背景:戊二酸血症1型(GA1)是一种罕见的常染色体隐性遗传代谢疾病,由编码戊二酰辅酶A脱氢酶(GCDH)的基因变异引起。GA1的估计患病率和GCDH基因的突变谱因种族和地区而异。这项研究的目的是评估福建省GA1患者的酰基肉碱概况和遗传特征。中国东南部。
结果:从2014年1月至2022年12月,在福建省6个新生儿筛查(NBS)中心,使用MS/MS对1,151,069名新生儿(男性631,016名,女性520,053名)进行了筛查,并招募了本研究。通过NBS,18名新生儿(13名女性和5名男性)被诊断为GA1。因此,福建省63948例新生儿中GA1的估计发病率为1。此外,临床诊断后招募了17例GA1患者。除一名GA1患者外,所有患者的戊二酰肉碱(C5DC)浓度均显着增加。对33例患者的尿有机酸分析结果表明,所有患者的戊二酸(GA)浓度均增加。通过NBS鉴定的患者的C5DC和GA水平高于通过临床诊断鉴定的患者(P<0.05)。在GA1患者中共检测到70个等位基因的71个变体,其中鉴定出19个不同的致病变体。三个最普遍的变体占总数的73.23%,c.1244-2A>C,p.(?)(63.38%),c.1261G>A,p.Ala421Thr(5.63%),c.406G>T,p.Gly136Cys(4.22%)。观察到的最丰富的基因型是c。[1244-2A>C];[1244-2A>C](18/35,52.43%),其表型对应于高排泄物(HE,GA>100mmol/molCr)。
结论:结论:我们调查了35例无关GA1患者的生化和分子特征.干血斑点和尿GA中的C5DC浓度是GA1诊断的有效指标。我们的研究还确定了福建省GA1患者的GCDH变异谱,中国东南部。基因型和表型之间的相关性分析为遗传咨询和管理提供了初步和有价值的信息。
Glutaric acidemia type 1 (GA1) is a rare autosomal recessive inherited metabolic disorder caused by variants in the gene encoding the enzyme glutaryl-CoA dehydrogenase (GCDH). The estimated prevalence of GA1 and the mutational spectrum of the GCDH gene vary widely according to race and region. The aim of this study was to assess the acylcarnitine profiles and genetic characteristics of patients with GA1 in Fujian Province, southeastern China.
From January 2014 to December 2022, a total of 1,151,069 newborns (631,016 males and 520,053 females) were screened using MS/MS in six newborn screening (NBS) centers in Fujian Province and recruited for this study. Through NBS, 18 newborns (13 females and 5 males) were diagnosed with GA1. Thus, the estimated incidence of GA1 was 1 in 63,948 newborns in Fujian province. In addition, 17 patients with GA1 were recruited after clinical diagnosis. All but one patient with GA1 had a remarkable increase in glutarylcarnitine (C5DC) concentrations. The results of urinary organic acid analyses in 33 patients showed that the concentration of glutaric acid (GA) increased in all patients. The levels of C5DC and GA in patients identified via NBS were higher than those in patients identified via clinical diagnosis (P < 0.05). A total of 71 variants of 70 alleles were detected in patients with GA1, with 19 different pathogenic variants identified. The three most prevalent variants represented 73.23% of the total and were c.1244-2 A > C, p.(?) (63.38%), c.1261G > A, p.Ala421Thr (5.63%), and c.406G > T, p.Gly136Cys (4.22%). The most abundant genotype observed was c.[1244-2 A > C]; [1244-2 A > C] (18/35, 52.43%) and its phenotype corresponded to high excretors (HE, GA > 100 mmol/mol Cr).
In conclusion, we investigated the biochemical and molecular features of 35 unrelated patients with GA1. C5DC concentrations in dried blood spots and urinary GA are effective indicators for a GA1 diagnosis. Our study also identified a GCDH variant spectrum in patients with GA1 from Fujian Province, southeastern China. Correlation analysis between genotypes and phenotypes provides preliminary and valuable information for genetic counseling and management.