Fetal genotypes and pregnancy outcomes in 35 families with mitochondrial trifunctional protein mutations.

OBJECTIVE

The purpose of this study was to evaluate the effects of fetal genotype on maternal and fetal outcomes in families with mitochondrial trifunctional protein mutations in the United States. Trifunctional protein has 3 enzymatic activities that include long-chain 3-hydroxyacyl-CoA dehydrogenase, which catalyzes long-chain fatty acid beta-oxidation.

STUDY DESIGN

We analyzed pregnancy history and offspring genotypes in 35 families with heterogeneous mutations. The fetal genotype was determined in utero in 11 pregnancies and after birth in 50 pregnancies.

RESULTS

Forty-nine percent of the women who carried affected fetuses had acute fatty liver of pregnancy. Another 11% of the women had the syndrome of hemolysis, elevated liver enzymes, and low platelets, or preeclampsia. All women who had the maternal illness carried fetuses with isolated long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency. Sixty-eight percent and 43% of the affected pregnancies also were associated with premature delivery and intrauterine growth retardation, respectively. No maternal or fetal complications were associated with heterozygous or wild-type fetal genotypes.

CONCLUSION

Fetal mitochondrial trifunctional protein defects should be considered a cause for maternal liver disease, preterm labor, and intrauterine growth retardation.