Molecular prenatal diagnosis in families with fetal mitochondrial trifunctional protein mutations

Objectives: To evaluate the feasibility of molecular prenatal diagnosis in families with mitochondrial trifunctional protein (TFP) mutations and prosp ectively study the effects of fetal genotype on pregnancy outcome. TFP cata lyzes the last 3 steps in mitochondrial long-chain fatty acid oxidation. Study design: We performed molecular prenatal diagnosis in 9 pregnancies, 8 in 6 families with isolated long-chain 3-hydroxyacyl-coenzyme A dehydrogen ase (LCHAD) deficiency and one in a family with complete TFP deficiency. An alyses were performed on chorionic villous samples in 7 pregnancies and on amniocytes in 2. Results: Molecular prenatal diagnosis successfully identified the fetal gen otype in all 9 pregnancies. Two fetuses were affected, and both pregnancies were terminated by family decision. Two other fetuses had normal genotype and 5 others were heterozygotes. These 7 pregnancies were uncomplicated, an d all the offspring are alive and apparently healthy. Genotypes of the abor ted fetuses and neonates were confirmed by molecular analysis and enzymatic assays. Conclusions: Molecular prenatal diagnosis is possible and valid in guiding management of pregnancies in families with known TFP defects. Women heteroz ygous for TFP alpha -subunit mutations who carry fetuses with wildtype or h eterozygous genotypes have uncomplicated pregnancies.