北京市新生儿短链酰基辅酶A脱氢酶缺乏症筛查、临床特征及基因突变分析

Clinical characteristics and related gene mutations of infants with short-chain acyl-CoA dehydrogenase deficiency by neonatal screening in Beijing

目的:探讨北京市新生儿短链酰基辅酶A脱氢酶缺乏症(SCADD)的发病率、临床特征及基因突变特点。方法:采用串联质谱法检测2014年8月至2022年3月北京市100603名新生儿干血斑中酰基肉碱水平,采用气相色谱-质谱法检测尿有机酸,高通量测序检测基因突变。对SCADD确诊患儿进行临床、生化指标检查及基因突变特点分析,并随访患儿的生长发育和智能发育情况。结果:100603名活产新生儿中初筛丁酰基肉碱(C4)浓度升高或伴C4/丙酰基肉碱(C3)比值升高196名,召回131名新生儿,确诊SCADD患儿5例,SCADD发病率为4.97/10万(1/20121)。5例确诊患儿均无明显临床表现,血C4及C4/C3比值均增加,其中4例尿乙基丙二酸增加。5例确诊患儿中,ACADS基因检测到7种突变,均为已报道错义突变,其中1例患儿为纯合突变,其余均为复合杂合突变。5例患儿的随访年龄中位数为33(4~40)个月,随访期间均未出现临床症状,体格及智力发育正常。结论:北京市SCADD发病率为1/20121,通过新生儿筛查确诊的SCADD患儿无明显临床症状,预后较好。

Objective:To investigate the clinical characteristics of infants with shortchain acyl-CoA dehydrogenase deficiency(SCADD)and related gene mutations in Beijing.Methods:The acylcarnitine levels in the blood samples of 100603 neonates in Beijing during August 2014 and March 2022 were measured by tandem mass spectrometry(MS/MS).The suspected SCADD neonates were rechecked by MS/MS,urine gas chromatography-mass spectrometry(GC/MS)and next-generation sequencing(NGS)for diagnosis.The clinical,biochemical and gene mutation characteristics of infants with SCADD were analyzed;the growth and intellectual development of these patients were observed regularly.Results:Among 100603 live births,the elevated C4 concentration or elevated C4/C3 ratio were detected in the initial screening from 196 neonates,and 131 were recalled.Five cases of SCADD were diagnosed with an incidence rate of 4.97/100000(1/20121).There was no significant abnormality in clinical manifestations,however,the blood butyrylcarnitine(C4)level and the ratio of C4 to propionylcarnitine(C3)were raised in all diagnosed cases.Urinary organic acids were analyzed in 4 cases,all of whom had increased ethyl malonate acid levels.Seven mutations were detected in the ACADS gene,all of which were known missense mutations.One patient had homozygous mutation,and the others showed compound heterozygous mutations.No clinical symptoms were observed,and the physical and intellectual development was normal in all patients at a median age of 33(4-40)months during follow-up.Conclusions:The incidence rate of SCADD was 1/20121 in Beijing.Neonates with early diagnosis and without clinical symptoms usually have good prognosis.