Clinical and mutation analysis of 24 Chinese patients with ornithine transcarbamylase deficiency

Abstract

The principal aim of this study was to examine the clinical manifestations, biochemical features, and molecular genetic characteristics of Chinese patients with ornithine transcarbamylase deficiency (OTCD) at a single medical center. We retrospectively analyzed 24 patients (17 males and 7 females) diagnosed with OTCD between 2006 and 2015. Five male patients had a neonatal presentation; 12 male patients had late onset disease and 7 female patients presented as symptomatic. Patients with a neonatal presentation had the highest peak plasma ammonia and glutamine levels at diagnosis with a high mortality (80% vs 16% in late onset disease). Most of the male late onset disease cases displayed neurologic damage with a mild elevation in plasma ammonia, and a significant increase in serum glutamine, which was commonly misdiagnosed as intracranial infection. In the symptomatic female group, mortality was abnormally high in China with some patients dying at the time of presentation during the first episode of hyperammonemia. Refractory hyperammonemia, serious hepatic function damage, recurrent infection and lethal mutation are the main reasons for poor clinical outcomes of the symptomatic females. Molecular analyses identified 19 different mutations, including 3 novel mutations (c.103insA, c.591C>A and c.805G>A).

Clinical and molecular characteristics of 69 Chinese patients with ornithine transcarbamylase deficiency

“…The recurrent sequence variants were R277W, G195R and A209V in this study. If combining with the mutations reported by Shao et al [23], the most frequent OTC mutations in Chinese population were R277W (8/90, 8.9%), R129H (4/90, 4.4%), G195R (3/90, 3.3%), A209V(2/90, 2.2%), P225L (2/90, 2.2%), and N61S (2/90, 2.2%). Herein we tried to discuss the genotype-phenotype correlations of these common mutations.…”

Mutation Spectrum and Genotype–Phenotype Correlation in a Cohort of Argentine Patients with Ornithine Transcarbamylase Deficiency: A Single-Center Experience

“…Compared to other population groups, our patients differed in their phenotypic distribution due to a greater number of symptomatic heterozygotes. 7,12,13 Regarding disease progression, all 4 OTCD males with the neonatal form died, while 3 of 4 males with late onset survived. Neonatal forms were not diagnosed in symptomatic females.…”

Gene Mutation Analysis and Prenatal Diagnosis of the Ornithine Transcarbamylase (OTC) Gene in Two Families with Ornithine Transcarbamylase Deficiency

“…Of the 2 mutations, the c.867+1G>C mutation has already been reported as a pathogenic mutation. It has been shown that OTCD pediatric patients harboring this mutation usually have severe disease onset during the neonatal stage [20]. The c.782T>C mutation is a newly discovered mutation.…”