探讨甲基丙二酸血症(MMA)的临床特征及其被误诊为血液系统疾病的原因，并进行相关文献复习。

选择2016年11月2日及2017年2月25日，于南京医科大学附属妇产医院收治的被误诊为血液系统疾病的2例MMA患儿为研究对象，其年龄分别为5个月与15岁。对这2例MMA患儿的诊疗过程进行回顾性分析。采用基于高通量测序技术的遗传代谢病基因Panel测序法对患儿家系进行致病基因突变分析。本研究遵循的程序符合2013年修订的《世界医学协会赫尔辛基宣言》要求。设定检索策略，以"甲基丙二酸血症""误诊""血常规""MMA"等为关键词，对万方数据库、中国知网等数据库中关于MMA的文献进行检索，设定检索时间为2000年1月1日至2017年12月31日。

①患儿1于出生后1个月时误诊为小细胞低色素性贫血，5个月时确诊为MMA。其血液高效液相色谱-串联质谱检测(HPLC-MS/MS)结果提示，丙酰肉碱(C3)浓度为3.2 μmoL/L，C3/乙酰肉碱(C2)为0.34，C3/游离肉碱(C0)为0.22；尿液气相色谱-质谱法(GC/MS)检测结果提示，尿甲基丙二酸值为20 μg/μmoL肌酐；血清同型半胱氨酸(Hcy)浓度为40 μmol/L。血常规检查结果显示，血红蛋白(Hb)为105 g/L。其基因检测结果提示，基因突变位点为MMACHC c．80G>A/c.609G>A。该例患儿最终被确诊为MMA合并高同型半胱氨酸血症，属于cblC型。②患儿2于出生后6个月误诊为血小板减少，15岁时确诊为MMA。其血液HPLC-MS/MS检查结果提示，C3浓度为7.22 μmo/L，C3/C2为0.32，C3/C0为0.82；尿液GC/MS检测结果提示尿甲基丙二酸值为14.02 μg/μmoL肌酐；血清Hcy浓度为80 μmol/L；血常规检查结果提示Hb为103 g/L，血小板计数为85×10⁹/L。其基因检测结果提示，基因突变位点为MMACHC c．482G>A/c.609G>A。该例患儿最终被确诊为MMA合并高同型半胱氨酸血症，属于cblC型。③2例患儿均被误诊为血液系统疾病并采取输血、给予铁剂和激素等对症治疗，均无明显临床疗效。2例患儿确诊为MMA后，给予羟钴胺肌内注射(1 mg/d)，以及左卡尼汀、甜菜碱、亚叶酸钙口服治疗1个月，复查血常规结果提示各项指标均在正常参考值范围，并且病情稳定。

MMA的临床表现无特异性，部分患儿易误诊为血液系统疾病，血液HPLC-MS/MS、尿液GC/MS和基因检测是诊断MMA的有效方法。

To investigate the clinical characteristics of methylmalonic acidemia (MMA) and review the related literatures, aiming at improving the clinicians′ recognition of MMA.

On November 2, 2016 and February 25, 2017, two children with MMA who were misdiagnosed as hematological diseases were selected as research subjects. The clinical data of this 2 children were collected from Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University. Their ages were 5-month and 15-year old, respectively. A retrospective analysis of the diagnosis and treatment processes of the 2 children with MMA was conducted, and a search strategy was set. The key words were " methylmalonic academia" " misdiagnosis" " blood routine" and " MMA" . Literatures on MMA were searched in Wanfang Database, China National Knowledge Infrastructure (CNKI) Database, etc.. The retrieval period was from January 1, 2000 to December 31, 2017. The genetic metabolic disease gene Panel sequencing based on high-throughput sequencing technology was used to analyze the mutation of the pathogenic gene. This study met the requirements of the World Medical Association Declaration of Helsinki revised in 2013.

①Case 1 was misdiagnosed as small cell hypochromic anemia at 1 month old, and she was diagnosed as MMA at 5 months old. The results of high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) showed that propionylcarnitine (C3) was 3.2 μmoL/L, C3/ acetylcarnitine (C2) was 0.34, C3/free carnitine (C0) was 0.22. The results of urine gas chromatography-mass spectrometry (GC/MS) showed that the urine methylmalonic acid value was 20 μg/μmoL creatinine. The concentration of serum homocysteine (Hcy) was 40 μmol/L. Blood routine examination showed hemoglobin (Hb) was 105 g/L. The results of gene detection indicated that the mutation site of the gene was MMACHC c. 80G>A/c.609G>A. This girl was finally diagnosed as MMA complicated with hyperhomocysteinemia, belonging to cblC type. ② Case 2 was misdiagnosed as thrombocytopenia at 6 months old, and this boy was diagnosed as MMA at the age of 15. HPLC-MS/MS results showed that C3 was 7.22 μmo/L, C3/C2 was 0.32, C3/C0 was 0.82. Urine GC/MS results showed that urine methylmalonic acid was 14.02 μg/μmoL creatinine. Serum Hcy concentration was 80 μmol/L. Blood routine examination showed that Hb was 103 g/L and platelet count was 85×10⁹/L. The results of gene detection indicated that mutation site of the gene was MMACHC c. 482G>A/c.609G>A. This boy was finally diagnosed as MMA complicated with hyperhomocysteinemia, belonging to cblC type. ③The two children were misdiagnosed as hematological diseases and received treatment such as blood transfusion, iron treatment and hormone administration, etc., with no obvious clinical effects. After two children were diagnosed with MMA, they were given intramuscular injection of hydroxycobalamin (1 mg/d) and oral administration of L-carnitine, betaine and calcium folinate for 1 month. The results of blood routine examination showed that all indexes were within the normal reference range and the condition was stable.

The clinical manifestations of MMA are nonspecific, and some children are easily misdiagnosed as blood system diseases. Blood HPLC-MS/MS, urine GC/MS and gene detection are effective methods for diagnosing MMA.