Methylmalonic acid prenatal diagnosis

Prenatal diagnosis of the disorder may be made (A15). Mothers carrying an affected fetus excrete large quantities of methylmalonic acid. Free methylmalonic acid is also present in the amniotic fluid and cultures of the am-niotic cells enable the nature of the defect to be determined. In the vitamin B12-responsive disorder, treatment of the mother with large doses of vitamin B12 was found to reduce the maternal excretion of methylmalonic acid. 

Figure 55-2 Multi-analyte approach to the prenatal diagnosis of methylmalonic acidemia (cb/C complementation group) by metabolite analysis in ceil-free supernatant of amniotic fluid collected at 16 weeks of gestational age. The symbol marks internal standards. A, Determination of total homocysteine by LC-MS/MS (selected reaction monitoring, SRM, transition m/z 136 to m/z 90 and m/z 140 to m/z 94 for the d -labeled internal standard). The concentration of total homocysteine was l5.7pmol/L (0.7 to 2.0pmol/L). B, Determination of methylmalonic acid by LC-MS/MS (SRM, transition m/z 231 to m/z 119 and m/z 234 to m/z 122 for the d3-labeled internal standard). The concentration of methylmalonic acid was 8.7pmol/L, the reference interval for 16 to 19 weeks of gestational age is 0.2 to 0.7)j,mol/L. C, Determination of propionylcarnitine by LC-MS/MS (parent of m/z 85 scan, the [M+H] ion of C3 is m/z 274, m/z 277 for the interna standard). The concentration was 5.6pmol/L (i.5 to l.8pmoi/L),the C3/C4 ratio was 6.9 (0.9 to 2.6).

Microdetermination of Methylmalonic Acid and Other Short-Chain Dicarb-oxylic Acids by Gas Chromatography Use of Prenatal Diagnosis of Methylmalonic Acidaemia and in Studies of Isovaleric Acidaemia Clin. Chim. Acta 68(2) 127-140 (1976) CA 85 1974n... 

Nakamura, E., Rosenberg, L.E. and Tanaka, K. (1976), Microdetermination of methylmalonic acid and other short chain dicarboxylic acids by gas chromatography Use in prenatal diagnosis of methylmalonic acidemia and in studies of isovaleric acidemia. Clin. Chim. Actay 68,127. 

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