Clinical characteristics and molecular genetic analysis of ten cases of ornithine carbamoyltransferase deficiency in southeastern China

Abstract

BackgroundThis study aimed to investigate the clinical and molecular genetic characteristics of ten children with ornithine carbamoyltransferase deficiency (OTCD) in southeastern China, as well as the correlation between the genotype and phenotype of OTCD. MethodsThe clinical manifestations, laboratory testing, and genetic test findings of ten children with OTCD admitted between August 2015 and October 2021 were analyzed retrospectively. ResultsFive boys presented with early-onset symptoms, including poor appetite, drowsiness, groaning, seizures, and liver failure. Five patients (one boy and four girls) had late-onset gastrointestinal symptoms as the primary clinical manifestation, all with hepatic impairment, and four with hepatic failure. Coagulopathy occurred in eight patients. Urinary orotic acid levels were elevated in all patients except in one who received blood purification therapy. Only six patients showed decreased serum citrulline levels. Nine distinct variants of the OTC gene were identified, including two novel mutations: c.1033del(p.Y345Tfs*50) and c.167T>A(p.M56K). Despite active treatment, seven patients died, of whom five had early-onset disease. Three patients survived, and two underwent liver transplantation. ConclusionsThe clinical manifestations of OTCD lack specificity. Elevated blood ammonia is a diagnostic clue for OTCD, elevated urinary orotate is specific for its diagnosis, and genetic testing can help confirm the diagnosis. These two novel variants expand the mutational spectra of OTC, which may contribute to a better understanding of the clinical and genetic characteristics of patients with OTCD.