The liver ultrastructural findings in two girls with partial carbamyl phosphate synthetase I (CPS) deficiency and their heterozygote parents and two siblings with ornithine transcarbamylase (OTC) deficiency are described. Liver ultrastructure in the four patients with inherited deficiences of urea cycle enzymes showed minimal alterations with essentially normal mitochondria when biopsy was performed during periods of good control of their hyperammonemia. Mitochondrial ultrastructure was also essentially normal in the heterozygotes for carbamyl phosphate synthetase I deficiency. These findings are in contrast to the marked alterations in mitochondrial ultrastructure found in the study of two cases of Reye's syndrome in which severe depression of ornithine transcarbamylase and carbamyl phosphate synthetase I activities was noted.
The five enzymes of the urea cycle detoxify ammonia and are primarily located in the liver (refer to Figure 1). Two of these enzymes, ornithine transcarbamylase (OTC) and carbamyl phosphate synthetase I (CPS) are located in the mitochondrial matrix. Inherited partial and complete enzyme deficiencies have been described for both enzymes.
There are 13 reported cases of CPS deficiency in the literature including our own previous reports (1,Z). Light microscopy of the liver, when noted, is described as essentially normal. Only one study comments on ultrastructural features of the affected liver (Hug, G. et al., Pediatr. Res. 1978; 12:437, Abstract).
OTC deficiency is the most frequent inherited abnormality of the urea cycle. Liver histologic changes noted on light microscopy in OTC deficiency include mild steatosis, focal hepatocellular necrosis, inflammation, and well-defined clusters of "pale hepatocytes", especially in heterozygotes (2). Only one abstract (see Hug, G. above) and one case report (3) comment on the liver ultrastructure.
Since CPS and OTC are both localized to the mito-