CAJ | 학술논문

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-DNA PCR技术扩增先证者及其家族成员δ-氨基γ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84 g/L、红细胞平均体积64 f1、红细胞平均血红蛋白含量16.5 pg),血清铁44.7 μmol/L、血清铁蛋白3 123 μg/L,转铁蛋白饱和度0.84.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B6联合去铁治疗,血红蛋白升至98 g/L,血清铁蛋白降至l 580 μg/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B6是CSA的首选治疗药物.
목적 보고일개유전성철립유세포빈혈(CSA)가계병진행문헌복습,이제고대CSA발병궤제급기치료적인식.방법 검측선증자급기가족성원외주혈혈상규급철대사상관지표；응용기인조-DNA PCR기술확증선증자급기가족성원δ-안기γ동무산합성매2(ALAS2)기인제1～11호외현자,응용직접측서법검측외현자돌변상태,채용T재체련접측서감정기돌변류형.결과 선증자혈상규검사시소세포저색소성빈혈(혈홍단백84 g/L、홍세포평균체적64 f1、홍세포평균혈홍단백함량16.5 pg),혈청철44.7 μmol/L、혈청철단백3 123 μg/L,전철단백포화도0.84.기인분석현시선증자여선증자모친、포매급질녀ALAS2기인제5호외현자466감기A＞G잡합돌변,인기156위안기산유뢰안산전변위곡안산.가계성원분석시해가계위X-련쇄철립유세포빈혈(XLSA),남성ALAS2기인돌변반합자발병,녀성해기인돌변휴대자균무빈혈표현,부유홍세포분포관도적이상.선증자접수지속1년적유생소B6연합거철치료,혈홍단백승지98 g/L,혈청철단백강지l 580 μg/L.결론 해가계위중국일신발현적XLSA가계,ALAS2기인K156E돌변위기치병기인；CSA적진단유뢰우상관기인돌변분석,유생소B6시CSA적수선치료약물.
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 pg),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 Lysl56Glu 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 redcell 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.