NEUROLOGIC CRISES IN HEREDITARY TYROSINEMIA
NEUROLOGIC CRISES IN HEREDITARY TYROSINEMIA
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DOI：
10.1056/nejm199002153220704
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发表时间：
1990-02-15
影响因子：
158.5
通讯作者：
DALLAIRE, L
中科院分区：
文献类型：
--
作者：
MITCHELL, G;LAROCHELLE, J;DALLAIRE, L
遗传性酪氨酸血症是由于酪氨酸代谢最后一步的先天性错误。已知该疾病可引起急性和慢性肝功能衰竭、肾Fanconi综合征和肝细胞癌。神经系统的表现已被报道，但没有强调作为一个共同的问题。在本文中，我们描述了自1970年以来，在新生儿筛查中被确定为患有酪氨酸血症的儿童中发生的神经系统危机。在48名患有酪氨酸血症的儿童中，有20名（42%）在平均一岁时开始出现神经系统危机，导致104人住院。这些周围神经病变的突然发作的特征是严重的疼痛与伸肌张力亢进（75%），呕吐或麻痹性肠梗阻（69%），肌肉无力（29%），和自残（8%）。8名儿童因瘫痪需要机械通气，20名儿童中有14人死亡。在危机之间，大多数幸存者恢复了正常功能。我们没有发现危象的可靠生化标志物（我们评估的指标包括酪氨酸、琥珀酰丙酮和肝转氨酶的血液水平）。δ-的尿排泄氨基乙酰丙酸是卟啉生物合成的神经毒性中间体，在危象期间以及在无症状期间升高。7例患者的电生理检查和3例患者的神经肌肉活检显示轴突变性和继发性脱髓鞘。我们的结论是，发作急性，严重的周围神经病变是常见的遗传性酪氨酸血症和类似的危机，神经性卟啉症。
Hereditary tyrosinemia results from an inborn error in the final step of tyrosine metabolism. The disease is known to cause acute and chronic liver failure, renal Fanconi''s syndrome, and hepatocellular carcinoma. Neurologic manifestations have been reported but not emphasized as a common problem. In this paper, we describe neurologic crises that occurred among children identified as having tyrosinemia on neonatal screening since 1970. Of the 48 children with tyrosinemia, 20 (42 percent) had neurologic crises that began at a mean age of one year and led to 104 hospital admissions. These abrupt episodes of peripheral neuropathy were characterized by severe pain with extensor hypertonia (in 75 percent), vomiting or paralytic ileus (69 percent), muscle weakness (29 percent), and self-mutilation (8 percent). Eight children required mechanical ventilation because of paralysis, and 14 of the 20 children have died. Between crises, most survivors regained normal function. We found no reliable biochemical marker for the crises (those we evaluated included blood levels of tyrosine, succinylacetone, and hepatic aminotransferases). Urinary excretion of .delta.-aminolevulinic acid, a neurotoxic intermediate of porphyrin biosynthesis, was elevated during crises but also during the asymptomatic periods. Electrophysiologic studies in seven patients and neuromuscular biopsies in three patients showed axonal degeneration and secondary demyelination. We conclude that episodes of acute, severe peripheral neuropathy are common in hereditary tyrosinemia and resemble the crises of neuropathic porphyrias.