背景:本研究旨在调查中国东南部10例鸟氨酸氨基甲酰转移酶缺乏症(OTCD)儿童的临床和分子遗传学特征,以及OTCD基因型和表型之间的相关性。
方法:对其临床表现进行回顾性分析,实验室测试,2015年8月至2021年10月在中国福建省泉州市妇幼保健院收治的10例OTCD患儿的基因检测结果。
结果:五个男孩出现早发性症状,包括食欲不振,困倦,呻吟,癫痫发作,和肝功能衰竭。相比之下,5例患者(1男4女)以晚发性胃肠道症状为主要临床表现,都表现为肝功能损害,和四个肝衰竭。鉴定了9种不同的OTC基因变体,包括两个新的突变:c.1033del(p。Y345Tfs*50)和c.167T>A(p。M56K)。在七个死亡的病人中,尽管积极治疗,5人仍有早发性疾病.三名患者幸存下来,其中两人接受了肝移植。
结论:OTCD的临床表现缺乏特异性。然而,血氨水平升高是OTCD的重要诊断线索.基因检测有助于临床医生更准确的诊断和预后评估。此外,我们确定了两个新的致病变异,并扩大了OTC基因的突变谱,这可能有助于更好地了解OTCD患者的临床和遗传特征。
BACKGROUND: This 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.
METHODS: A retrospective analysis was performed on the clinical manifestations, laboratory testing, and genetic test findings of ten children with OTCD admitted between August 2015 and October 2021 at Quanzhou Maternity and Children\'s Hospital of Fujian Province in
China.
RESULTS: Five boys presented with early-onset symptoms, including poor appetite, drowsiness, groaning, seizures, and liver failure. In contrast, five patients (one boy and four girls) had late-onset gastrointestinal symptoms as the primary clinical manifestation, all presenting with hepatic impairment, and four with hepatic failure.Nine distinct variants of the OTC gene were identified, including two novel mutations: c.1033del(p.Y345Tfs*50) and c.167T > A(p.M56K). Of seven patients who died, five had early-onset disease despite active treatment. Three patients survived, and two of them underwent liver transplantation.
CONCLUSIONS: The clinical manifestations of OTCD lack specificity. However, elevated blood ammonia levels serve as a crucial diagnostic clue for OTCD. Genetic testing aids in more accurate diagnosis and prognosis assessment by clinicians. In addition, we identified two novel pathogenic variants and expand the mutational spectrum of the gene OTC, which may contribute to a better understanding of the clinical and genetic characteristics of OTCD patients.