Pediat. R e s . 9: 488--497 (1975) Extract Six related subjects with severe feeding problems in infancy, hyperammonemia, hyperornithinenia, and homocitrullinuria are reported. The clinical picture includes episodic motor and mental impairment, seizures, intellectual deficits that vary from severe to very mild and, in two cases, a bleeding tendency early in life. The pedigree indicates autosomal recessive inheritance.C a r b a m y l p h o s p h a t e synthetase I hyperornithinemia hoinocitrulliriuria leukocytes h y p e r a m m o n e m i aIn a liver biopsy in one patient decreased activity of carbamyl phosphate synthetase I ( C P S I, EC. 2.7.2.5) was found. Enzymatic assays on peripheral leukocytes in all six subjects confirmed the liver results. Loading studies with ornithine and citrulline were consistent with a defect early in the urea cycle. Homocitrullinuria appeared to arise from excessive synthesis from lysine, but there was no impairment of the main lysine catabolic pathway.Large and bizarrely shaped hepatic mitochondria with curious periodic (35@400W) membranes were observed ultrastructurally. SpeculationClinical entities in which liver C P S I deficiency has been reported represent a heterogeneous group. This heterogeneity may arise because the assays currently in use do not differentiate between individual steps in the complex synthetic reaction catalyzed by this enzyme. Associated abnormalities in ornithine transport into the hepatic mitochondria in some may also contribute to the varying expression of this group of disorders. It is conceivable that some unusual periodic structures observed just inside the inner mitochondrial membranes are related to altered ornithine mitochondria1 entry.This disorder adds to the evidence from other inborn errors that there are one or more ways in which lysine metabolism and the urea cycle are specifically interrelated, but the details remain obscure.In 1969 Shih et al. (23) described a patient with hyperammonemia who could be differentiated from the growing group of specific inherited hyperammonemias by the presence of markedly elevated blood ornithine and urinary homocitrulline in addition to the high levels of blood ammonia. Wright and Pollitt (28) reported briefly a second patient with these features.During the past several years we have had the opportunity to study six related subjects with this disorder, and carry out assays of the urea cycle enzymes on peripheral leukocytes of all, and on liver biopsy in one of these. In addition, ultrastructural examination was carried out on the biopsied hepatic tissue.It is the purpose of this communication to report on the results of the above study with special reference to clinical manifestations, localization of the metabolic block, possible mechanism of produc-48 tion of homocitrullinuria, and correlation of the biochemical and morphologic data. CLINICAL SUMMARIES CASE IThis severely mentally retarded boy, Figure 1 IV-8, first came to our attention at the age of 7 years when increased excretion of ornithine and lysi...

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