Chemical prenatal diagnosis for inherited organic acidemia

本文应用稳定同位素稀释法对丙酸血症和甲基丙二酸血症等遗传性有机酸血症进行了产前诊断研究。我们建立了羊水和孕妇尿液中柠檬酸甲酯和丙二酸甲酯的正常值。16个胎儿在产前被诊断为甲基丙二酸血症（n=13）和丙酸血症（n=3）的风险。三名胎儿被诊断为甲基丙二酸血症，一名胎儿被诊断为丙酸血症。上述诊断与酶活性、生后尿有机酸分析结果及临床表现相符。我们还将测量样品的羊水体积减少到2ml。我们还进行了产前治疗的病人与维生素B_<12>反应的甲基丙二酸血症在怀孕的最后十天口服维生素B_<12>。在这种情况下，监测母亲尿液中的甲基丙二酸是治疗效果的有用指标，通过母亲尿液进行产前诊断将表明：（1）母亲没有注意到怀孕，（2）母亲不想进行穿刺，（3）母亲错过了穿刺的合适时期，（4）穿刺结果不可靠，（5）再次确认以前的结果。稳定同位素稀释法也适用于其他有机酸遗传性疾病。

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.