title: Prenatal diagnosis of methylmalonic aciduria by analysis of organic acids and total homocysteine in amniotic fluid.
abstract: BACKGROUND
  Methylmalonic aciduria (MMA) is the most frequent disease of organic aciduria in China. Various biochemical strategies are followed for the prenatal diagnosis of MMA. However, since fetuses affected by MMA have decreased excretion of methylmalonic acid, the difficulties of prenatal biochemical diagnosis are obvious. Gas chromatography mass spectrometry (GC/MS) and tandem mass spectrometry (ESI/MS/MS) have allowed us to identify the disease in affected fetuses. The aim of this study was to determine the value of analysis of organic acids and total homocysteine in amniotic fluid in prenatal diagnosis of MMA.
  
  
  METHODS
  The clinical diagnoses and outcomes of nine probands with MMA and the prenatal diagnoses based on biochemical analysis of nine fetuses at risk for MMA were investigated. Amniotic fluid samples from pregnancies at risk for MMA and metabolically normal pregnancies were obtained at 16 - 24 weeks of gestation. Methylmalonic acid and methylcitric acid were measured by GC/MS, propionylcarnitine was analyzed by ESI/MS/MS, and total homocysteine was determined by fluorescence polarization immunoassay.
  
  
  RESULTS
  In two pregnancies, high levels of methylmalonic acid, methylcitric acid, propionylcarnitine, and total homocysteine indicated combined MMA and homocysteinemia in the fetuses. One of the mothers continued pregnancy and received cobalamin supplement as prenatal treatment, and the other terminated her pregnancy. In one pregnancy, significantly elevated levels of methylmalonic acid, methylcitric acid, and propionylcarnitine, and normal level of total homocysteine was found indicating isolated MMA in the fetus; abortion was performed on this case. In the other six pregnancies, all the levels of the above mentioned metabolites were normal suggesting that the fetuses were not affected by MMA. The diagnoses were confirmed after delivery by testing urinary organic acids and plasma total homocysteine.
  
  
  CONCLUSIONS
  The metabolic abnormalities of MMA occur early in gestation. The level of total homocysteine in amniotic fluid may be an additional indicator of fetal combined MMA and homocysteinemia. Determination of total homocysteine level in amniotic fluid may become a convenient and reliable method for prenatal diagnosis of the disease.
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yan-ling
authors.initials: YL
authors.lastname: Yang
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: Seiji
authors.initials: S
authors.lastname: Yamaguchi
authors.forename: Chun-yan
authors.initials: CY
authors.lastname: Shi
authors.forename: Jin-qing
authors.initials: JQ
authors.lastname: Song
authors.forename: Sujan
authors.initials: S
authors.lastname: Sayami
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.forename: Rong
authors.initials: R
authors.lastname: Yan
authors.forename: Jin-hua
authors.initials: JH
authors.lastname: Dong
authors.forename: Jiong
authors.initials: J
authors.lastname: Qin
mesh_terms: D000653:Amniotic Fluid / Q000737:chemistry*; D002331:Carnitine / Q000031:analogs & derivatives / Q000032:analysis; D002951:Citrates / Q000032:analysis; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006710:Homocysteine / Q000032:analysis* / Q000097:blood; D006801:Humans; D008297:Male; D008764:Methylmalonic Acid / Q000652:urine*; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D002951:Citrates; D006710:Homocysteine; C003223:propionylcarnitine; C031605:2-methylcitric acid; D008764:Methylmalonic Acid; D002331:Carnitine