乙基丙二酸脑病患儿的临床研究及ETHE1基因新突变1例报告

A Chinese girl with ethylmalonic encephalopathy and a novel mutation on ETHE1 gene

目的 1例经EHTE1基因分析确诊的罕见的常染色体隐性遗传病——乙基丙二酸脑病。方法回顾性分析1例确诊乙基丙二酸脑病患儿的临床经过、基因突变特点等。结果女性患儿,7个月起出现顽固性腹泻,并逐渐出现智力运动发育落后及倒退,23个月时检测患儿血液丁酰肉碱4.48 mmol/L,异戊酰肉碱0.7 mmol/L;尿乙基丙二酸及甲基琥珀酸浓度显著增高;颅脑MRI显示双侧基底节区对称性异常信号,符合乙基丙二酸脑病;ETHE1基因分析发现2个杂合突变,其中c.488G>A(p.R163Q)为已知突变,c.203T>C(p.L68P)为未报道的新突变。患儿经免乳糖饮食,以及左卡尼汀、辅酶Q10、维生素B1、维生素B2、维生素C支持治疗后,全身情况改善,智力运动发育有所进步,但仍明显落后。结论尿液乙基丙二酸增高可见于线粒体脂肪酸代谢障碍等多种疾病,血液丁酰肉碱、异戊酰肉碱浓度增高是乙基丙二酸脑病的常见生化表现之一,ETHE1基因分析有助于确诊。

Objective To introduce a case of ethylmalonic encephalopathy which is an autosomal recessive metabolic disorder caused by mutations in the ETHE1 gene. Methods The clinical course and gene mutation in a case of ethylmalonic encephalopathy was retrospectively analysed. Results A previously healthy girl presented with intractable diarrhea from the age of 7 months. Since then, progressive psychomotor regression has been observed. When she was 23 months, her blood butyr-ylcarnitine was signiifcantly increased （4.48μmol/L vs. normal range 0.0~1.0μmol/L）, and isovalerylcarnitine （0.70μmol/L vs. normal range 0.0~0.65μmol/L） was also elevated. Her urine levels of ethylmalonic acid and methylsuccinate acid were markedly increased. Cranial MRI revealed bilateral basal ganglia lesions supporting the diagnosis of ethylmalonic encephalopathy. On her ETHE1 gene, a reported mutation （c.488G〈A, p.R163Q） and a novel mutation （c.203T〈C, p.L68P） were identiifed. After lactose-free dietary treatment and the supplements of L-carnitine, coenzyme Q10, vitamins B1, B2 and C, gradual improvement in general condition, intelligence and motor development has been observed. Conclusions Ethylmalonic aciduria is common in the patients with inborn errors of mitochondrial fatty acid beta-oxidation. In ethylmalonic encephalopathy, elevated blood levels of butyrylcarnitine and isovalerylcarnitine are common and ETHE1 sequencing is helpful in its diagnosis.