Sudden unexpected fatal encephalopathy in adults with OTC gene mutations-Clues for early diagnosis and timely treatment.
Sudden unexpected fatal encephalopathy in adults with OTC gene mutations-Clues for early diagnosis and timely treatment.
复制标题
DOI：
10.1186/s13023-014-0105-9
复制
发表时间：
2014-07-16
影响因子：
3.7
通讯作者：
Morrone A
中科院分区：
文献类型：
--
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
X连锁鸟氨酸转氨甲酰酶缺乏症（OTCD）在成人中通常未被识别，因为临床表现是非特异性的，通常是偶发性的，不被沉淀物掩盖，实验室检查结果在急性期以外可能是正常的。因此，如果不及时识别和治疗，可能会导致严重的死亡率。本研究的目的是为识别成人中的OTCD提供线索，并分析与OTC基因突变相互作用的环境因素，这些因素可能引发急性临床表现。我们对5名不相关的迟发性OTCD成人患者（1名女性和4名男性）进行了临床、生化和分子研究，这些患者因最初的致命性脑病而到急诊室（艾德）就诊。分子研究包括先证者和家族成员的OTC基因测序以及新检测到的突变的计算机表征。我们发现了两个新的突变，c.119G>T（p.Arg40Leu）和c.314G>A（p.Gly105Glu），以及三个已知的OTC突变。预测两种新突变均引起结构不稳定，与迟发性OTCD相关。我们还确定，在家庭成员中，8杂合子女性和2半合子无症状男性。患者的病史揭示了潜在的环境触发因素，包括类固醇治疗、化疗、饮食改变和体外受精的激素治疗。本报告提高了艾德医务人员在任何年龄和性别的高氨血症相关突发神经和行为障碍的鉴别诊断中考虑OTCD的意识。它还拓宽了关于遗传和环境因素在决定OTCD表型表达中的组合效应的知识。
X-linked Ornithine Transcarbamylase deficiency (OTCD) is often unrecognized in adults, as clinical manifestations are non-specific, often episodic and unmasked by precipitants, and laboratory findings can be normal outside the acute phase. It may thus be associated with significant mortality if not promptly recognized and treated. The aim of this study was to provide clues for recognition of OTCD in adults and analyze the environmental factors that, interacting with OTC gene mutations, might have triggered acute clinical manifestations. We carried out a clinical, biochemical and molecular study on five unrelated adult patients (one female and four males) with late onset OTCD, who presented to the Emergency Department (ED) with initial fatal encephalopathy. The molecular study consisted of OTC gene sequencing in the probands and family members and in silico characterization of the newly detected mutations. We identified two new, c.119G>T (p.Arg40Leu) and c.314G>A (p.Gly105Glu), and three known OTC mutations. Both new mutations were predicted to cause a structural destabilization, correlating with late onset OTCD. We also identified, among the family members, 8 heterozygous females and 2 hemizygous asymptomatic males. Patients' histories revealed potential environmental triggering factors, including steroid treatment, chemotherapy, diet changes and hormone therapy for in vitro fertilization. This report raises awareness of the ED medical staff in considering OTCD in the differential diagnosis of sudden neurological and behavioural disorders associated with hyperammonemia at any age and in both genders. It also widens the knowledge about combined effect of genetic and environmental factors in determining the phenotypic expression of OTCD.
登录
查看更多内容
影响因子：
3.8
作者：
Bisanzi, S;Morrone, A;Zammarchi, E
通讯作者：
Zammarchi, E
影响因子：
1.1
作者：
Chan, Joseph S.;Harding, Cary O.;Blanke, Charles D.
通讯作者：
Blanke, Charles D.
影响因子：
3.8
作者：
Lichter-Konecki, Uta;Nadkarni, Vinay;Baumgart, Stephen
通讯作者：
Baumgart, Stephen
DOI：
10.1002/prot.340230412
发表时间：
1995-12-01
期刊：
PROTEINS-STRUCTURE FUNCTION AND GENETICS
影响因子：
--
作者：
Frishman, D;Argos, P
通讯作者：
Argos, P
DOI：
10.1016/j.jpba.2009.03.001
发表时间：
2009-07-12
影响因子：
3.4
作者：
Cavicchi, C.;Malvagia, S.;Pasquini, E.
通讯作者：
Pasquini, E.