误诊为血液病的1例乙基丙二酸脑病患儿的临床及基因分析

Clinical and Genetic Analysis of A Case of Ethylmalonic Acid Encephalopathy Present with Hematopathy

目的探讨1例因皮肤瘀斑和出血点就诊的乙基丙二酸脑病患儿的临床及基因突变特点。方法总结分析1例乙基丙二酸脑病患儿的临床资料。应用高通量测序技术对患儿及父母进行全外显子基因变异分析,并应用Sanger测序对患儿的哥哥进行家系验证。结果 4月龄患儿为孕足月顺产,出生体质量3 100 g。围生期无异常。出生后喂养困难、出生后10 d余出现腹泻,伴发育落后、皮肤瘀斑,凝血功能未见异常,血乳酸增高。血串联质谱遗传代谢病检测结果:丁酰肉碱及异戊酰肉碱明显增高;尿有机酸串联质谱遗传代谢病项目分析显示:乙基丙二酸及异戊酰甘氨酸增高。基因检测发现患儿的ETHE1基因c.247dup/p.D83Gfs*24 (CDS3亚区)和c.277-1 G>T(intron2亚区)复合杂合突变,突变分别来自患儿父母。结论乙基丙二酸脑病可累及脑、胃肠、血管等,引起多脏器损害,临床表现为智力运动发育落后、顽固性腹泻、凝血功能正常而有皮肤瘀斑、直立性手足发绀,ETHE1基因c.247dup/p.D83Gfs*24(CDS3亚区)和c.277-1G>T(Intron2亚区)复合杂合突变是患儿的致病原因,此新变异丰富了ETHE1基因的突变谱。

Aim To investigate clinical and genetic analysis of a case of ethylmalonic acid encephalopathy present with skin ecchymosis and bleeding spots. Methods The clinical data of a 4-monthold child were summarized. The whole exon gene variation of the child and his parents was analyzed by high-throughput sequencing technology, and the family of the elder brother of the child was verified by Sanger sequencing. Results The baby was born in full-term with a birth weight of 3100 g. There was no abnormality in perinatal period. The heterozygous mutations of C.247 dup/P.d83 gfs*24(cds3 subdomain) and C.277-1 G>T(intron2 subdomain) in ETHE1 gene were detected by gene testing. The mutations were from the parents of the children respectively. Conclusion Ethylmalonic acid encephalopathy can involve the brain, gastrointestinal, vascular and other organs, causing multiple organ damage. The clinical manifestations are mental retardation, intractable diarrhea, skin ecchymosis with normal blood coagulation function, erect cyanosis of hands and feet, C.247 dup/P.d83 gfs *24(cds3 subregion) and C.277-1 of ETHE1 gene G> T(intron2) complex heterozygous mutation is the cause of the disease in the children. The above new mutations enrich the variation of ETHE1 gene.