Abnormalities of hepatic mitochondrial urea-cycle enzyme activities and hepatic ultrastructure in acute fatty liver of pregnancy.

Two patients presenting with acute fatty liver of pregnancy were studied. Because of similarities between acute fatty liver of pregnancy and Reye's syndrome, we investigated hepatic ultrastructure, urea-cycle enzyme activities, and plasma amino acids. Initial liver biopsies obtained 12 and 21 days after the onset of illness demonstrated microvesicular fat deposition and mitochondrial ultrastructural changes, including pleomorphism and abundant crystalline inclusions. In both biopsies, activity of the mitochondrial urea-cycle enzyme OTC was markedly below normal limits. Activity of the other mitochondrial urea-cycle enzyme, CPS, was low in one patient. Abnormalities of these enzymes persisted in second biopsies obtained at 9 and 28 weeks, respectively. By 44 weeks all urea-cycle enzyme activities had returned to normal in one patient. However, in the other patient OTC activity was still reduced at 52 weeks, although it had doubled in comparison to previous biopsies. Morphological changes of the mitochondria generally improved in parallel with the urea-cycle enzymes. Plasma amino acids, obtained at the time of the initial biopsies, demonstrated a generalized hypoaminoacidemia with the exception of glutamate. Serial observations in patients with this rare disease indicate that there are similarities with Reye's syndrome, in particular, reduced activity of the mitochondrial urea-cycle enzymes. But there are important differences. (1) Enzymatic and ultrastructural abnormalities of mitochondria persist for a longer period of time than in Reye's syndrome. (2) Mitochondrial ultrastructure is different. (3) Plasma amino acid profiles are different.