Chemical prenatal diagnosis for inherited organic acidemia

采用稳定同位素稀释法对丙酸血症、甲基丙二酸血症等遗传性有机酸血症进行产前诊断。建立羊水和母体尿液中柠檬酸甲酯和丙二酸甲酯的正常值。对16例甲基丙二酸血症高危胎儿(13例)和丙酸血症高危胎儿(3例)进行产前诊断。3例胎儿诊断为甲基丙二酸血症，1例诊断为丙酸血症。上述诊断与酶活性、生后尿有机酸分析及临床表现相一致。我们还将测量样本的羊水量减少到2毫升。我们还进行了一名患者的产前治疗维生素B_12&gt；反应性甲基丙二酸血症在妊娠的最后10天与口服维生素B_1；12&gt；。在这种情况下，监测母亲尿液中的甲基丙二酸是判断治疗效果的一个有用的指标。通过母亲尿液进行产前诊断将在(1)母亲没有注意到怀孕，(2)母亲从不想进行羊膜穿刺术，(3)母亲错过了合适的羊膜穿刺期，(4)羊膜穿刺术结果不可靠，(5)对先前结果的再次确认。稳定同位素稀释法将适用于有机酸的其他遗传性疾病。

We have studied the prenatal diagnosis for inherited organic acidemia such as propionic acidemia and methylmalonic acidemia using stable isotope dilution method. We established the normal value of methylcitrate and methylmalonate in amniotic fluid and maternal urine. Sixteen fetus at risk for methylmalonic acidemia (n=13) and propionic acidemia (n=3) were diagnosed prenatally. Three fetuses were diagnosed as methylmalonic acidemia and one as propionic acidemia. The above diagnosis was compatible with the results of enzyme activity, postnatal urinary organic acid analysis, and clinical findings. We also minimized the volume of amniotic fluid for measuring sample to 2ml. We also performed the prenatal therapy of a patient with vitamin B_<12> responsive methylmalonic acidemia during the last ten days of gestation with oral administration of vitamin B_<12>. In such occasion, monitoring of methylmalonic acid in maternal urines was an useful indicator for the efficacy of the treatment.Prenatal diagnosis by maternal urine will be indicated in (1) mother did not notice the pregnancy, (2) mother never wants amniocentesis, (3) mother missed suitable period for amniocentesis, (4) unreliable result of amniocentesis, and (5) reconfirmation of the former results. Stable isotope dilution method will be applicable for other inherited disorders of organic acid.