Clinical outcomes and the mutation spectrum of the OTC gene in patients with ornithine transcarbamylase deficiency

Ornithine transcarbamylase (otc) deficiency is an x-linked inborn error of the urea cycle that leads to the accumulation of ammonia, resulting in neurological deficits. this study was performed to describe the clinical outcomes, biochemical features and molecular spectra of patients with otc deficiency. a total of 49 patients from 47 unrelated korean pedigrees were included who were diagnosed with otc deficiency based on biochemical findings and molecular analyses. patient clinical features, biochemical findings and molecular data were analyzed retrospectively. males with neonatal-onset phenotype presented with seizure or altered mentality (n=20). biochemical findings showed high blood ammonia (1132.5±851.6 μmol l−1) and urine orotic acid (1840.7±1731.3 mmol mol−1 cr) levels. there were also five males with late-onset disease who presented with vomiting, irritability and seizure at age 8.2±9.4 years old (range, 0.6–20 years). symptomatic females presented with vomiting, seizure, and altered mentality at age 3.5±3.5 years (range, 0.2–12.8 years; n=24). more males with the late-onset form and symptomatic females displayed mild hyperammonemia and orotic aciduria compared with those showing a neonatal phenotype (p<0.05). molecular analysis identified 37 different mutations (22 missense, 5 large deletions, 4 small deletions, 1 insertion, 3 nonsense and 2 splice sites) from all 49 patients; the mutations were dispersed throughout all coding exons. in korean patients with otc deficiency, mutations in otc are genetically heterogeneous. male patients with the neonatal-onset phenotype showed poor outcomes because of severe hyperammonemia. early diagnosis and interventions for hyperammonemia can provide more favorable prognosis.