Are asymptomatic carriers of OTC deficiency always asymptomatic? A multicentric retrospective study of risk using the UCDC longitudinal study database

作者：Kuntal Sen, Rima Izem, Yuelin Long, Jiji Jiang, Laura Konczal, Robert McCarter, Andrea Gropman, Jirair K. Bedoyan · 发表于：Molecular Genetics & Genomic Medicine · 年份：2024 · DOI：10.1002/mgg3.2443 · 被引用次数：14 · 研究领域：Metabolism and Genetic Disorders、Folate and B Vitamins Research、Mitochondrial Function and Pathology

BACKGROUND: Ornithine transcarbamylase deficiency (OTCD) due to an X-linked OTC mutation, is responsible for moderate to severe hyperammonemia (HA) with substantial morbidity and mortality. About 80% of females with OTCD remain apparently "asymptomatic" with limited studies of their clinical characteristics and long-term health vulnerabilities. Multimodal neuroimaging studies and executive function testing have shown that asymptomatic females exhibit limitations when stressed to perform at higher cognitive load and had reduced activation of the prefrontal cortex. This retrospective study aims to improve understanding of factors that might predict development of defined complications and serious illness in apparent asymptomatic females. A proband and her daughter are presented to highlight the utility of multimodal neuroimaging studies and to underscore that asymptomatic females with OTCD are not always asymptomatic. METHODS: We review data from 302 heterozygote females with OTCD enrolled in the Urea Cycle Disorders Consortium (UCDC) longitudinal natural history database. We apply multiple neuroimaging modalities in the workup of a proband and her daughter. RESULTS: Among the females in the database, 143 were noted as symptomatic at baseline (Sym). We focused on females who were asymptomatic (Asx, n = 111) and those who were asymptomatic initially upon enrollment in study but who later became symptomatic sometime during follow-up (Asx/Sym, n = 22). The majority of Asx (86%) an...