Department of Pediatric Endocrinology and Genetic Metabolism, Shanghai Institute for Pediatric Research, Xinhua Hospital Affiliated To Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Neurology, Shanghai Children's Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine, National Children's Medical Center, Shanghai, China.
Orphanet J Rare Dis. 2020 Dec 3;15(1):340. doi: 10.1186/s13023-020-01606-2.
This study aimed to describe the clinical and biochemical features of Chinese patients with ornithine transcarbamylase deficiency (OTCD), and to investigate the mutation spectrum of OTC gene and their potential correlation with phenotype.
Sixty-nine patients with OTCD were enrolled between 2004 and 2019. Clinical and laboratory data were reviewed retrospectively from medical records.
Fifteen cases (13 males, 2 females) presented with early onset; 53 cases (21 males, 32 females) had late onset, and one female was asymptomatic. The median onset age was 1.5 years (range 1 day-56 years). Urine orotic acid levels were increased in all patients tested, while only 47.6% of patients showed decreased serum levels of citrulline. The peak plasma ammonia levels were higher in early-onset patients than in late-onset patients (P < 0.01). Fifty-four different mutations of OTC gene were identified and 18 of them were novel. R277W (10.6%) was the most common mutation, followed by G195R (4.6%) and A209V (3.0%). By June 2019, 41 patients had survived, 24 were deceased, and 4 were lost to follow-up. Among the survivors, 13 patients had received liver transplantation at a median age of 3 years, with a one-year survival rate of 100%. The mortality of OTCD is extremely high among patients with early onset (80.0% versus 24.5% in patients with late onset).
The evaluation of serum citrulline level is of limited value in diagnosis of OTCD, while urine orotic acid detection and genetic testing are more helpful.
本研究旨在描述中国鸟氨酸氨甲酰基转移酶缺乏症（OTCD）患者的临床和生化特征，并探讨 OTC 基因突变谱及其与表型的潜在相关性。
2004 年至 2019 年间共纳入 69 例 OTCD 患者。回顾性分析病历中的临床和实验室数据。
15 例（13 例男性，2 例女性）表现为早发型；53 例（21 例男性，32 例女性）为晚发型，1 例女性无症状。中位发病年龄为 1.5 岁（范围 1 天-56 岁）。所有检测患者的尿液乳清酸水平均升高，而仅 47.6%的患者血清瓜氨酸水平降低。早发型患者的血浆氨峰值高于晚发型患者（P<0.01）。共鉴定出 54 种 OTC 基因突变，其中 18 种为新突变。R277W（10.6%）是最常见的突变，其次是 G195R（4.6%）和 A209V（3.0%）。截至 2019 年 6 月，41 例患者存活，24 例死亡，4 例失访。在存活者中，13 例患者在中位年龄 3 岁时接受了肝移植，1 年生存率为 100%。早发型患者的死亡率极高（80.0%比晚发型患者的 24.5%）。
血清瓜氨酸水平的评估对 OTCD 的诊断价值有限，而尿液乳清酸检测和基因检测更有帮助。
