成年期Ⅰa型糖原累积症致继发性骨质疏松症家系研究  

Glycogen storage disease Ⅰa diagnosed in adult causes secondary osteoporosis: a pedigree study

作　　者：祝捷[1] 邢燕[2] 郑茂[1] 王东[1] 邢学农[1] 叶山东[1] 

机构地区：[1]安徽医科大学附属省立医院内分泌科,合肥230001 [2]安徽医科大学附属省立医院内分泌实验室,合肥230001

出　　处：《中华骨质疏松和骨矿盐疾病杂志》2014年第1期25-29,共5页Chinese Journal Of Osteoporosis And Bone Mineral Research

基　　金：安徽省临床重点发展学科基金(ZF0010)

摘　　要：目的研究Ⅰa型糖原累积症致继发性骨质疏松症家系及其分子遗传学背景。方法使用双能X射线骨密度仪检测先证者及其弟左前臂、左髋关节、腰椎的骨密度。抽取先证者及其父母全血,提取基因组DNA,通过多聚酶链反应扩增葡萄糖-6-磷酸酶5个外显子及与内含子交界区,采用DNA直接测序法确定突变部位。结果先证者及其弟腰椎及左髋部骨密度均低于同龄人,其弟左前臂骨密度低于同龄人。先证者G6PC基因第5号外显子存在c.648G>T纯合突变,其父母均存在c.648G>T杂合突变。结论Ⅰa型糖原累积症是导致成人继发性骨质疏松症的罕见病因。成人发生原因不明的骨质疏松,合并肝脏肿大、高脂血症、高尿酸血症和血乳酸水平明显增高时,应考虑糖原累积症。其导致骨质疏松的机制以及表型和基因型的关系有待进一步研究。Objective To investigate the molecular genetic background of a pedigree with glycogen storage dis -easeⅠa （ GSDⅠa） and focus on secondary osteoporosis caused by the disease .Methods The proband and her younger brother underwent bone mineral density （BMD） measurement by dual-energy X-ray absorptiometry （DEXA） for spine, left forearm and hip .DNA was extracted from the peripheral blood of the proband and her father and mother .All the five exons and the flanking introns of the glucose-6-phosphatase gene were amplified by polymerase chain reaction .Actual mu-tations were confirmed by direct sequencing .Results Spine BMD and left hip BMD of the patients were below the expec-ted range for age .Left forearm BMD of the proband＆#39;s younger brother was below the expected range for age .The DNA-based analysis revealed that the proband was homozygous for the c.648G＆gt;T mutation.The proband＆#39;s father, as well as her mother was heterozygous for the c.648G＆gt;T mutation.Conclusions GSDⅠa is an extremely rare cause of seconda-ry osteoporosis in adult.Adult who has unexplained osteoporosis , hepatomegaly, hyperlipemia, hyperuricemia and a marked increase of blood lactic acid concentration should be screened for GSD .The pathogenesis and the genotype-pheno-type correlation require further research .

关 键 词：糖原累积症 骨质疏松症 家系研究 

分 类 号：R725.8[医药卫生—儿科]