Prenatal diagnosis for methylmalonic acidemia and inborn errors of vitamin B12 metabolism and transport
- 作者：Chantal F. Morel ; David Watkins ; Patrick Scott ; Piero Rinaldo and David S. Rosenblatt
- 关键词：Prenatal diagnosis ; cblA ; cblB ; cblC ; cblE ; cblF ; cblG ; Transcobalamin ; Methylmalonyl CoA mutase ; Methylmalonic acid ; Homocysteine
- 刊名：Molecular Genetics and Metabolism
- 出版年：2005
- 期刊代码：175_10967192
- 类别：bio
- 出版时间：2005
- 卷：86
- 期：1-2
- 页码：160-171
- 文件大小：539 K
摘要
Vitamin B12 (cobalamin) is an essential cofactor for two enzymes: methionine synthase (MS), which requires methylcobalamin (MeCbl), and methylmalonyl-CoA mutase (MUT), which requires adenosylcobalamin (AdoCbl). A number of individually rare inborn errors of cobalamin metabolism are known and are distinguished by complementation analysis (mut, cblA-cblH). From 1984 to 2005, we have performed prenatal diagnosis for 117 high-risk pregnancies. We identified a total of 21 affected pregnancies (18%): cblA, 2/8; cblB, 0/5; cblC, 10/52; cblE, 2/3; cblF, 0/5; cblG, 0/5; transcobalamin deficiency, 0/2; methylmalonyl-CoA mutase (mut) deficiency, 7/30; and unclassified MMA, 0/7. Studies were performed on amniotic fluid, cultured chorionic villus cells (CCVC), cultured amniocytes (CA), or various combinations of these three types of sample. Analyses done include propionate and methyltetrahydrofolate incorporation into protein and cobalamin cofactor levels (CA: 92%, CCVC: 18%), amniotic fluid metabolite measurement either by gas chromatography/mass spectrometry (GC/MS) or by liquid chromatography–tandem mass spectrometry (LC–MS/MS) (49%), and direct mutation analysis (5%). There was one false negative CCVC result in a pregnancy at risk for cblC and one false positive CCVC in a pregnancy at risk for mutase deficiency. One unaffected pregnancy at risk for an unclassified form of MMA and another unaffected pregnancy at risk for cblC, had higher than control MMA amniotic fluid levels. Our experience suggests that prenatal diagnosis for these disorders should be done by application of two independent methods, and that CA studies appear more reliable than CCVC studies.