中文摘要：

目的报告一个遗传性铁粒幼细胞贫血（CSA）家系并进行文献复习，以提高对CSA发病机制及其治疗的认识。方法检测先证者及其家族成员外周血血常规及铁代谢相关指标；应用基因组-DNAPCR技术扩增先证者及其家族成员6-氨基v酮戊酸合成酶2（ALAS2）基因第1-11号外显子，应用直接测序法检测外显子突变状态，采用T载体连接测序鉴定其突变类型。结果先证者血常规检查示小细胞低色素性贫血（血红蛋白84g／L、红细胞平均体积64fl、红细胞平均血红蛋白含量16．5Pg），血清铁44．7μmol／L、血清铁蛋白3123μg／L，转铁蛋白饱和度O．84。基因分析显示先证者与先证者母亲、胞妹及侄女ALAS2基因第5号外显子466碱基A〉G杂合突变，引起156位氨基酸由赖氨酸转变为谷氨酸。家系成员分析示该家系为x-连锁铁粒幼细胞贫血（XLSA），男性ALAS2基因突变半合子发病，女性该基因突变携带者均无贫血表现，仅有红细胞分布宽度的异常。先证者接受持续1年的维生素B。联合去铁治疗，血红蛋白升至98g／L，血清铁蛋白降至1580μg／L。结论该家系为中国一新发现的XLSA家系，ALAS2基因K156E突变为其致病基因；CSA的诊断有赖于相关基因突变分析，维生素B。是CSA的首选治疗药物。

英文摘要：

Objective To raise awareness of molecular pathogenesis and treatment of congential sideroblastic anemia （CSA）. Methods A complete blood count and iron metabolism were detected from the proband and other members of the family. Mutation analysis was performed on the complete coding regions of ALAS2 gene by common polymerase chain reaction （PCR） using genomic DNA as a template from memebers the family. ALAS2 mutations were detected by direct sequencing and mutation types were confirmed by sequencing followed by plasmid cloning. Results The proband male presented with microcytic hypochromic anemia （hemoglobin 84 g/L, mean corpuscular volume 64 fL, mean corpuscular hemoglobin 16.5 μg）, and iron overload （serum iron 44.7 μmol/L, serum ferritin 3 123 μg/L and transferrin saturation 0.84）. A mutation 466 A〉G predicting a Lys156Glu amino acid change was identified in the proband and 3 females from the family. The proband was hemizygous for this mutation and presented with microcytic anemia and iron overload, while all 3 heterozygous females showed marginally increased red- cell distribution width without any other symptoms. The proband treated with 300 mg of pyridoxine per day and iron chelation therapy with deferoxamine for one year had durable hematopoietic improvements, including increase in hemoglobin to 98 g/L and decrease in serum ferritin to 1 580 μg/L. Conclusion This was a novel K156E substitution in ALAS2 gene identified in a 3-generation pedigree in China. Our findings emphasized the importance of gene based diagnosis of CSA, and CSA patient with ALAS2 mutation responded to pyridoxine treatment.