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.


METHODS
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.


CONCLUSIONS
Fetal mitochondrial trifunctional protein defects should be considered a cause for maternal liver disease, preterm labor, and intrauterine growth retardation.
Yang
Zi
Z
Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Zhao
Yiwen
Y
Bennett
Michael J
MJ
Strauss
Arnold W
AW
Ibdah
Jamal A
JA
D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000172:deficiency / Q000235:genetics; D001724:Birth Weight; D005260:Female; D005317:Fetal Growth Retardation / Q000209:etiology; D005838:Genotype; D006801:Humans; D063989:Long-Chain-3-Hydroxyacyl-CoA Dehydrogenase; D063991:Mitochondrial Trifunctional Protein; D009097:Multienzyme Complexes / Q000235:genetics*; D009154:Mutation; D007752:Obstetric Labor, Premature / Q000209:etiology; D011247:Pregnancy; D011256:Pregnancy Outcome
D009097:Multienzyme Complexes; D015094:3-Hydroxyacyl CoA Dehydrogenases; D063989:Long-Chain-3-Hydroxyacyl-CoA Dehydrogenase; D063991:Mitochondrial Trifunctional Protein