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中华妇幼临床医学杂志(电子版) ›› 2017, Vol. 13 ›› Issue (01) : 39 -45. doi: 10.3877/cma.j.issn.1673-5250.2017.01.007

所属专题: 文献

论著

母亲维生素B12缺乏与婴儿继发性甲基丙二酸尿症
吴桐菲1, 丁圆2, 李溪远2, 刘玉鹏2, 李东晓2, 宋金青2, 李梦秋3, 王翔3, 赵子江3, 秦亚萍3, 杨艳玲2,()   
  1. 1. 100069 北京,首都医科大学临床检验中心
    2. 100034 北京大学第一医院儿科
    3. 100070 北京福佑龙惠遗传病专科门诊部
  • 收稿日期:2016-09-13 修回日期:2017-01-05 出版日期:2017-02-01
  • 通信作者: 杨艳玲

Maternal vitamin B12 deficiency and infants with secondary methylmalonic aciduria

Tongfei Wu1, Yuan Ding2, Xiyuan Li2, Yupeng Liu2, Dongxiao Li2, Jinqing Song2, Mengqiu Li3, Xiang Wang3, Zijiang Zhao3, Yaping Qin3, Yanling Yang2,()   

  1. 1. Clinical Laboratory Center, Capital Medical University, Beijing 100069, China
    2. Department of Pediatrics, Peking University First Hospital, Beijing 100034, China
    3. Beijing Fuyoulonghui Hereditary Disease Specialist Clinics, Beijing 100070, China
  • Received:2016-09-13 Revised:2017-01-05 Published:2017-02-01
  • Corresponding author: Yanling Yang
  • About author:
    Corresponding author: Yang Yanling, Email:
引用本文:

吴桐菲, 丁圆, 李溪远, 刘玉鹏, 李东晓, 宋金青, 李梦秋, 王翔, 赵子江, 秦亚萍, 杨艳玲. 母亲维生素B12缺乏与婴儿继发性甲基丙二酸尿症[J]. 中华妇幼临床医学杂志(电子版), 2017, 13(01): 39-45.

Tongfei Wu, Yuan Ding, Xiyuan Li, Yupeng Liu, Dongxiao Li, Jinqing Song, Mengqiu Li, Xiang Wang, Zijiang Zhao, Yaping Qin, Yanling Yang. Maternal vitamin B12 deficiency and infants with secondary methylmalonic aciduria[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2017, 13(01): 39-45.

目的

探讨母亲维生素B12缺乏导致的婴儿继发性甲基丙二酸尿症(MMA)的临床特点,以及该病的诊断、治疗及转归。

方法

选择2014年11月12日,因"吐奶、贫血、疑为遗传性MMA" ,于北京大学第一医院被确诊为因母亲维生素B12缺乏导致的继发性MMA、日龄为27 d的男性双胎新生儿为研究对象。对双胎患儿及其母亲进行血常规、血清维生素B12与叶酸检测,以及血清与尿液总同型半胱氨酸检测,尿液有机酸谱及血液氨基酸、肉碱谱检测,同时检测患儿及其父母的MMA相关基因突变情况。本研究与2例受试者监护人签署临床研究知情同意书,本研究遵循的程序通过北京大学第一医院医学伦理委员会的审核批准。

结果

①2例患儿生后4 d于当地医院就诊时,尿液甲基丙二酸浓度分别为479.21 mmol/mol肌酐和65.90 mmol/mol肌酐(正常参考值为0.20~3.60 mmol/mol肌酐);血液丙酰肉碱浓度分别为12.01 μmol/L和10.55 μmol/L(正常参考值为1.00~5.00 μmol/L)。生后27 d于北京大学第一医院就诊时发现,2例患儿均存在中度贫血,长子血清总同型半胱氨酸浓度轻度增高,为17.6 μmol/L(正常参考值为0~15.0 μmol/L),次子正常,为14.3 μmol/L;血清维生素B12浓度均降低,分别为121.0 pmol/L与105.0 pmol/L(正常参考值为133.0~675.0 pmol/L);血清叶酸浓度均正常,分别为26.50 nmol/L与18.60 nmol/L(正常参考值为>6.80 nmol/L);尿液中均未检出甲基丙二酸,血液丙酰肉碱均增高,分别为9.26 μmol/L与15.90 μmol/L。给予维生素B12肌内注射,口服亚叶酸钙及左卡尼汀治疗后,2例患儿尿液中均未检出甲基丙二酸,血液丙酰肉碱浓度恢复正常,智力、运动发育正常,贫血好转。②2例患儿母亲于早孕期出现厌食、呕吐等早孕期妊娠反应,中孕期出现糖尿病、甲状腺功能减低、大细胞性贫血及同型半胱氨酸血症,曾口服补血中药及铁剂治疗,未曾补充维生素B12治疗。产后2个月时,母亲血清维生素B12浓度降低,血清总同型半胱氨酸浓度升高。经左卡尼汀、甲钴胺、叶酸等营养干预治疗2个月后,母亲血清维生素B12及总同型半胱氨酸浓度均恢复正常。③对于与遗传性MMA相关基因的检测结果显示,2例患儿及其父母均未见MUTMMAAMMABMMACHC等基因突变。

结论

母亲孕期营养不良及健康状况不佳,可导致维生素B12缺乏,继而引起婴儿继发性MMA。临床注意对继发性MMA患者与遗传性MMA的早期鉴别诊断,并于确诊后及时给予维生素B12治疗,是救治继发性MMA,改善其预后的关键。对于妊娠期贫血的母亲,更应注意维生素B12缺乏的可能性,以免导致婴儿罹患继发性MMA。

Objective

To explore the clinical features, diagnosis, treatment and prognosis of twins boys with secondary methylmalonic aciduria (MMA) due to maternal vitamin B12 deficiency.

Methods

On November 12, 2014, the twins boys in 27 days old with secondary MMA due to maternal vitamin B12 deficiency in Peking University First Hospital were selected as research objects. The chief complaint was" vomiting milk and anemia, suspected diagnosis of inherited MMA" . Routine blood, serum vitamin B12 and folic acid test, serum and urine total homocysteine detection, urine organic acids spectrum, blood amino acids and carnitine spectrum detection of the two twins patients and their mother were applied for the differential diagnosis. Meanwhile, mutations in MMA related gene of the two twins patients and their parents were detected. The twins patients′ parents signed the informed consents and this study was approved by the Ethical Review Board of Investigation in Human Being of Peking University First Hospital.

Results

①In 4 days old, the urine methylmalonic acid concentrations of 2 cases of twins boys were 479.21 mmol/mol creatinine and 65.90 mmol/mol creatinine, respectively (normal reference value was 0.20-3.60 mmol/mol creatinine), and the concentrations of blood propionyl-carnitine were 12.01 μmol/L and 10.55 μmol/L, respectively (normal reference value was 1.00-5.00 μmol/L) in the local hospital. Both the twins boys were with moderate anemia when they visited Peking University First Hospital in 27 days old. And serum homocystine concentration in the elder boy was mild elevated which was 17.6 μmol/L (normal reference value was 0-15.0 μmol/L), while serum homocystine concentration in the younger boy was normal which was 14.3 μmol/L. Both the serum vitamin B12 concentrations decreased which were 121.0 pmol/L and 105.0 pmol/L, respectively (normal reference value was 133.0-675.0 pmol/L). Both the serum folic acid concentrations were normal which were 26.5 nmol/L and 18.60 nmol/L, respectively (normal reference value was >6.80 nmol/L). Methylmalonic acid was not detected in their urine, and concentrations of blood propionyl-carnitine increased which were 9.26 μmol/L and 15.90 μmol/L, respectively. Vitamin B12 intramuscular injection, normal diet with the supplements of calcium folinate and levocarnitine by oral had been initialed. After two months of treatment, urine methylmalonic acid was not found and blood propionyl-carnitine concentrations decreased to normal. And the twins were with normal intelligence and motor development. The anemia were improved. ②The mother of the twins manifested morning sickness with pregnancy anorexia and emesis. She had diabetes, hypothyroidism, megaloblastic anemia and homocysteinemia at mid trimester of pregnancy. Although she had taken some traditional Chinese medicine and chalybeate, vitamin B12 was not supplemented. Vitamin B12 deficiency and homocysteinemia were found two months postpartum. After the treatment of levocarnitine, mecobalamin and folic acid, her serum vitamin B12 and homocystine concentrations returned normal four months postpartum. ③Gene analysis of associated inherited MMA revealed that MUT, MMAA, MMAB, MMACHC gene mutation were no found in the twins and their parents.

Conclusions

Prenatal malnutrition and poor health in the mother could lead to the deficiency of vitamin B12,which in turn cause baby′s secondary MMA. Early differential diagnosis of inherited or secondary MMA and vitamin B12 supplements in time are crucial to treat and improve the prognosis of secondary MMA. For the pregnant woman with anemia, vitamin B12 deficiency should be paid attention, in order to avoid second MMA in infants.

表1 继发性甲基丙二酸尿症双胎患儿不同时间点的体格检查及血液、尿液相关项目检查结果
表2 继发性甲基丙二酸尿症双胎患儿母亲不同时间点的血液、尿液相关项目检查结果
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