Chiou S S, Chang T T, Wu J R, Chang J G, Huang S F, Sheen J M, Tsai S P, Chen T S
Department of Pediatrics, Kaohsiung Medical College, Taiwan, Republic of China.
Gaoxiong Yi Xue Ke Xue Za Zhi. 1995 Feb;11(2):98-109.
Forty-one cases of beta-thalassemia major were assessed for their clinical manifestations and gene mutation. The age distribution was from 1 to 18 years old. Patient's initial clinical symptoms began mostly before 2 years of age (90.2%). Patient's initial hematological data included mean hemoglobin value, 5.8 +/- 1.2 gm/dl, hemoglobin F value, 85.0 +/- 12.1%, hemoglobin A2 value 2.3 +/- 1.8%, reticulocyte count 9.2 +/- 9.0%. Eight different point mutations were characterized. Of these mutations, C to T substitution at nucleotide (nt) 654 of intervening sequence (IVS) 2, accounting for 46.3% of mutant beta-globin genes, is the most common mutation in our series, followed by frameshift codons 41/42 with a four nucleotides (TCTT) deletion for 31.7%; A to G substitution at position -28 of the promotor area for 8.5%; A to T substitution at codon 17 for 6.1%; frameshift codons 27/28 (insertion of C) for 2.4%; G to T substitution at nucleotide 1 of IVS-1 for 2.4%; frameshift codons 71/72 (insertion of A) and IVS-1 3' end TAG-->GAG for 1.2%. The first four mutations account for 92.6% of all beta-globin gene mutations in our series. As to mutations in each individual, the incidence of compound heterozygotes of two different mutations is much higher than homozygotes of a single mutation, 78.0% vs. 22.0%. Compound heterozygotes of C to T substitution at nt 654 of IVS-2 and frameshift codons 41/42 with a four nucleotides deletion is the most common pattern of beta-thalassemia mutation in our patients (41.5%). Patients with beta(0)/-28 beta(+) compound heterozygote mutation had much delayed initial symptoms than beta (0)/beta(0) homozygote mutation, but clinical manifestation may be aggravated when the mutation combined with glucose-6-phosphate dehydrogenase deficiency. Severity of iron overload was significantly correlated with total transfusion amount and patient's age in simple regression analysis (p < 0.001). Splenectomy may effectively prolong transfusion interval, maintain higher hemoglobin level before each transfusion and palliate clinical symptoms (p < 0.01). Iron-chelating agent therapy can effectively lower the total amount of serum ferritin. Higher severity of iron overload correlates with higher incidence of EKG and cardiac abnormalities in patients with beta-thalassemia major.
对41例重型β地中海贫血患者的临床表现和基因突变进行了评估。年龄分布为1至18岁。患者最初的临床症状大多始于2岁之前（90.2%）。患者最初的血液学数据包括平均血红蛋白值5.8±1.2克/分升、血红蛋白F值85.0±12.1%、血红蛋白A2值2.3±1.8%、网织红细胞计数9.2±9.0%。鉴定出8种不同的点突变。在这些突变中，间隔序列（IVS）2的核苷酸（nt）654处的C到T替换，占突变β珠蛋白基因的46.3%，是我们系列中最常见的突变，其次是移码密码子41/42，有四个核苷酸（TCTT）缺失，占31.7%；启动子区域-28位的A到G替换，占8.5%；密码子17处的A到T替换，占6.1%；移码密码子27/28（插入C），占2.4%；IVS-1的核苷酸1处的G到T替换，占2.4%；移码密码子71/72（插入A）和IVS-1 3'端TAG→GAG，占1.2%。前四种突变占我们系列中所有β珠蛋白基因突变的92.6%。至于每个个体中的突变，两种不同突变的复合杂合子发生率远高于单一突变的纯合子，分别为78.0%和22.0%。IVS-2的nt 654处C到T替换与移码密码子41/42有四个核苷酸缺失的复合杂合子是我们患者中最常见的β地中海贫血突变模式（41.5%）。β(0)/-28β(+)复合杂合子突变患者的初始症状比β(0)/β(0)纯合子突变患者延迟得多，但当该突变与葡萄糖-6-磷酸脱氢酶缺乏症合并时，临床表现可能会加重。在简单回归分析中，铁过载的严重程度与总输血量和患者年龄显著相关（p<0.001）。脾切除术可有效延长输血间隔时间，在每次输血前维持较高的血红蛋白水平并缓解临床症状（p<0.01）。铁螯合剂治疗可有效降低血清铁蛋白总量。重型β地中海贫血患者中铁过载的严重程度越高，心电图和心脏异常的发生率越高。
