Long-term outcomes in Ornithine Transcarbamylase deficiency: a series of 90 patients.
Long-term outcomes in Ornithine Transcarbamylase deficiency: a series of 90 patients.
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DOI：
10.1186/s13023-015-0266-1
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发表时间：
2015-05-10
影响因子：
3.7
通讯作者：
De Lonlay P
中科院分区：
文献类型：
--
作者：
Brassier A;Gobin S;Arnoux JB;Valayannopoulos V;Habarou F;Kossorotoff M;Servais A;Barbier V;Dubois S;Touati G;Barouki R;Lesage F;Dupic L;Bonnefont JP;Ottolenghi C;De Lonlay P
本研究的主要目的是调查在一家医疗中心随访的大型鸟氨酸转氨甲酰酶缺乏症（OTCD）患者队列的长期结局。我们分析了1971年至2011年间90例OTCD患者（84个家族，48例男性和42例女性）的临床、生化和遗传参数。27名患者（22名男孩，5名女孩）有新生儿表现; 52名患者有“中间”迟发性形式的疾病（21名男孩，31名女孩），在1个月至16岁之间发现; 11名患者（5名男孩，6名女孩）在成年期（16至55岁）。有新生儿表现的患者在诊断时死亡率增加（90% vs 13%，晚发型），血浆氨峰值（平均值：960 μmol/L vs 500 μmol/L）和谷氨酰胺峰值（平均值：4110 μmol/L vs 1000 μmol/L）水平升高。所有的新生儿形式都显示出更多的急性失代偿（平均值：6.2/例，婴儿和成人分别为2.5和1.4）。在成人组中，一些患者最近甚至在第一次昏迷时死亡。分子分析在研究的68名患者中的59名中鉴定出有害突变。单碱基替换比缺失更常见（分别为69%和12%），在晚发型组中发现了复发性突变（pArg 40 His;婴儿为13%，成人为57%）;遗传性突变占病例的一半。新生儿组和晚发型组存活患者的神经功能评分无显著差异，且与诊断时的氨峰值和血浆谷氨酰胺浓度无关。然而，在晚发型疾病中，根据诊断时谷氨酰胺/瓜氨酸比值调整的氨水平是低智商的临界预测因子（logistic回归分析p = 0.12;受试者工作特征曲线下面积为76%，p <0.05）。OTCD仍然是一种严重的疾病，即使在成人发病的患者中，预防代谢失代偿也是至关重要的。生化标志物的组合保证了进一步的研究，以提供关于OTCD患者神经学结局的额外预后信息。
The principal aim of this study was to investigate the long-term outcomes of a large cohort of patients with ornithine transcarbamylase deficiency (OTCD) who were followed up at a single medical center. We analyzed clinical, biochemical and genetic parameters of 90 patients (84 families, 48 males and 42 females) with OTCD between 1971 and 2011. Twenty-seven patients (22 boys, 5 girls) had a neonatal presentation; 52 patients had an “intermediate” late-onset form of the disease (21 boys, 31 girls) that was revealed between 1 month and 16 years; and 11 patients (5 boys, 6 girls) presented in adulthood (16 to 55 years). Patients with a neonatal presentation had increased mortality (90% versus 13% in late-onset forms) and peak plasma ammonium (mean value: 960 μmol/L versus 500 μmol/L) and glutamine (mean value: 4110 μmol/L versus 1000 μmol/L) levels at diagnosis. All of the neonatal forms displayed a greater number of acute decompensations (mean value: 6.2/patient versus 2.5 and 1.4 in infants and adults, respectively). In the adult group, some patients even recently died at the time of presentation during their first episode of coma. Molecular analyses identified a deleterious mutation in 59/68 patients investigated. Single base substitutions were detected more frequently than deletions (69% and 12%, respectively), with a recurrent mutation identified in the late-onset groups (pArg40 His; 13% in infants, 57% in adults); inherited mutations represented half of the cases. The neurological score did not differ significantly between the patients who were alive in the neonatal or late-onset groups and did not correlate with the peak ammonia and plasma glutamine concentrations at diagnosis. However, in late-onset forms of the disease, ammonia levels adjusted according to the glutamine/citrulline ratio at diagnosis were borderline predictors of low IQ (p = 0.12 by logistic regression; area under the receiver operating characteristic curve of 76%, p <0.05). OTCD remains a severe disease, even in adult-onset patients for whom the prevention of metabolic decompensations is crucial. The combination of biochemical markers warrants further investigations to provide additional prognostic information regarding the neurological outcomes of patients with OTCD.
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影响因子：
4
作者：
Matsuda, I;Matsuura, T;Yoshino, M
通讯作者：
Yoshino, M
影响因子：
3.6
作者：
TUCHMAN, M;TSAI, MY;BRUSILOW, SW
通讯作者：
BRUSILOW, SW
影响因子：
4.2
作者：
Kido, Jun;Nakamura, Kimitoshi;Endo, Fumio
通讯作者：
Endo, Fumio
影响因子：
3.7
作者：
Häberle J;Boddaert N;Burlina A;Chakrapani A;Dixon M;Huemer M;Karall D;Martinelli D;Crespo PS;Santer R;Servais A;Valayannopoulos V;Lindner M;Rubio V;Dionisi-Vici C
通讯作者：
Dionisi-Vici C
影响因子：
3.7
作者：
Cavicchi C;Donati M;Parini R;Rigoldi M;Bernardi M;Orfei F;Gentiloni Silveri N;Colasante A;Funghini S;Catarzi S;Pasquini E;la Marca G;Mooney S;Guerrini R;Morrone A
通讯作者：
Morrone A