Ornithine carbamoyltransferase (OCT; EC 2.1.3.3) deficiency, an X-linked disorder (McKusick 31125) presents many forms of onset in male patients (Walser, 1983) with residual hepatic activity for OCT ranging from zero to subnormal values (Briand et al., 1982; Rabier et al., 1989). This report describes a patient with an almost normal OCT activity when determined in optimal conditions. L.H. was the second boy from non-consanguineous parents, the first being clinically normal. At 10 months he was noticed to have slight psychomotor delay and slight hypotonia. When 13 months old he was hospitalized for convulsions. At this time the plasma ammonia was 180 #mol/L (controls < 50 #mol/L). The chromatography of plasma amino acids showed normal concentrations of glutamate + glutamine (558 #tool/L; controls (mean _+ SD) 578 _+ 92#tool/L) and of lysine (183 #tool/L; controls 183 ___ 39#tool/L) and decreased concentrations of citrulline (10#tool/L; controls 26 _+ 7 #mol/L), ornithine (39 #tool/L; controls 72 _+ 25 #mol/L) and arginine (58#mol/L; controls 77 _+ 20#mol/L). Urinary organic acids, investigated by gas chromatography-mass spectrometry, showed abnormal levels of uracil and pyroglutamic acid. Urinary orotic acid was only slightly increased at 9.5#mol/(mmol creatinine) (controls < 6 #mol/(mmol creatinine)). Dysfunction of the mitochondrial part of the urea cycle was suspected, but enzymatic investigation was not performed at this time. At 18 months he was admitted in another hospital for convulsions and seizures associated with fever. Brain CT scan was normal. Five months later he was readmitted for seizures, respiratory distress and myoclonia. Brain CT scan showed cortical atrophy. Plasma ammonia was 300 #mol/L and lactate 8.4 mmot/L. Liver dysfunction was noticed (elevated transaminases and decreased blood coagulation factors). Brain dysfunction appeared progressively until he died 3 days after his admission in the intensive care unit. Before death, plasma ammonia decreased spontaneously to 30#mol/L and urinary orotic acid was 133#mol/(mmol creatinine) suggesting an OCT deficiency. Investigation of OCT in a post-mortem liver specimen showed a quite elevated enzyme residual activity (17.9 _+ 8.9 #tool h1 (mg protein)1; range 8.9-29.5 ; controls 35.5 +9 .6#molh -1 (mg protein) -1) when optimal concentrations of ornithine (t.8 mmol/L) and of carbamoylphosphate (5 mmol/L) were used. Abnormal Km for L-ornithine was observed (Kin patient 2.0 mmol/L; Km controls 0.33 +_ 0.01 mmol/L). The K m for carbamoylphosphate was normal.