先天性糖基化障碍1例临床和基因分析

Clinical and genetic analysis for congenital disturbance of glycosylation with MPI gene mutation

目的探讨甘露糖磷酸异构酶(MPI)基因突变所致先天性糖基化障碍(CDG)的临床和基因突变特点。方法回顾分析1例因肝肿大而被发现的MPI基因缺陷所致CDG患儿的临床资料,以及患儿及其父母基因检测结果。结果患儿,女,1岁左右发现肝脏进行性肿大,伴慢性腹泻、反复呼吸道感染等;体格检查发现肝脏肋下4 cm、脾脏肋下1 cm;腹部MRI提示肝大伴弥漫性密度改变。采用高通量测序法,发现患儿MPI基因(NM_002435. 2)第4号外显子存在2个杂合错义变异c.391G>A,p.Asp131Asn和c.455G>A,p.Arg152Gin,均为人群中极低频率的变异;家系分析显示父亲携带c.391G>A,p.Asp131Asn错义变异,母亲携带c.455G>A,p.Arg152Gin错义变异,确诊为CDG-Ib型。结论 CDG是一组由常染色体隐性遗传引起的糖蛋白合成缺陷的代谢性疾病,基因检测有助于明确诊断。

Objective To investigate the clinical manifestations and gene mutation characteristics for congenital disorders of glycosylation caused by MPI gene mutation.Method One case with liver enlargement was diagnosed as congenital disturbance of glycosylation(CDG).We analyzed the clinical data and laboratory examination result,and the gene mutations identified by Sanger sequencing.Result The patient was a girl,the main clinical features are hepatomegaly,recurrent respiratory infection,chronic diarrhea that started from 1 year old.Physical examination showed that the liver is 4 cm and the spleen is 1 cm under the ribs.The abdominal MRI results were hepatomegaly with diffuse lesions.Genetic analysis showed that the patient carried compound heterozygous mutations of c.391 G>A(p.Asp131 Asn)and c.455 G>A(p.Arg152 G)in MPI gene(NM002435.2),which were inherited from father and mother,respectively.Conclusion CDG is a metabolic disease caused by a group of autosomal recessive glycoprotein synthesis defects.MPI gene defect mainly manifested as hepatomegaly,vomiting,diarrhea,lymphangiectasis,protein losing enteropathy,hypoglycemia,the suspected cases can get a definite diagnosis by gene detection.