LRPPRC mutations cause a phenotypically distinct form of Leigh syndrome with cytochrome c oxidase deficiency
LRPPRC mutations cause a phenotypically distinct form of Leigh syndrome with cytochrome c oxidase deficiency
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DOI：
10.1136/jmg.2010.081976
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发表时间：
2011-03-01
影响因子：
4
通讯作者：
Mitchell, Grant A.
中科院分区：
文献类型：
--
作者：
Debray, Francois-Guillaume;Morin, Charles;Mitchell, Grant A.
背景的自然历史的所有已知的患者与法裔加拿大Leigh病（Saguenay-Lac-St-Jean细胞色素c氧化酶缺乏症，MIM220111，SLSJ-COX），最大的已知队列的患者具有遗传同质性，核编码的先天性乳酸酸中毒，进行了研究。一个是遗传复合物（A354V/C1277Xdel8）。临床特征包括发育迟缓、发育不全、特征性面部外观，以及90%的患者出现之前未详细描述的代谢性（暴发性乳酸酸中毒）和/或神经性（Leigh综合征和/或卒中样发作）急性危象。生存期从5天到> 30年不等。46/56例患者（82%）死亡，中位年龄为1.6岁。在73例危象中，38例（52%）是致命的。死亡的直接原因是多器官衰竭和/或Leigh病。危机期间死亡率的主要预测因素（p
Background The natural history of all known patients with French-Canadian Leigh disease (Saguenay-Lac-St-Jean cytochrome c oxidase deficiency, MIM220111, SLSJ-COX), the largest known cohort of patients with a genetically homogeneous, nuclear encoded congenital lactic acidosis, was studied.Results 55 of 56 patients were homozygous for the A354V mutation in LRPPRC. One was a genetic compound (A354V/C1277Xdel8). Clinical features included developmental delay, failure to thrive, characteristic facial appearance and, in 90% of patients, acute crises that have not previously been detailed, either metabolic (fulminant lactic acidosis) and/or neurological (Leigh syndrome and/or stroke-like episodes). Survival ranged from 5 days to >30 years. 46/56 patients (82%) died, at a median age of 1.6 years. Of 73 crises, 38 (52%) were fatal. The immediate causes of death were multiple organ failure and/or Leigh disease. Major predictors of mortality during crises (p