which 9455 cases (43.91%) were pure <i>α</i> gene positive. 3464 patients (16.09%) were positive for simple <i>β</i> gene. 1296 patients (6.02%) were positive for <i>αβ</i> double gene. The proportions of thalassemia gene testing for <i>α</i>-thalassaemia gene, <i>β</i>-thalassaemia gene, and <i>α</i>-<i>β</i> double gene in various counties and districts were different. According to the multiple rate or the chi-square test of the constituent ratio, the comparison of the distribution of the thalassaemia gene test results in each area, <i>χ</i><sup>2</sup> = 472.6917, P = 0.0000, the difference is statistically significant. <b>Conclusion:</b> Severe thalassemia is a tragedy for a family. It not only needs to spend a lot of money to prolong life, but it also cannot change the situation of losing life and financial emptiness in the end. It is suggested that timely screening, timely diagnosis and medical consultation should be carried out in <a name="OLE_LINK13"></a>married and unborn families and early pregnancy, so as to reduce the birth of children with severe thalassemia and avoid the occurrence of tragedies.
文摘目的：综合评价地中海贫血对孕妇妊娠结局的影响,旨为临床决策提供依据。方法：检索Medline、Elsevier、Cochrane Library、ISI web of knowledge、EMBase、中国期刊全文数据库（CNKI）、维普中文科技期刊数据库（VIP）、万方数据库、中国生物医学文献数据库（CBM）从1980年1月至2014年10月发表的关于地中海贫血与孕妇妊娠结局的队列研究,经文献筛选和数据提取后采用Rev Man5.2软件进行Meta分析,采用亚组分析的方法分析异质性的来源,采用漏斗图分析发表偏倚。结果：地中海贫血是孕妇剖宫产、早产发生的危险因素（RR=1.35,95%CI=1.19~1.54,P=0.00;RR=2.06,95%CI=1.29~3.28,P=0.00）,但不是新生儿低体质量发生的危险因素（RR=1.56,95%CI=0.98~2.49,P=0.06）。经亚组分析后,α地中海贫血不是孕妇剖宫产、早产、新生儿低体质量发生的危险因素（RR=1.32,95%CI=0.92~1.91,P=0.14;RR=1.21,95%CI=0.51~2.86,P=0.67;RR=1.27,95%CI=0.52~3.10,P=0.59）;β地中海贫血是剖宫产、新生儿低体质量发生的危险因素,且发生风险分别是正常孕妇的1.54倍和2.31倍（RR=1.54,95%CI=1.20~1.97,P=0.00;RR=2.31,95%CI=1.04~5.14,P=0.04）,但β地中海贫血不是孕妇早产发生的危险因素（RR=2.53,95%CI=0.78~8.18,P=0.12）。结论：地中海贫血是孕妇剖宫产、早产发生的危险因素,β地中海贫血为剖宫产、新生儿低体质量发生的危险因素。
