Ultrastructural pathology in congenital defects of the urea cycle: Ornithine transcarbamylase and carbamylphosphate synthetase deficiency

Summary Inborn defects of urea synthesis, leading to hyperammonemia, are complex inherited disorders, whose structural sequelae in different tissues and organs have not yet been studied in detail. Ultrastructural investigations have been performed on two cases of deficiencies of two consecutive enzymes of the urea cycle, carbamylphosphate synthetase and ornithine transcarbamylase, and the findings are compared with previously reported results. With regard to liver pathology it appeared that 1). Hepatocytes in CPS deficiency mainly exhibited changes of SER and mitochondrial compartments, whereas 2). OTC deficiency was characterized by regressive liver cell change, with abnormal configuration of the RER, formation of telolysosomes and peribiliary vesiculation. It is suggested that the mitochondrial disorder in the CPS defect is directly related to the lack of a major enzyme protein in this organelle, resulting in structural damage. The leading renal change in CPS deficiency is foot process fusion of glomerular podocytes. Brain alteration in this disorder is similar to that reported for other hyperammonaemic urea cycle defects.