Prenatal diagnosis of the organic acidurias

Abstract

Prenatal diagnosis for the genetic counselling of families at risk for having children with the life-threatening organic acidurias is advancing rapidly. The two major approaches to prenatal diagnosis are the assay for deficient activity of the enzymes in cultured amniocytes and the measurement of increased concentrations of the organic acids in the amniotic fluid. The latter, when done by stable isotope dilution analysis, is rapid, relatively inexpensive and very reliable.

Accumulation of Odd-Numbered Long-Chain Fatty Acids in Fetuses and Neonates with Inherited Disorders of Propionate Metabolism

“…This results in the formation of large amounts of propionyl-CoA in the tissues, which under the highly anabolic conditions of fetal life augments OLCFA production and incorporation into newly synthesized lipids. The fact that part of propionyl-CoA is eliminated from the fetus as propionate derivatives offers the possibility of prenatal diagnosis of PA and MMA by means of the determination of methylcitric acid in amniotic fluid (12). Another class of propionyl-CoA-derived compounds found in amniotic fluids of fetuses with PA and MMA are methyl-branched dicarboxylic acids (I 3).…”

Prenatal Diagnosis and Neonatal Monitoring of a Fetus with Glutaric Aciduria Type II Due to Electron Transfer Flavoprotein (β-Subunit) Deficiency

“…The organic acid analysis of amniotic fluid using such a method (2) was also used for the prenatal diagnosis of our case. Prenatal diagnosis of GAII by the organic acid analysis of amniotic fluid has been reported in several cases in which the propositus was likely to belong to the neonatal onset form of GAII (8)(9)(10)(11)(12)(13)(14). The levels of glutarate and 2-hydroxyglutarate in the amniotic fluid from the affected fetus were about 20 and 3 times those in the normal controls, respectively, in the report by Boue el al.…”

“…Subsequently, his parents had another pregnancy and consulted for the prenatal diagnosis of the disease. Prenatal diagnosis of GAII has been reported in several cases (8)(9)(10)(11)(12)(13)(14), by either organic acid analysis of the amniotic fluid, or by in vitro oxidation of radioactive substrates by amniocytes. We describe here the prenatal diagnosis of a patient with a mild form of GAII caused by an ETF deficiency accomplished by immunochemical procedures and, retrospectively, by organic acid analysis of amniotic fluid, using a stable isotope dilution method (2).…”

Stable isotope dilution analysis ofN‐acetylaspartic acid in CSF, blood, urine and amniotic fluid: Accurate postnatal diagnosis and the potential for prenatal diagnosis of canavan disease

“…For several organic acidurias quantitation of specific metabolites in amniotic fluid is a reliable and fast method for prenatal diagnosis (Sweetman, 1984;Jakobs et al 1990). We therefore developed a sensitive and accurate stable isotope dilution method for the quantitation of NAA in amniotic fluid.…”