Acute fatal presentation of ornithine transcarbamylase deficiency in a previously healthy male.
Acute fatal presentation of ornithine transcarbamylase deficiency in a previously healthy male.
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DOI：
10.1007/s12072-008-9078-x
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发表时间：
2008-09
影响因子：
6.6
通讯作者：
Packman, Seymour
中科院分区：
文献类型：
--
作者：
Klein, Ophir D.;Kostiner, Dana R.;Weisiger, Kara;Moffatt, Ellen;Lindeman, Neal;Goodman, Stephen;Tuchman, Mendel;Packman, Seymour
鸟氨酸转氨基甲酰基酶（OTC）缺乏症是一种x连锁尿素循环缺陷。虽然半合子男性通常在婴儿期出现高氨血症昏迷，但也有罕见的迟发性昏迷的报道，在58岁以下的男性中预后较差。与受影响患者具有相同突变的亲属通常没有症状，环境和遗传因素可能影响疾病的外显率和表达。在这里，我们提出了我们的调查患者迟发性表现，我们强调环境和遗传因素对疾病表达的潜在作用。患者为一名健康的62岁男性，在8天的时间内出现智力迟钝、难治性癫痫发作和昏迷。有趣的是，病人最近使用了家庭园艺肥料和杀虫剂。药物和酒精使用、感染和肝脏疾病的评估均为阴性。尽管进行了积极的治疗，但血液中NH3浓度达到峰值2050 μM，患者死于脑水肿和小脑疝。OTC基因的分析显示，在第7外显子上有一个Pro-225-Thr （P225T）的变化，这个突变先前与OTC缺乏症有关。本病例表明，OTC缺乏症可导致先前健康成人急性严重高氨血症，P225T突变可与迟发性OTC缺乏症相关。我们推测，接触有机化学品可能是导致该患者出现症状的原因。本病例还强调，持续的高氨血症可能导致不可逆的神经损伤，在急性患者确诊为高氨血症后，应进行某些诊断试验，以区分尿素循环障碍和高氨血症脑病的其他原因。
Ornithine transcarbamylase (OTC) deficiency is an X-linked urea cycle defect. While hemizygous males typically present with hyperammonemic coma in infancy, reports of rare late-onset presentations exist, with poor outcomes in males up to 58 years old. Relatives with mutations identical to affected patients often remain asymptomatic, and it is likely that environmental and genetic factors influence disease penetrance and expression. Here, we present our investigation of a patient with late-onset presentation, and we emphasize the potential role of environmental and genetic factors on disease expression. The patient was a previously healthy 62-year-old man who developed mental slowing, refractory seizures, and coma over an 8-day period. Interestingly, the patient had recently used home gardening fertilizers and pesticides. Evaluations for drug and alcohol use, infections, and liver disease were negative. Despite aggressive therapy, blood NH3 concentration peaked at 2,050 μM and the patient died from cerebral edema and cerebellar herniation. Analysis of the OTC gene showed a Pro-225-Thr (P225T) change in exon 7, a mutation that has been previously implicated in OTC deficiency. This case illustrates that OTC deficiency can cause acute, severe hyperammonemia in a previously healthy adult and that the P225T mutation can be associated with late-onset OTC deficiency. We speculate that exposure to organic chemicals might have contributed to the onset of symptoms in this patient. This case also emphasizes that persistent hyperammonemia may cause irreversible neurologic damage and that after the diagnosis of hyperammonemia is established in an acutely ill patient, certain diagnostic tests should be performed to differentiate between urea cycle disorders and other causes of hyperammonemic encephalopathy.
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影响因子：
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通讯作者：
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