Abstract：
OBJECTIVE: To systematically review the literature for reports on Wolcott-Rallison syndrome, focusing on the spectrum and natural history, genotype-phenotype correlations, patient and native liver survival, and long-term outcomes.
METHODS: PubMed, Livio, Google Scholar, Scopus and Web of Science databases were searched. Data on genotype, phenotype, therapy, cause of death and follow-up were extracted. Survival and correlation analyses were performed.
RESULTS: Sixty-two studies with 159 patients met the inclusion criteria and additional 30 WRS individuals were collected by personal contact. The median age of presentation was 2.5 months (IQR 2) and of death was 36 months (IQR 50.75). The most frequent clinical feature was neonatal diabetes in all patients, followed by liver impairment in 73%, impaired growth in 72%, skeletal abnormalities in 59.8%, the nervous system in 37.6%, the kidney in 35.4%, insufficient haematopoiesis in 34.4%, hypothyroidism in 14.8% and exocrine pancreas insufficiency in 10.6%. Episodes of acute liver failure were frequently reported. Liver transplantation was performed in six, combined liver-pancreas in one and combined liver-pancreas-kidney transplantation in two individuals. Patient survival was significantly better in the transplant cohort (p = .0057). One-, five- and ten-year patient survival rates were 89.4%, 65.5% and 53.1%, respectively. Liver failure was reported as the leading cause of death in 17.9% of cases. Overall survival was better in individuals with missense mutations (p = .013).
CONCLUSIONS: Wolcott-Rallison syndrome has variable clinical courses. Overall survival is better in individuals with missense mutations. Liver- or multi-organ transplantation is a feasible treatment option to improve survival.
METHODS: PubMed, Livio, Google Scholar, Scopus and Web of Science databases were searched. Data on genotype, phenotype, therapy, cause of death and follow-up were extracted. Survival and correlation analyses were performed.
RESULTS: Sixty-two studies with 159 patients met the inclusion criteria and additional 30 WRS individuals were collected by personal contact. The median age of presentation was 2.5 months (IQR 2) and of death was 36 months (IQR 50.75). The most frequent clinical feature was neonatal diabetes in all patients, followed by liver impairment in 73%, impaired growth in 72%, skeletal abnormalities in 59.8%, the nervous system in 37.6%, the kidney in 35.4%, insufficient haematopoiesis in 34.4%, hypothyroidism in 14.8% and exocrine pancreas insufficiency in 10.6%. Episodes of acute liver failure were frequently reported. Liver transplantation was performed in six, combined liver-pancreas in one and combined liver-pancreas-kidney transplantation in two individuals. Patient survival was significantly better in the transplant cohort (p = .0057). One-, five- and ten-year patient survival rates were 89.4%, 65.5% and 53.1%, respectively. Liver failure was reported as the leading cause of death in 17.9% of cases. Overall survival was better in individuals with missense mutations (p = .013).
CONCLUSIONS: Wolcott-Rallison syndrome has variable clinical courses. Overall survival is better in individuals with missense mutations. Liver- or multi-organ transplantation is a feasible treatment option to improve survival.
摘要：
目的：系统回顾有关Wolcott-Rallison综合征的文献，专注于光谱和自然历史，基因型-表型相关性，患者和天然肝脏存活率，和长期结果。
方法：PubMed，Livio,谷歌学者，搜索了Scopus和WebofScience数据库。基因型数据，表型,治疗,提取死亡原因和随访。进行生存和相关性分析。
结果：62项研究中有159名患者符合纳入标准，另外30名WRS个体通过个人接触收集。中位就诊年龄为2.5个月（IQR2），死亡年龄为36个月（IQR50.75）。最常见的临床特征是所有患者的新生儿糖尿病，其次是73%的肝功能损害，72%的增长受损，骨骼异常占59.8%，在37.6%的神经系统，肾脏占35.4%，34.4%的人造血不足，甲状腺功能减退症占14.8%，胰腺外分泌功能不全占10.6%。经常报告急性肝功能衰竭的发作。6例进行肝移植,1例联合肝胰脏和2例联合肝胰肾移植。移植队列中的患者存活率显著更好(p=.0057)。一个-，患者五年和十年生存率为89.4%，65.5%和53.1%，分别。据报道，在17.9％的病例中，肝功能衰竭是导致死亡的主要原因。具有错义突变的个体的总体生存率更好(p=.013)。
结论：Wolcott-Rallison综合征具有不同的临床病程。具有错义突变的个体的总体生存率更好。肝脏或多器官移植是提高生存率的可行治疗选择。
方法：PubMed，Livio,谷歌学者，搜索了Scopus和WebofScience数据库。基因型数据，表型,治疗,提取死亡原因和随访。进行生存和相关性分析。
结果：62项研究中有159名患者符合纳入标准，另外30名WRS个体通过个人接触收集。中位就诊年龄为2.5个月（IQR2），死亡年龄为36个月（IQR50.75）。最常见的临床特征是所有患者的新生儿糖尿病，其次是73%的肝功能损害，72%的增长受损，骨骼异常占59.8%，在37.6%的神经系统，肾脏占35.4%，34.4%的人造血不足，甲状腺功能减退症占14.8%，胰腺外分泌功能不全占10.6%。经常报告急性肝功能衰竭的发作。6例进行肝移植,1例联合肝胰脏和2例联合肝胰肾移植。移植队列中的患者存活率显著更好(p=.0057)。一个-，患者五年和十年生存率为89.4%，65.5%和53.1%，分别。据报道，在17.9％的病例中，肝功能衰竭是导致死亡的主要原因。具有错义突变的个体的总体生存率更好(p=.013)。
结论：Wolcott-Rallison综合征具有不同的临床病程。具有错义突变的个体的总体生存率更好。肝脏或多器官移植是提高生存率的可行治疗选择。
