Pyruvate Kinase Deficiency Children with New Types of PK-LR Gene Mutation Were Cured by Allogeneic Hematopoietic Stem Cell Transplantation

Abstract

Objective To investigate PK-LR genetic diagnosis and hematopoietic stem cell transplantation (allo-HSCT) of pyruvate kinase deficiency (PKD) through clinical symptoms of two children with PKD and new types of PK-LR gene mutation report.Methods In February 2009 and August 2013,two children with PKD in Shanghai Children's Medical Center,Affiliated to Shanghai Jiao Tong University School of Medicine were collected into this study.The study protocol was approved by the Ethical Review Board of Investigation in Human at Shanghai Children's Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine.Informed consent was obtained from all participants' parents.The blood specimens from the two PKD children were collected.PK-LR gene analysis of two children were detected by Sanger sequencing and whole exon capture sepuencing.Two PKD children were treated by allo-HSCT,and their clinical symptoms,diagnosis and treatment were retrospectively analyzed.Results ① Pyruvate kinase (PK) activation of two PKD children were reduced to 8.00 IU/gHb and 7.61 IU/gHb respectively.② Four types of PK-LR gene missense mutation were found in gene detection of two children.PK-LR gene c.T941T＞C(p.Ile314Thr) mutation was reported formerly,and c.119G＞A (p.Arg40Gln),c.1015G＞A(p.Asp339Asn) and c.848T＞ C (p.Va1283Ala) mutations were new.SIFT function prediction results of the 4 mutations were 0.20,0.37,0 and 0.23 respectively.③ Two PKD children were treated by alloHSCT.After transplantation,myeloid and erythroid hematopoiesis of children 1 were recovered on the 14th day.Platelet (PLT) count was ＞5× 1010/L on the 19th day.Hematopoietic stem cell (HSC) was complete chimerism on the 22th day,and the blood type of children 1 was converted to donor's.After transplantation,myeloid and erythroid hematopoiesis of children 2 were recovered on the 12th day.PLT count was ＞3× 1010/L on the 19th day.HSC was complete chimerism on the 18th day,and the blood type of children 2 was converted to donor's.Conclusions The whole exon capture sequencing can be used in the clinical diagnosis of PKD and searching for new types of PK-LR gene mutation.PK-LR gene c.119 G＞A (p.Arg40Gln),c.1015G＞A(p.Asp339Asn) and c.848T＞C(p.Va1283Ala) missense mutations could also lead to PKD.allo-HSCT could be an effective treatment for PKD. Key words: Pyruvate kinase deficiency of red cells; Mutation,missense; Hematopoietic stem cell transplantation