A longitudinal study of urea cycle disorders.
A longitudinal study of urea cycle disorders.
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DOI：
10.1016/j.ymgme.2014.08.001
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发表时间：
2014-09
影响因子：
3.8
通讯作者：
Seminara, Jennifer
中科院分区：
文献类型：
--
作者：
Batshaw, Mark L.;Tuchman, Mendel;Summar, Marshall;Seminara, Jennifer
关键词：
尿素循环障碍联盟（UCDC）是美国国立卫生研究院资助的罕见疾病临床研究网络的成员，正在对8种尿素循环障碍（UCD）进行纵向研究，最初招募于2006年开始。该联盟由美国的14个地点组成，加拿大和欧洲。本报告总结了614例UCD患者的数据挖掘研究，这些患者参加了UCDC的纵向研究方案。最常见的疾病是鸟氨酸转氨甲酰酶缺乏症，占参与者的一半以上。我们计算出尿素循环障碍的总患病率为1/35，000，其中2/3的患者在新生儿期后出现初始症状。我们发现新生儿发病病例的死亡率为24%，晚发病例为11%。新生儿后期临床高氨血症发作最常见的促发因素是并发感染。血氨和谷氨酰胺的升高似乎是神经认知结果的生物标志物。在长期治疗方面，低蛋白饮食似乎导致正常体重，但线性生长下降，而苯丁酸盐的N-清除剂治疗导致支链氨基酸水平低。最后，我们发现鸟氨酸转氨甲酰酶缺乏症患者发生肝功能障碍的风险出乎意料的高。这项自然史研究说明了一种罕见遗传性疾病的合作研究如何能够提高对发病率和疾病结局的理解。
The urea cycle disorders consortium (UCDC) is a member of the NIH funded Rare Diseases Clinical Research Network and is performing a longitudinal study of 8 urea cycle disorders (UCD) with initial enrollment beginning in 2006. The consortium consists of 14 sites in the U.S., Canada and Europe. This report summarizes data mining studies of 614 patients with UCD enrolled in the UCDC’s longitudinal study protocol. The most common disorder is ornithine transcarbamylase deficiency, accounting for more than half of the participants. We calculated the overall prevalence of urea cycle disorders to be 1/35,000, with 2/3rds presenting initial symptoms after the newborn period. We found the mortality rate to be 24% in neonatal onset cases and 11% in late onset cases. The most common precipitant of clinical hyperammonemic episodes in the post-neonatal period was intercurrent infections. Elevations in both blood ammonia and glutamine appeared to be biomarkers for neurocognitive outcome. In terms of chronic treatment, low protein diet appeared to result in normal weight but decreased linear growth while N-scavenger therapy with phenybutyrate resulted in low levels of branched chain amino acids. Finally, we found an unexpectedly high risk for hepatic dysfunction in patients with ornithine transcarbamylase deficiency. This natural history study illustrates how a collaborative study of a rare genetic disorder can result in an improved understanding of morbidity and disease outcome.
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影响因子：
5.1
作者：
Batshaw, ML;MacArthur, RB;Tuchman, M
通讯作者：
Tuchman, M
影响因子：
158.5
作者：
BATSHAW, ML;BRUSILOW, S;SCHAFER, IA
通讯作者：
SCHAFER, IA
影响因子：
5.1
作者：
Summar, M;Tuchman, M
通讯作者：
Tuchman, M
影响因子：
158.5
作者：
MSALL, M;BATSHAW, ML;MELLITS, ED
通讯作者：
MELLITS, ED
影响因子：
8.3
作者：
Summar, ML;Gainer, JV;Brown, NJ
通讯作者：
Brown, NJ