福建泉州地区新生儿氨基酸代谢障碍的筛查结果分析

目的 了解福建省泉州地区新生儿氨基酸代谢障碍（amino acid disorders,AAD）的总体筛查概况。方法 应用串联质谱技术对泉州地区2014 年1 月~2018 年11 月期间364 545 例新生儿进行遗传代谢病筛查,对可疑阳性患儿进行相关致病基因检测,统计分析确诊AAD 的种类、疾病构成和发病率。结果 共确诊AAD 患儿42 例,AAD 总发病率为1∶8 680。确诊10 种不同的AAD,其中最常见的苯丙氨酸羟化酶缺乏症14 例（33.3%）,其次为希特林蛋白缺乏症10 例（23.8%）,其余的分别为四氢生物蝶呤缺乏症4 例（9.5%）、非酮性高甘氨酸血症3 例（7.1%）、甲硫氨酸腺苷转移酶I/III 缺乏症3 例（7.1%）、瓜氨酸血症I 型2 例（4.8%）、精氨酰代琥珀酸尿症2 例（4.8%）和鸟氨酸氨甲酰转移酶缺乏症2 例（4.8%）;氨甲酰磷酸合成酶缺乏症和高脯氨酸血症较罕见,各确诊1 例。结论 福建省泉州地区新生儿AAD 的疾病构成和发病率等特征的阐明可为该地区的出生缺陷防控提供科学依据与指导。     

新生儿异戊酸血症串联质谱法与相关基因突变检测的价值研究

目的　了解福建省泉州地区新生儿异戊酸血症（isovaleric acidemia, IVA）串联质谱法与相关基因突变检测情况。方法　2019 年1 月～ 2020 年12 月,泉州地区共有151 917 例新生儿进行串联质谱遗传代谢病筛查,异戊酰基肉碱(isovalerylcarnitine, AISO-C5 ) 浓度升高的筛查样本应用MassARRAY 技术进行IVD 基因突变筛查,IVA 疑似样本采用高通量测序技术诊断。结果　研究期间共有132 例新生儿表现为浓度升高,采用传统筛查规则需召回132 例新生儿,召回复查阳性人数20 例,1 例确诊为IVA 患者,IVA 的阳性预测值为0.76%。此外,3 例新生儿被诊断为2- 甲基丁酰辅酶A 脱氢酶缺乏症（2-methylbutyryl-CoA dehydrogenase deficiency,2-MBAD）患者。联合应用基因突变筛查后,仅5 例新生儿结果异常,基因诊断证实4 例新生儿为IVA 携带者,1 例新生儿为IVA 患者,因此IVA 的阳性预测值提高至20%。所有患者的新生儿筛查和召回复查结果均显示AISO-C5 浓度升高。1 例IVA 患者携带IVD 基因c.499A > G(p.M167V) 和c.1208A > G（p.Y403C）复合杂合突变,3 例2-MBAD 患者均携带ACADSB 基因c.1165A > G (p.M389V)纯合突变。结论　联合应用MassARRAY 技术进行IVD 基因突变筛查可以有效排除AISO-C5 升高的假阳性标本,提高阳性预测值,明显提高IVA 的新生儿筛查效率。     

儿童3-羟基-3-甲基戊二酸尿症1例的护理

<正>3-羟基-3-甲基戊二酸尿症(3-HMG),又称3-羟基-3-甲基戊二酰辅酶A(HMGCoA)裂解酶缺乏症,为常染色体隐性遗传性有机酸代谢病,是由戊二酰辅酶A脱氢酶(glutaryl—CoAdehydrogenase,GCDH)缺陷所致。GCDH位于线粒体基质,参与色氨酸、赖氨酸和羟赖氨酸在体内的代谢。其缺陷可导致戊二酰辅酶A在线粒体内转化为巴豆酰辅酶A过程受阻,戊二酸、3-     

珠海地区20364例新生儿遗传代谢病筛查结果分析

目的 初步了解并探讨珠海地区新生儿遗传代谢病筛查情况及发病率,为地区性防治出生缺陷提供有效依据。方法 选取2021年1月至2022年12月在珠海地区出生的20 364例新生儿作为研究对象,进行多种遗传代谢病筛查,对初筛阳性者召回复查,复查仍阳性者进行尿质谱分析和基因检测等明确诊断,统计分析初筛阳性率、总发病率等。结果 20 364例接受串联质谱筛查的新生儿中,初筛阳性人数687例,初筛阳性率为3.37%;初筛阳性召回人数621例,初筛阳性召回率为90.39%。经召回复查发现70例可疑阳性,筛查阳性率为0.34%,召回阳性率为11.27%,最终确诊7例,总发病率为1/2 909。其中,氨基酸代谢病2例(希特林蛋白缺乏症和高甲硫氨酸血症各1例)、脂肪酸代谢障碍4例(原发性肉碱缺乏症2例、中链酰基辅酶A脱氢酶缺乏症和极长链酰基辅酶A脱氢酶缺乏症各1例)、有机酸代谢病(甲基丙二酸血症)1例。7例确诊患儿中有6例进行了基因突变检测,并对其主要标志物及相关指标进行分析,其中氨基酸基因确诊2例,脂肪酸基因确诊3例,有机酸基因确诊1例。结论 珠海地区新生儿遗传代谢病总发病率为1/2 909,略低于该地...     

气相色谱-质谱联用技术在遗传代谢性疾病诊断中的应用

目的探讨气相色谱-质谱联用(GC-MS)技术在遗传代谢病诊断中的应用。方法收集5 778例疑似遗传代谢病患儿的尿液,经萃取、衍生后采用GC-MS技术检测132种代谢产物,通过遗传代谢病分析软件并结合实验室其他检测等进行诊断。结果 5 778例疑似患儿尿液样本中有1 100例(19%)有异常代谢产物,共有106例患儿被明确诊断出17种疾病,其中尿液中特征性指标异常的患儿80例、结合血串联质谱结果确诊26例患儿。80例尿液出现特征性指标异常的患儿中有机酸代谢障碍疾病患儿65例,确诊疾病11种;氨基酸代谢障碍疾病患儿15例,确诊疾病3种;包括甲基丙二酸血症33例、高苯丙氨酸血症12例、丙酸血症7例、戊二酸血症Ⅰ型7例、尿素循环障碍6例、β酮硫解酶缺乏症3例、乙基丙二酸血症2例、枫糖浆尿症2例、异戊酸血症2例、多种羧化酶缺乏症2例、酪氨酸血症Ⅰ型1例、2-羟基戊二酸血症1例、3-甲基巴豆酰辅酶A羧化酶缺乏症1例、3-羟基-3-甲基戊二酸尿症1例。结合血串联质谱结果确诊的26例患儿中希特林蛋白缺乏症19例、极长链酰基辅酶A脱氢酶缺乏症5例、中链酰基辅酶A脱氢酶缺乏症2例。结论 GC-MS技术对有机酸代谢异常和部分氨基酸代谢异常诊断有特异性。GC-MS技术检测结果影响因素多,但对疾病最终诊断无影响。     

串联质谱技术在广东省惠州地区新生儿遗传性代谢病筛查中的应用研究

目的探讨串联质谱技术在新生儿遗传性代谢病筛查中的价值。了解广东省惠州地区新生儿遗传性代谢病的发生和基因突变情况。方法应用串联质谱技术(MSMS)对2017年1月至2019年2月该地区的34 689例新生儿进行遗传性代谢病筛查,对阳性者立即召回并监测分析尿中的氨基酸、肉碱、有机酸等代谢产物,应用MSMS对阳性患儿的突变基因进行检测。结果 34 689例新生儿中可疑阳性302例(8.7‰),确诊患儿10例,甲基丙二酸血症2例,戊二酸血症Ⅰ型2例,极长链酰基辅酶A脱氢酶缺乏症1例,短链酰基辅酶A脱氢酶缺乏症1例,苯丙酮尿症2例,精氨酸血症1例,瓜氨酸血症Ⅰ型1例,发病患者所占比例分别为2/34689、2/34 689、1/34 689、1/34 689、2/34 689、1/34 689、1/34 689。结论应用MSMS对惠州地区新生儿遗传代谢病进行筛查,能够起到早发现、早诊断、早治疗的作用,从而有效降低该地区出生人口缺陷,是一种能够有效预防遗传代谢病的途径。     

淄博地区223 368例新生儿遗传代谢病串联质谱法筛查结果分析

目的 分析223 368例淄博地区新生儿遗传代谢病(IMD)串联质谱(MS/MS)法的筛查结果。方法 收集在山东省淄博市妇幼保健院进行IMD筛查的新生儿干血滤纸片223 368例,均于出生后3～7 d采集足跟血,并使用MS/MS法进行IMD筛查。统计淄博地区新生儿IMD筛查阳性率;分析淄博地区新生儿IMD发病类型及基因检测结果;记录淄博地区IMD新生儿的随访结果。结果 确诊IMD患儿75例,发病率为0.034%(75/223 368)。其中,有机酸血症(OAD) 51例,占比最高(0.023%),其次为氨基酸代谢病(AAD) 13例(0.006%)和脂肪酸氧化障碍(FAOD)11例(0.005%)。新生儿IMD中,以甲基丙二酸血症(MMA)、中链酰基辅酶A脱氢酶缺乏症(MCADD)发病率最高。其中OAD中,以MMA为主。AAD中,以高蛋氨酸血症、希特林蛋白缺乏症(NICCD)为主。FAOD中,以MCADD、原发性肉碱吸收障碍(PCD)为主。45例MMA新生儿中,42例接受基因检测。其中40例检出MMACHC基因共22种突变位点,以c.609G>A(29.11%)、c.658＿66...     

非衍生化串联质谱技术筛查上海部分地区新生儿遗传代谢病的回顾性分析

目的回顾性分析用串联质谱技术筛查新生儿遗传代谢病的可行性和新生儿遗传代谢病的发病率。方法用非衍生化串联质谱技术检测2010年至2016年上海部分地区126 579例新生儿滤纸干血片上11种氨基酸、游离肉碱和30种酰基肉碱,对新生儿进行氨基酸代谢异常、有机酸代谢异常和脂肪酸氧化代谢异常三大类疾病筛查。结果 126 579例新生儿中确诊遗传代谢病26例,包括氨基酸代谢异常13例、有机酸代谢异常7例和脂肪酸氧化代谢异常6例,总发病率为1∶4 869;另确诊2例母源性原发性肉碱缺乏症和1例母源性3-甲基巴豆酰辅酶A羧化酶缺乏症。结论非衍生化串联质谱技术可有效用于新生儿遗传代谢病的筛查和诊断,还可对无症状母亲作出诊断。     

一例3-甲基巴豆酰辅酶A羧化酶缺乏症患儿的护理

3-甲基巴豆酰辅酶A羧化酶缺乏症是一种先天性代谢缺陷病,1970年由Eldjarn等[1]首先报道。3-甲基巴豆酰辅酶A羧化酶是亮氨酸中间代谢产物3-甲基巴豆酰辅酶A转化成3-甲基戊烯二酸单酰辅酶A的一个羧化酶,此酶缺乏造成3-甲基巴豆酰辅酶A堆积,继而与甘氨酸结合生成3-甲基巴豆酰甘氨酸,与左旋肉碱结合生成3-羟基异戊酸,使尿中这些有机酸浓度增加,并继发肉碱缺乏。部分患者以严重代谢性酸中毒、低血糖、昏迷等形式急性起病,部分患者则表现为进行性神经系统损害,顽固性皮肤损害是其特征性表现之一,而尿中3-甲基巴豆酰甘氨酸、3-羟基异戊酸浓度明…     

2018-2019年上饶市串联质谱筛查新生儿遗传代谢病情况分析

目的 探讨串联质谱检测在新生儿疾病筛查中的临床应用价值,明确串联质谱筛查在上饶市的初筛阳性率及确诊阳性率,统计出新生儿遗传代谢病在上饶市的总体发病率.方法 回顾性分析2018年10月至2019年8月在上饶市妇幼保健院新生儿筛查中心进行遗传代谢病筛查的15207例新生儿筛查结果;利用串联质谱技术对新生儿血液样本进行氨基酸、有机酸、脂肪酸、游离肉碱和酯酰肉碱谱检测,根据记录不同质荷比的离子质量谱,通过待测样品峰面积与内标峰面积之比获得定量结果,通过线性回归计算出所测样品各项指标的浓度.根据结果分析初筛阳性情况,明确串联质谱筛查在上饶市的初筛阳性率及确诊阳性率,对初筛阳性患儿召回复查后仍为阳性的患儿进行实验室检测分析,观察记录不同遗传代谢病的临床症状,以便早期发现遗传代谢病患儿并及时予以有效治疗,保障儿童正常体格发育及智力发育.结果 诊断出短链酰基辅酶A脱氢酶缺乏症1例,中链酰基辅酶A脱氢酶缺乏症1例,瓜氨酸血症Ⅱ型1例,原发性肉碱缺乏症1例.结论 串联质谱技术应用于新生儿遗传代谢病筛查有利于疾病的早期发现和诊断,兼有超敏性、高特异性、高通量、可重复性的特点,有利于疾病的及早干预.     

Electrospray tandem mass spectrometry for analysis of acylcarnitines in dried postmortem blood specimens collected at autopsy from infants with unexplained cause of death.

BACKGROUND: Deaths from inherited metabolic disorders may remain undiagnosed after postmortem examination and may be classified as sudden infant death syndrome. Tandem mass spectrometry (MS/MS) may reveal disorders of fatty acid oxidation in deaths of previously unknown cause. METHODS: We obtained filter-paper blood from 7058 infants from United States and Canadian Medical Examiners. Acylcarnitine and amino acid profiles were obtained by MS/MS. Specialized interpretation was used to evaluate profiles for disorders of fatty acid, organic acid, and amino acid metabolism. The analyses of postmortem blood specimens were compared with the analyses of bile specimens, newborn blood specimens, and specimens obtained from older infants at risk for metabolic disorders. RESULTS: Results on 66 specimens suggested diagnoses of metabolic disorders. The most frequently detected disorders were medium-chain and very-long-chain acyl-CoA dehydrogenase deficiencies (23 and 9 cases, respectively), glutaric acidemia type I and II deficiencies (3 and 8 cases, respectively), carnitine palmitoyl transferase type II/translocase deficiencies (6 cases), severe carnitine deficiency (4 cases), isovaleric acidemia/2-methylbutyryl-CoA dehydrogenase deficiencies (4 cases), and long-chain hydroxyacyl-CoA dehydrogenase/trifunctional protein deficiencies (4 cases). CONCLUSIONS: Postmortem metabolic screening can explain deaths in infants and children and provide estimates of the number of infant deaths attributable to inborn errors of metabolism. MS/MS is cost-effective for analysis of postmortem specimens and should be considered for routine use by Medical Examiners and pathologists in unexpected/unknown infant and child death.     

Organic acid disorders detected by urine organic acid analysis: twelve cases in Thailand over three-year experience

BACKGROUND: Disorders of organic acid (OA) metabolism are generally detected by qualitative analysis of urine organic acids by gas chromatography/mass spectrometry (GC/MS) which was well established in developed countries since 1980s. Confirmation of the diagnosis of organic acid disorders by OA analysis, enzyme analysis and molecular study is a difficult task in developing countries. METHODS: During 2001-2004, we had analysed 442 urine samples in 365 patients and identified 12 cases of organic acid disorders. RESULTS: We identified the following disorders: alkaptonuria (ALK)=1, isovaleric acidemia (IVA)=3, propionic acidemia (PA)=2, methylmalonic acidemia (MMA)=3, glutaric aciduria, type I (GA-I)=1, multiple carboxylase deficiency (MCD)=1, and glutaric acidemia, type II (GA-II)=1. CONCLUSIONS: OA disorders had never been diagnosed in Thailand before, until GC/MS technology was introduced to Thailand in 2001. Urine OA analysis also provided a diagnostic clue to other inborn errors of metabolism including amino acid disorders, urea cycle disorders, disorders of carbohydrate metabolism, and mitochondrial fatty acid oxidation disorders. Since then, we were able to diagnose numerous disorders, which led to prompt treatment and better outcome in our patients.     

成都市新生儿葡萄糖-6-磷酸脱氢酶缺乏症筛查分析

目的 了解成都地区新生儿葡萄糖-6-磷酸脱氢酶（G6PD）缺乏症的发病分布情况.方法 采用NADP＋氧化还原酶法,对11 085例（男6 440例,女4 645例）就诊患儿进行红细胞中G6PD活性的定量检测.结果 在11 085例受检者中,检出G6PD缺乏者677例,总检出率6.1%.其中男婴545例,占男婴检查人数的8.46%（545/6 440）;女婴132例,占女婴检查人数的2.84%（132/4 645）.结论 成都地区G6PD缺乏症检出率较高,应在新生儿期常规开展G6PD检测,及早诊断,采取有效防范措施,预防由G6PD缺乏引起的新生儿高胆红素血症及核黄疸的发生.     

Glutaric acidemia type II patient with thalassemia minor and novel electron transfer flavoprotein-A gene mutations: A case report and review of literature

Glutaric acidemia type II (GAII), also known as multiple acyl-CoA dehydrogenase deficiency, is an autosomal recessive inborn error of amino acid and fatty acid metabolism. We report a case of GAII with novel electron transfer flavoprotein (ETF)-A mutations in a 2-year-old female with thalassemia minor. The patient developed an episode of hypoglycemia and hypotonicity on the postnatal first day. Laboratory investigations revealed elevations of multiple acyl carnitines indicating glutaric acidemia type II in newborn screening analysis. Urinary organic acids were evaluated for the confirmation and revealed a high glutaric acid excretion. Genetic analysis revealed two novel mutations in the ETF-A gene, which are considered to be compound heterozygote. At the 8 mo of life ketone therapy was added, which significantly increased the neuromotor development. The patient had been closely followed for two years with carnitine, riboflavin, coenzyme Q10, and ketone supplementation in addition to a high carbohydrate diet. Although the patient had comorbidity like thalassemia minor, her neuromotor development was normal for her age and had no major health problems. This specific case expands the previously reported spectrum of this disease.     

梧州市新生儿葡萄糖-6-磷酸脱氢酶缺乏症筛查结果分析

目的 了解梧州市新生儿葡萄糖-6-磷酸脱氢酶(G6PD)缺乏症的筛查情况,为患该病新生儿的防治提供参考依据.方法 采用G6PD定量(连续监测速率法)对3 235例新生儿G6PD活性进行检测,并对筛查结果进行分析.结果 所有被检测的新生儿中G6PD缺乏症的发病率是10.88%,其中男性的发病率为12.21%,女性的发病率为9.33%.结论 梧州市作为G6PD缺乏症的高发区,应常规开展新生儿葡萄糖-6-磷酸脱氢酶缺乏症的筛查工作,对G6PD缺乏症患者及时采取预防性措施,避免因出现核黄疸而造成的智力低下或死亡等后果,确保新生儿的生命质量,从而提高优生优育的水平.     

Excretion of short-chain n-acylglycines in the urine of a patient with D-glyceric acidemia

Five urine samples were collected in clinically quiet periods over a period of one year from a patient suffering from D-glyceric acidemia, and investigated for presence or absence of glycine-conjugates. The findings of isovalerylglycine, 2-methylbutyrylglycine, isobutyrylglycine, and tiglylglycine are interpreted as indications of intracellular accumulations of isovaleryl-CoA, 2-methylbutyryl-CoA and isobutyryl-CoA. Similarly, the findings of elevated amounts of butyric acid and hexanoic acid together with butyrylglycine, hexanoylglycine, and suberic acid suggest intracellular accumulations of straight-chain acyl-CoA's. It is therefore suggested that this child has a common derangement in his acyl-CoA dehydrogenases (in addition to his primary defect).As possible secondary consequences of this, two points can be mentioned: firstly hyperglycinemia, from which the patient suffered, and secondly, diminished tendency to ketosis, a condition from which the child never suffered, not even in connection with severe intercurrent disease.     

高危新生儿遗传代谢病临床病因学分析

目的 初步研究新生儿重症监护室(NICU)先天性遗传代谢病(IEM)高危新生儿的临床病因学.方法 应用气相色谱-质谱联用分析法(GC/MS)对100 例临床IEM 高危新生儿进行新鲜晨尿有机酸分析,并查血常规、肝肾功能、乳酸、丙酮酸、β-羟丁酸、血氨和同型半胱氨酸,其中24 例患儿尿有机酸分析结果阳性,临床拟诊为IEM,对临床拟诊为IEM 的24 例患儿进行1 ～2 个疗程的治疗,之后复查GC/MS 尿有机酸分析.结果 24 例临床拟诊为IEM 的患儿12 例确诊为IEM,其中丙酮酸血症、酪氨酸血症和同型半胱氨酸血症各2 例,甲基丙二酸尿症、戊二酸血症Ⅱ型、乳糖不耐症、高甲硫氨酸血症、β-酮硫解酶缺乏症和鸟氨酸氨甲酰转移酶缺乏症各1 例,均呈常染色体隐性遗传.12 例IEM 患儿的临床表现各不相同,其中血管病变3 例(微血栓形成1 例和脑实质内出血2 例),新生儿惊厥和复发性代谢性酸中毒各2 例,新生儿猝死、难治性低血糖、顽固性腹泻、遗传相关性高胆红素血症和重症肺炎各1 例.12 例IEM 患儿的疾病极期,100%出现高氨血症,83%出现丙酮酸血症,67%出现肾损害和代谢性酸中毒,50%出现肝损害,42%出现血液系统损害.结论 高危新生儿IEM 临床病因复杂,随着新技术的发展,新生儿IEM 疾病谱不断扩大,进一步揭示了高危新生儿病因,为临床诊治提供依据.     

Complementation studies of isovaleric acidemia and glutaric aciduria type II using cultured skin fibroblasts.

Using cultured skin fibroblasts, we studied the heterogeneity of inborn errors of leucine metabolism such as isovaleric acidemia (IVA), glutaric aciduria type II (GA II), and multiple carboxylase deficiency (MC). We first developed a simple macromolecular-labeling test to measure the ability of cells to oxidize [1-14C]isovaleric acid in situ in culture. Cells from two different lines were fused using polyethylene glycol, and the ability of the heterokaryons to oxidize [1-14C]isovaleric acid was tested by the macromolecular-labeling test. The MC line complemented with all 10 IVA lines tested; heterokaryons showed 99 +/- 68% more activity than the unfused mixture of component cells. GA II/IVA heterokaryons exhibited poor growth, but when the culture remained confluent, the GA II cells complemented with all six IVA lines tested, showing a 71 +/- 41% increase in activity. The relatively large standard deviations are due to a few experiments in which significant enhancement of macromolecular-labeling test activity was not observed upon fusion, but significant complementation was clearly observed in repeats of the same combinations. These results are consistent with our previous findings, which indicated that the decreased ability of GA II cells to oxidize isovaleryl-CoA involves a defective electron-transporting system rather than a defective isovaleryl-CoA dehydrogenase. IVA/IVA heterokaryons showed no complementation in any combination tested, indicating no detectable heterogeneity in isovaleric acidemia. This finding indicates that the same gene is mutated in all IVA lines. Previous results indicated that this gene codes for isovaleryl-CoA dehydrogenase.     

2121例新生儿畸变产物耳声发射听力初筛结果分析

目的:分析NICU及产科病房用畸变产物耳声发射进行新生儿听力初筛结果。方法:采用畸变产物耳声发射对1576例NICU及545例产科病房的新生儿进行听力初筛。结果:正常新生儿初筛通过率85.14%,NICU筛查通过率为56.28%。结论:NICU筛查结果受多种因素影响,如疾病、测试环境、性别等。在畸变产物耳声发射筛查中及时认识这些因素,有利于提高筛查成功率。