背景:对于尿素循环障碍(UCD),早发性(EO)患者的比例和死亡率,以及生命一年的结果显示出很大的变异性。我们旨在整合现有证据,为新的诊断和治疗策略创建基准。
方法:Medline搜索1978年至2014年12月22日发表的报告是通过手工搜索完成的。对四种UCD进行了随机效应荟萃分析,氨基甲酰磷酸合成酶1(CPS1D)缺乏,男/女鸟氨酸转碳淀粉酶(OTCDm/f),精氨酸琥珀酸合成酶(ASSD)和裂解酶(ASLD)。通过荟萃回归分析了出版年份和地理区域的影响。
结果:24篇出版物报告了发病时间(n=1542例患者),EO的生存率(n=665例)和生命一年时的结局(n=172例)。EO表现的比例(95%置信区间)为:CPS1D=0.75(0.61;0.88);OTCDm=0.52(0.39;0.65);OTCDf=0.07(0.03;0.11);ASSD=0.65(0.57;0.73);ASLD=0.60(0.44;0.77);对于存活的EO患者:CPS1D=0.64(0.48=0.48研究之间差异较大。出版年份没有影响。欧洲的研究表明,生存率低于日本或美国。
结论:UCD,除了OTCDf,有EO疾病表现的高风险,除了ASLD,新生儿死亡。在超过三十年的时间内没有观察到生存率的改善。地理差异还有待解释。科学家应该考虑对EOUCD自然历史的全面描述,临床医生,卫生政策制定者和指导方针制定者。
BACKGROUND: For urea cycle disorders (UCD), proportions and mortality of early onset (EO) patients, as well as outcome at one year of life show large variability. We aimed to integrate available evidence to create benchmarks for new diagnostic and therapeutic strategies.
METHODS: Medline search for reports published between 1978 and Dec 22, 2014 was completed by hand search. Random effects meta-analysis was done for four UCDs, deficiency of carbamylphosphate synthetase 1 (CPS1D), male/female ornithine transcarbamylase (OTCDm/f), argininosuccinate synthetase (ASSD) and lyase (ASLD). Effects of publication year and geographic area were analysed by meta-regression.
RESULTS: Twenty-four publications report onset time (n = 1542 patients), survival of EO (n = 665 patients) and outcome at one year of life (n = 172 patients). Proportions for EO manifestation (95% confidence interval) were: CPS1D = 0.75 (0.61;0.88); OTCDm = 0.52 (0.39;0.65); OTCDf = 0.07 (0.03;0.11); ASSD = 0.65 (0.57;0.73); ASLD = 0.60 (0.44;0.77); for surviving EO patients: CPS1D = 0.64 (0.50;0.79); OTCDm = 0.40 (0.16;0.64); OTCDf = 0.57 (0.29;0.85); ASSD = 0.67 (0.48;0.86); ASLD = 0.81 (0.68;0.94); and for normal outcome at one year for survivors: CPS1D = 0.20 (0.07;0.38); OTCDm = 0.15 (0.00;0.39); OTCDf no data; ASSD = 0.36 (0.13;0.60); ASLD = 0.36 (0.17;0.58). Between study variation was large. Year of publication had no effect. Studies from Europe showed lower survival rates than those from Japan or USA.
CONCLUSIONS: UCDs, except for OTCDf, have high risks of EO disease manifestation and, except for ASLD, of neonatal death. No improvement of survival was observed over more than three decades. Geographic variation remains to be explained. This comprehensive description of the natural history of EO UCDs should be considered by scientists, clinicians, health policy makers and guideline developers.