ABSTRACT
Abstract X-linked ornithine transcarbamylase deficiency (OTCD) is the most common urea cycle disorder. Hemizygous males with complete deficiency manifest neonatal acute hyperammonemia, while those with partial deficiency have a late presentation. The symptomatology of heterozygotes depends on the inactivation pattern of X chromosome. Hyperammonemic episodes can cause neurological damage and are potentially fatal. Here, we match clinical, biochemical, and molecular findings with bioinformatics analyses to report genotype-phenotype correlations in 14 Argentine patients with OTCD from 11 unrelated families: 4 hemizygotes with neonatal onset (complete OTC gene deletion, 533C > T, c.540+1G > A, c.697delG); 4 hemizygotes with late onset (c.216+1G > A, c.386G > A, c.622G > A, c.829C > T); and 6 symptomatic heterozygotes (complete OTC gene deletion, c.533C > T, c.452T > G, c.540+1G > A, dupE1-9/delE10). Three of these mutations were previously unreported: c.540+1G > A, c.697delG, and dup1-9/del10. Our data highlight the relevance of combining molecular and bioinformatics analyses for accurate diagnosis and outcome prediction in suspected patients with OTCD and the importance of carrier testing for effective genetic counseling.