甲基丙二酸血症二例

例1　男,生后5天。因呼吸急促2天,拒乳,昏睡,疑为“新生儿败血症”入院。查体:T353℃,R36次分。反应低下,哭声无力,面色青紫,三凹征阳性,肝肋下15cm,肌张力增强,以下肢为重。母乳喂养。其母孕期正常,无类似家族史。实验室检查:血、尿常规正常。血钙、磷、钠及碱性磷酸酶正...     

新生儿甲基丙二酸血症误诊一例分析

病例：男,7天,因皮肤黄染4天,反应差、发热3天,抽搐昏迷1天入院。患儿出生后第3天出现皮肤黄染。第4天患儿出现发热,反应差,嗜睡,进奶减少。立即到当地医院诊治,予抗感染等处理,病情无好转。     

甲基丙二酸血症cblA型12例分析

目的探讨甲基丙二酸血症(methylmalonic acidemia,MM A)cblA型患儿的临床特点、基因变异类型及治疗效果。方法分析12例cblA型MMA患儿的临床表现,治疗方案及预后,对先证者及其父母进行MMAA基因的变异分析。结果MMA cblA型患儿主要表现为呕吐、气促和嗜睡。维生素B12治疗对11例(91.7%)患儿有效。治疗后患儿血丙酰肉碱、丙酰肉碱与乙酰肉碱比值、尿甲基丙二酸及甲基枸椽酸水平均显著降低,差异有统计学意义(均P<0.05)。8例患儿生长发育正常(66.7%),4例智力运动发育落后(33.3%)。检测到14种MMAA基因变异,包括6种新变异:c.54delA(p.A19Hfs*43)、c.275G>A(p.G92V)、c.456delT(p.G153Vfs*8)、c.667dupA(p.T223Nfs*4)、c.1114C>T(p.Q372X)和c.1137_1138delCA(p.F379Lfs*27)e最常见的变异为c・365T>C(p.L122P)(29.2%)。结论cblA型MMA患儿主要表现为呕吐、气促和嗜睡,大部分患儿为维生素B12治疗有效型。c.365T>C为中国MMAA基因的常见变异。     

甲基丙二酸血症一例

患儿　男 ,出生 9个月 ,以感冒样症状伴吃奶差 1 0天 ,发热、呼吸困难半天、呻吟、嗜睡、软瘫 2小时为主诉入住 ICU病房。父母非近亲结婚。患儿系足月第 1胎顺产 ,无窒息史 ,混合喂养。至今不会坐、爬、站 ,四肢发作性软瘫 ,有时可依学步车行走 ,有时卧床不能活动。呼吸快 ,时常喘息。入院时查体 :体温37.3℃ ,脉搏 1 78次 /分 ,呼吸 5 7次 /分 ,血压 85 / 5 0 mm Hg,一般状态差 ,嗜睡状态 ,呻吟不止 ,呼吸深长 ,出气凉 ,面色苍白全身未见皮疹 ,浅表淋巴结不大 ,囟门平软 ,无颈强 ,心肺正常 ,腹软不胀 ,肝脏右肋下 2 .5 cm,质韧 ,脾未及。…     

先天性甲基丙二酸血症一例

患儿女，生后4天。孕40^＋3周，剖宫产产出，出生体重2650g，孕期及生产史无特殊。生后2天家属反应患儿“进食不理想、睡眠时间长”。生后3天“偶有不自主点头动作”（事后推测为抽泣样呼吸），经查体无明显异常发现，予辅助加强喂养，并在当日患儿吃奶中突然出现口唇发绀，伴有阵发性呼吸急促，哭声无力，持续约2～3min后自行缓解。此后患儿一直嗜睡，偶有抽泣样吸气动作，无主动进食欲望。不久患儿出现体温偏低，给予保暖措施后改善不理想。生后天，患儿呕吐奶汁1次，呼吸急促加重，3h后，患儿突然出现口唇及四肢皮肤紫绀，面色苍白，刺激后无反应，立即给予吸氧等处理后迅速转入我科。     

甲基丙二酸血症串联质谱敏感指标分析

目的 通过分析甲基丙二酸血症(MMA)串联质谱的异常敏感指标结果,为MMA的筛查和诊断提供更好的依据.方法 回顾性分析2016-2019年于北京新筛中心确诊的MMA患儿的串联质谱结果,了解该疾病相关的检测指标及其各指标的敏感度.结果 在筛查的63858名新生儿中,共确诊6例MMA患儿,发病率为1/10643.指标中丙酰...     

东营市111004例新生儿甲基丙二酸血症筛查及诊治分析

目的 回顾性分析本地区新生儿甲基丙二酸血症(MMA)筛查情况,探讨本地区新生儿MMA发病率、诊治情况,以总结经验,指导工作.方法 选择本地区出生48 h后经充分哺乳的新生儿,采足跟血片,应用串联质谱技术检测血片游离肉碱和酰基肉碱水平,可疑阳性新生儿进行尿有机酸分析、血同型半胱氨酸、血生化及基因检测等以明确诊断.结果 本...     

新生儿甲基丙二酸血症2例临床病例分析

目的 探讨2例新生儿甲基丙二酸血症（MMA）的临床特点和诊疗过程。方法 回顾性分析临床资料,进行遗传代谢病血筛和尿筛,并完善基因检测。结果 两名患儿首发症状均为纳差、反应及精神差,且合并有多系统损害,血筛及尿筛显示甲基丙二酸血症,其中一例检测出致病基因,遗传自父母;另一例未检测出明确致病基因。结论 甲基丙二酸血症的临床表现多样化,容易误诊,新生儿串联质谱筛查可及早发现,基因测序有利于明确具体分型,早期诊断对本病的治疗和预后具有重要意义。     

甲基丙二酸血症患儿MUT基因突变分析

目的 检测甲基丙二酸血症(methylmalonic acidemia,MMA)患儿MUT基因突变类型及突变频率,探讨基因型与临床表型之间的关系.方法 依据串联质谱检测血酰基肉碱、气相色谱-质谱检测尿甲基丙二酸以及维生素B_(12)负荷试验等,诊断21例单纯MMA患儿;采用聚合酶链反应和直接测序法对这些患儿进行MUT基因突变检测分析.结果 在21例单纯MMA患儿中14例检测到17种MUT基因突变,其中8种为未报道突变.以c.323G>A(R108H)、c.729_730insTT(D244LfsX39)与c.1630_1631GG>TA(G544X)较为常见,突变频率分别为14.3%、10.7%及14.3%,以错义突变多见(64.7%).14例MUT突变患儿中10例为早发型,1例为迟发型,3例由新生儿出生筛查检出;11例为维生素B_(12)无效型,3例为有效型.结论 揭示了中国MMA患儿中MUT基因的部分突变谱,MUT基因突变患儿发病较早,多为维生素B_(12)无效型.     

4例以血细胞减少发病的早发型甲基丙二酸血症

目的 分析4例以血细胞减少为主的甲基丙二酸血症（MMA）的临床特点,提高基层医生对该病的早期识别及临床诊治水平。方法 回顾性分析2019年2月至2021年5月甘肃省妇幼保健院PICU收治的4例以血细胞减少为主要表现的MMA患儿临床资料。结果 4例患儿首发症状均为血细胞减少,经基因检测明确诊断为MMA,临床表现以喂养困难、精神欠佳、反复感染为主。血丙酰肉碱、丙酰肉碱/乙酰肉碱、丙酰肉碱/游离肉碱及尿甲基丙二酸、甲基枸橼酸水平除1例未检测外其余均升高。基因检测提示均为MMACHC基因复合杂合变异,检出的5种变异位点中c.445T>C变异位点未见文献报道,其余4种为已知致病变异。4例患儿中3例患儿死亡,1例患儿经治疗后症状好转,但存在运动发育迟缓。结论 以血细胞减少发病的早发型MMA,临床表现复杂,容易误诊。对于这类疾病,应提高认识,早诊断,早治疗,从而改善患儿预后。     

Spectrum of bone marrow pathology and hematological abnormalities in methylmalonic acidemia

Patients with isolated methylmalonic acidemia (MMA) may present with a wide range of hematological complications including anemia, leukopenia, thrombocytopenia, and pancytopenia. However, there are very limited data on the development of hemophagocytosis or myelodysplasia in these patients. We report three patients with isolated MUT related MMA who presented with severe refractory pancytopenia during acute illness. Their bone marrow examination revealed a wide spectrum of pathology varying from bone marrow hypoplasia, hemophagocytosis to myelodysplasia with ring sideroblasts. We discuss their management and outcome. This report emphasizes the need for bone marrow examination in these patients with refractory or unexplained severe cytopenia, to confirm bone marrow pathology, and to rule out other diseases with similar clinical presentation for a better clinical outcome.

     

Methylmalonic acidemia mimicking diabetic ketoacidosis and septic shock in infants

Methylmalonic acidemia (MMA) is most common inherited type of organic acidemia. It has diverse presentation in older infants without any initial apparent symptoms. MMA sometimes present with sudden metabolic decompensation, which may mimics common emergencies like septic shock and diabetic ketoacidosis (DKA) without early recognition can be fatal. In born error of metabolism especially organic acidemia should be suspected in any infant presented with severe high anion gap metabolic acidosis. We report two cases of MMA in infants presented acutely mimicking DKA and septic shock.     

脑微损伤的影像学进展

脑微损伤是创伤性脑损伤最常见的类型,然而,其潜在的神经生理机制尚未完全阐明,影响患者的早期诊断、治疗及预后评估。近年来,多项磁共振（MRI）新技术不断地涌现并用于评估脑微损伤,如功能磁共振、灌注MRI、弥散张量成像、定量易感性图谱、T2 mapping等。本研究综述了多模态MRI在脑微损伤中的应用,从不同的角度深入地了解脑微损伤的神经病理机制,有助于提高临床医生对脑微损伤的诊断和治疗。     

Elevated methylmalonic acidemia (MMA) screening markers in Hispanic and preterm newborns

Analysis of California newborn screening (NBS) data revealed a high prevalence of Hispanic infants testing positive for methylmalonic acidemia (MMA), a trend seen for both true- and false-positive cases. Here we show that Hispanic infants have significantly higher levels of MMA screening markers than non-Hispanics. Preterm birth and increased birth weight were found to be associated with elevated MMA marker levels but could not entirely explain these differences. While the preterm birth rate was higher in Blacks than Hispanics, Black infants had on average the lowest MMA marker levels. Preterm birth was associated with lower birth weight and increased MMA marker levels suggesting that gestational age is the stronger predictive covariate compared to birth weight. These findings could help explain why MMA false-positive results are more likely in Hispanic than in Black infants, which could inform screening and diagnostic procedures for MMA and potentially other disorders in newborns.     

Clinical and molecular findings in 37 Turkish patients with isolated methylmalonic acidemia

Background/aim Isolated methylmalonic acidemia (MMA) is caused by complete or partial deficiency of the enzyme methylmalonyl-CoA mutase (mut0 or mut– enzymatic subtype), a defect of its cofactor adenosyl-cobalamin (cblA, cblB, or cblD-MMA), or deficiency of the enzyme methylmalonyl-CoA epimerase. While onset of the disease ranges from the neonatal period to adulthood, most cases present with lethargy, vomiting and ketoacidosis in the early infancy. Major secondary complications are; growth failure, developmental delay, interstitial nephritis with progressive renal failure, basal ganglia injury and cardiomyopathy. We aimed to demonstrate clinical and molecular findings based on long-term follow up in our patient cohort. Materials and methods The study includes 37 Turkish patients with isolated MMA who were followed up for long term complications 1 to 14 years. All patients were followed up regularly with clinical, biochemical and dietary monitoring to determine long term complications. Next Generation Sequencing technique was used for mutation screening in five disease-causing genes including; MUT , MMAA , MMAB , MMADHC , MCEE genes. Mutation screening identified 30 different types of mutations. Results While 28 of these mutations were previously reported, one novel MMAA mutation p.H382Pfs*24 (c.1145delA) and one novel MUT mutation IVS3+1G>T(c.752+1G>T) has been reported. The most common clinical complications were growth retardation, renal involvement, mental motor retardation and developmental delay. Furthermore, one of our patients developed cardiomyopathy, another one died because of hepatic failure and one presented with lactic acidosis after linezolid exposure. Conclusion We have detected two novel mutations, including one splice-site mutation in the MUT gene and one frame shift mutation in the MMAA gene in 37 Turkish patients. We confirm the genotype-phenotype correlation in the study population according to the long-term complications.     

Molecular basis of methylmalonyl-CoA mutase apoenzyme defect in 40 European patients affected by mut(o) and mut- forms of methylmalonic acidemia: identification of 29 novel mutations in the MUT gene

Methylmalonyl-CoA mutase (MCM) apoenzyme deficiency is a rare metabolic disease that may result in distinct biochemical phenotypes of methylmalonic acidemia (MMA), namely mut(o) and mut-. We analyzed a cohort of 40 MCM-deficient patients with MMA affected by either the mut(o) or the mut- form of the disease. By direct sequencing of cDNA and gDNA of the MUT gene, we detected 42 mutations, 29 of which were novel mutations. These included five frameshift mutations (insertion, deletion, or duplication of a single nucleotide), five sequence modifications in consensus splice sites, six nonsense and 12 missense mutations, and a large genomic deletion including exon 12. We explored how the 12 novel missense mutations might cause the observed phenotype by mapping them onto a three-dimensional model of the human MCM generated by homology with the P. shermanii enzyme. In this work we update the spectrum of MCM mutations (n=84), and then discuss their prevalence and distribution throughout the coding sequence in relation to the enzyme structure.     

Mutations in mut methylmalonic acidemia: Clinical and enzymatic correlations

Mut methylmalonic acidemia is caused by mutations in the MUT locus encoding the enzyme methylmalonyl CoA mutase. Genotypic and phenotypic variability in this disease has been studied extensively by biochemical and somatic cell genetic techniques, by molecular cloning, and by gene transfer. Mutations have been identified that cause classic mut^o phenotypes in which there is no detectable enzymatic activity, mut⁻ phenotypes in which there is residual cobalamin-dependent activity, as well as a subset within both mut^o and mut⁻ phenotypes that exhibit interallelic complementation. These mutations illustrate the position, structure, and function of critical domains within this cobalamin-binding enzyme and provide new insights into the biochemical and clinical consequences of enzyme deficiency. © 1997 Wiley-Liss, Inc.